2,412
Views
0
CrossRef citations to date
0
Altmetric
Review

Absorption, Distribution, Metabolism and Excretion Pharmacogenomics of Drugs of Abuse

&
Pages 215-233 | Published online: 18 Feb 2011

Bibliography

  • Daly AK : Pharmacogenetics and human genetic polymorphisms.Biochem. J.429 , 435–449 (2010).
  • Hesselink DA , BouamarR, van Gelder T: The pharmacogenetics of calcineurin inhibitor-related nephrotoxicity. Ther. Drug Monit.32(4) , 387–393 (2010).
  • Sheehan JJ , SliwaJK, AmatniekJC, GrinspanA, CanusoCM: Atypical antipsychotic metabolism and excretion.Curr. Drug Metab.11 , 516–525 (2010).
  • Ciarimboli G : Organic cation transporters.Xenobiotica38 , 936–971 (2008).
  • Eichelbaum M , Ingelman-SundbergM, EvansWE: Pharmacogenomics and individualized drug therapy.Annu. Rev. Med.57 , 119–137 (2006).
  • Shah RR : Can pharmacogenetics help rescue drugs withdrawn from the market?Pharmacogenomics7 , 889–908 (2006).
  • Zhang ZY , WongYN: Enzyme kinetics for clinically relevant CYP inhibition.Curr. Drug Metab.6 , 241–257 (2005).
  • Tang C , LinJH, LuAY: Metabolism-based drug–drug interactions: what determines individual variability in cytochrome P450 induction?Drug Metab. Dispos.33 , 603–613 (2005).
  • Lotsch J , SkarkeC, LiefholdJ, GeisslingerG: Genetic predictors of the clinical response to opioid analgesics: clinical utility and future perspectives.Clin. Pharmacokinet.43 , 983–1013 (2004).
  • Zanger UM , RaimundoS, EichelbaumM: Cytochrome P450 2D6: overview and update on pharmacology, genetics, biochemistry.Naunyn Schmiedebergs Arch. Pharmacol.369 , 23–37 (2004).
  • Evans WE , McLeodHL: Pharmacogenomics-drug disposition, drug targets, and side effects.N. Engl. J. Med.348 , 538–549 (2003).
  • Pritzker D , KanungoA, KilicarslanT, TyndaleRF, SellersEM: Designer drugs that are potent inhibitors of CYP2D6.J. Clin. Psychopharmacol.22 , 330–332 (2002).
  • Antoniou T , TsengAL: Interactions between recreational drugs and antiretroviral agents.Ann. Pharmacother.36 , 1598–1613 (2002).
  • Rendic S : Summary of information on human CYP enzymes: human P450 metabolism data.Drug Metab. Rev.34 , 83–448 (2002).
  • Howard LA , SellersEM, TyndaleRF: The role of pharmacogenetically-variable cytochrome P450 enzymes in drug abuse and dependence.Pharmacogenomics3 , 185–199 (2002).
  • Ingelman-Sundberg M : Polymorphism of cytochrome P450 and xenobiotic toxicity.Toxicology181–182, 447–452 (2002).
  • Zhou SF , LiuJP, ChowbayB: Polymorphism of human cytochrome P450 enzymes and its clinical impact.Drug Metab. Rev.41 , 89–295 (2009).
  • Zhou SF : Polymorphism of human cytochrome P450 2D6 and its clinical significance: part II.Clin. Pharmacokinet.48 , 761–804 (2009).
  • Suzuki Y , SugaiT, FukuiN et al.: CYP2D6 genotype and smoking influence fluvoxamine steady-state concentration in Japanese psychiatric patients: lessons for genotype–phenotype association study design in translational pharmacogenetics.J. Psychopharmacol. (2010) (Epub ahead of print).
  • Chan WH , ChenTL, ChenRM, SunWZ, UengTH: Propofol metabolism is enhanced after repetitive ketamine administration in rats: the role of cytochrome P-450 2B induction.Br. J. Anaesth.97 , 351–358 (2006).
  • Wojnowski L : Genetics of the variable expression of CYP3A in humans.Ther. Drug Monit.26 , 192–199 (2004).
  • Gibson GG , PlantNJ, SwalesKE, AyrtonA, El Sankary W: Receptor-dependent transcriptional activation of cytochrome P4503A genes: induction mechanisms, species differences and interindividual variation in man. Xenobiotica32 , 165–206 (2002).
  • Evans AM : Influence of dietary components on the gastrointestinal metabolism and transport of drugs.Ther. Drug Monit.22 , 131–136 (2000).
  • Ozdemir V , KalowaW, TangBK et al.: Evaluation of the genetic component of variability in CYP3A4 activity: a repeated drug administration method.Pharmacogenetics10 , 373–388 (2000).
  • Crettol S , PetrovicN, MurrayM: Pharmacogenetics of phase I and phase II drug metabolism.Curr. Pharm. Des.16 , 204–219 (2010).
  • Hayes JD , StrangeRC: Glutathione S-transferase polymorphisms and their biological consequences.Pharmacology61 , 154–166 (2000).
  • Staatz CE , GoodmanLK, TettSE: Effect of CYP3A and ABCB1 single nucleotide polymorphisms on the pharmacokinetics and pharmacodynamics of calcineurin inhibitors: part II.Clin. Pharmacokinet.49 , 207–221 (2010).
  • Maurer HH , SauerC, TheobaldDS: Toxicokinetics of drugs of abuse: current knowledge of the isoenzymes involved in the human metabolism of tetrahydrocannabinol, cocaine, heroin, morphine, and codeine.Ther. Drug Monit.28 , 447–453 (2006).
  • Kraemer T , MaurerHH: Toxicokinetics of amphetamines: metabolism and toxicokinetic data of designer drugs, of amphetamine, methamphetamine and their N-alkyl derivatives.Ther. Drug Monit.24 , 277–289 (2002).
  • Staack RF , MaurerHH: Metabolism of designer drugs of abuse.Curr. Drug Metab.6 , 259–274 (2005).
  • Meyer MR , MaurerHH: Metabolism of designer drugs of abuse: an updated review.Curr. Drug Metab.11 , 468–482 (2010).
  • Vandevenne M , VandenbusscheH, VerstraeteA: Detection time of drugs of abuse in urine.Acta Clin. Belg.55 , 323–333 (2000).
  • Verstraete AG : Detection times of drugs of abuse in blood, urine, and oral fluid.Ther. Drug Monit.26 , 200–205 (2004).
  • Maurer HH : Position of chromatographic techniques in screening for detection of drugs or poisons in clinical and forensic toxicology and/or doping control.Clin. Chem. Lab. Med.42 , 1310–1324 (2004).
  • Maurer HH : The relevance of pharmacogenetics and of metabolic interactions for clinical and forensic toxicology. In: Proceedings of the XIIIth GTFCh Symposium in Mosbach. Pragst F, Aderjan R (Eds). Helm-Verlag, Heppenheim, Germany, 197–203 (2003).
  • Maurer HH : Toxicokinetics – variations due to genetics or interactions: basics and examples. In: Current Contributions to Forensic and Clinical Toxicology. Pragst F, Aderjan R (Eds). GTFCH, Bad Vilbel, Germany, 153–155 (2008).
  • Smith HS : Opioid metabolism.Mayo Clin. Proc.84 , 613–624 (2009).
  • Stamer UM , ZhangL, StuberF: Personalized therapy in pain management: where do we stand?Pharmacogenomics11 , 843–864 (2010).
  • Gilson AM , KreisPG: The burden of the nonmedical use of prescription opioid analgesics.Pain Med.10(Suppl. 2) , S89–S100 (2009).
  • Yamamoto Y , SmithRR, BernankeDH: Accelerated nonmuscle contraction after subarachnoid hemorrhage: culture and characterization of myofibroblasts from human cerebral arteries in vasospasm.Neurosurgery30 , 337–345 (1992).
  • Kalso E : Oxycodone.J. Pain Symptom. Manage.29 , S47–S56 (2005).
  • Lalovic B , PhillipsB, RislerLL, HowaldW, ShenDD: Quantitative contribution of CYP2D6 and CYP3A to oxycodone metabolism in human liver and intestinal microsomes.Drug Metab. Dispos.32 , 447–454 (2004).
  • Nieminen TH , HagelbergNM, SaariTI et al.: Rifampin greatly reduces the plasma concentrations of intravenous and oral oxycodone.Anesthesiology110 , 1371–1378 (2009).
  • Samer CF , DaaliY, WagnerM et al.: Genetic polymorphisms and drug interactions modulating CYP2D6 and CYP3A activities have a major effect on oxycodone analgesic efficacy and safety.Br. J. Pharmacol.160 , 919–930 (2010).
  • Lee HK , LewisLD, TsongalisGJ et al.: Negative urine opioid screening caused by rifampin-mediated induction of oxycodone hepatic metabolism.Clin. Chim. Acta367 , 196–200 (2006).
  • Sasaki T , EkinoS, YonemasuK: Effect of bursectomy on serum levels of chicken complement component C1q.Dev. Comp. Immunol.16 , 257–261 (1992).
  • Otton SV , SchadelM, CheungSW et al.: CYP2D6 phenotype determines the metabolic conversion of hydrocodone to hydromorphone.Clin. Pharmacol. Ther.54 , 463–472 (1993).
  • Sullivan HR , DueSL: Urinary metabolites of dl-methadone in maintenance subjects.J. Med. Chem.16 , 909–913 (1973).
  • Eap CB , BuclinT, BaumannP: Interindividual variability of the clinical pharmacokinetics of methadone: implications for the treatment of opioid dependence.Clin. Pharmacokinet.41 , 1153–1193 (2002).
  • Crettol S , DeglonJJ, BessonJ et al.: ABCB1 and cytochrome P450 genotypes and phenotypes: influence on methadone plasma levels and response to treatment.Clin. Pharmacol. Ther.80 , 668–681 (2006).
  • Wang H , TompkinsLM: CYP2B6: new insights into a historically overlooked cytochrome P450 isozyme.Curr. Drug Metab.9 , 598–610 (2008).
  • Zanger UM , KleinK, SausseleT et al.: Polymorphic CYP2B6: molecular mechanisms and emerging clinical significance.Pharmacogenomics8 , 743–759 (2007).
  • Totah RA , SheffelsP, RobertsT et al.: Role of CYP2B6 in stereoselective human methadone metabolism.Anesthesiology108 , 363–374 (2008).
  • Li Y , KantelipJP, Gerritsen-van Schieveen P, Davani S: Interindividual variability of methadone response: impact of genetic polymorphism. Mol. Diagn. Ther.12 , 109–124 (2008).
  • Finch JS , DeKornfeldTJ: Clinical investigation of the analgesic potency and respiratory depressant activity of fentanyl, a new narcotic analgesic.J. Clin. Pharmacol. J. New Drugs7 , 46–51 (1967).
  • Labroo RB , PaineMF, ThummelKE, KharaschED: Fentanyl metabolism by human hepatic and intestinal cytochrome P450 3A4: implications for interindividual variability in disposition, efficacy, and drug interactions.Drug Metab. Dispos.25 , 1072–1080 (1997).
  • Silverstein JH , RiedersMF, McMullinM, SchulmanS, ZahlK: An analysis of the duration of fentanyl and its metabolites in urine and saliva.Anesth. Analg.76 , 618–621 (1993).
  • Tateishi T , KrivorukY, UengYF et al.: Identification of human liver cytochrome P-450 3A4 as the enzyme responsible for fentanyl and sufentanil N-dealkylation.Anesth. Analg.82 , 167–172 (1996).
  • Feierman DE , LaskerJM: Metabolism of fentanyl, a synthetic opioid analgesic, by human liver microsomes. Role of CYP3A4.Drug Metab. Dispos.24 , 932–939 (1996).
  • Park HJ , ShinnHK, RyuSH et al.: Genetic polymorphisms in the ABCB1 gene and the effects of fentanyl in Koreans.Clin. Pharmacol. Ther.81 , 539–546 (2007).
  • Henthorn TK , LiuY, MahapatroM, NgKY: Active transport of fentanyl by the blood–brain barrier.J. Pharmacol. Exp. Ther.289 , 1084–1089 (1999).
  • Elkiweri IA , ZhangYL, ChristiansU et al.: Competitive substrates for P-glycoprotein and organic anion protein transporters differentially reduce blood organ transport of fentanyl and loperamide: pharmacokinetics and pharmacodynamics in Sprague-Dawley rats.Anesth. Analg.108 , 149–159 (2009).
  • Huang P , KehnerGB, CowanA, Liu-ChenLY: Comparison of pharmacological activities of buprenorphine and norbuprenorphine: norbuprenorphine is a potent opioid agonist.J. Pharmacol. Exp. Ther.297 , 688–695 (2001).
  • Iribarne C , PicartD, DreanoY, BailJP, BerthouF: Involvement of cytochrome P450 3A4 in N-dealkylation of buprenorphine in human liver microsomes.Life Sci.60 , 1953–1964 (1997).
  • Kobayashi K , YamamotoT, ChibaK et al.: Human buprenorphine N-dealkylation is catalyzed by cytochrome P450 3A4.Drug Metab. Dispos.26 , 818–821 (1998).
  • Picard N , CresteilT, DjebliN, MarquetP: In vitro metabolism study of buprenorphine: evidence for new metabolic pathways.Drug Metab. Dispos.33 , 689–695 (2005).
  • Bruce RD , McCance-KatzE, KharaschED, MoodyDE, MorseGD: Pharmacokinetic interactions between buprenorphine and antiretroviral medications.Clin. Infect. Dis.43(Suppl. 4) , S216–S223 (2006).
  • McCance-Katz EF , MoodyDE, MorseGD et al.: Interaction between buprenorphine and atazanavir or atazanavir/ritonavir.Drug Alcohol Depend.91 , 269–278 (2007).
  • Cone EJ , GorodetzkyCW, YousefnejadD, BuchwaldWF, JohnsonRE: The metabolism and excretion of buprenorphine in humans.Drug Metab. Dispos.12 , 577–581 (1984).
  • King CD , GreenMD, RiosGR et al.: The glucuronidation of exogenous and endogenous compounds by stably expressed rat and human UDP-glucuronosyltransferase 1.1.Arch. Biochem. Biophys.332 , 92–100 (1996).
  • Chang Y , MoodyDE: Glucuronidation of buprenorphine and norbuprenorphine by human liver microsomes and UDP-glucuronosyltransferases.Drug Metab. Lett.3 , 101–107 (2009).
  • Green MD , KingCD, MojarrabiB, MackenziePI, TephlyTR: Glucuronidation of amines and other xenobiotics catalyzed by expressed human UDP-glucuronosyltransferase 1A3.Drug Metab. Dispos.26 , 507–512 (1998).
  • Rios GR , TephlyTR: Inhibition and active sites of UDP-glucuronosyltransferases 2B7 and 1A1.Drug Metab. Dispos.30 , 1364–1367 (2002).
  • Rouguieg K , PicardN, SauvageFL, GaulierJM, MarquetP: Contribution of the different UDP-glucuronosyltransferase (UGT) isoforms to buprenorphine and norbuprenorphine metabolism and relationship with the main UGT polymorphisms in a bank of human liver microsomes.Drug Metab. Dispos.38 , 40–45 (2010).
  • Driessen B , ReimannW, GiertzH: Effects of the central analgesic tramadol on the uptake and release of noradrenaline and dopamine in vitro.Br. J. Pharmacol.108 , 806–811 (1993).
  • Driessen B , ReimannW: Interaction of the central analgesic, tramadol, with the uptake and release of 5-hydroxytryptamine in the rat brain in vitro.Br. J. Pharmacol.105 , 147–151 (1992).
  • Gillen C , HaurandM, KobeltDJ, WnendtS: Affinity, potency and efficacy of tramadol and its metabolites at the cloned human µ-opioid receptor.Naunyn Schmiedebergs Arch. Pharmacol.362 , 116–121 (2000).
  • Subrahmanyam V , RenwickAB, WaltersDG et al.: Identification of cytochrome P-450 isoforms responsible for cis-tramadol metabolism in human liver microsomes.Drug Metab. Dispos.29 , 1146–1155 (2001).
  • Pedersen RS , DamkierP, BrosenK: Enantioselective pharmacokinetics of tramadol in CYP2D6 extensive and poor metabolizers.Eur. J. Clin. Pharmacol.62 , 513–521 (2006).
  • Stamer UM , MusshoffF, KobilayM et al.: Concentrations of tramadol and O-desmethyltramadol enantiomers in different CYP2D6 genotypes.Clin. Pharmacol. Ther.82 , 41–47 (2007).
  • Kreek MJ , BartG, LillyC, LaForgeKS, NielsenDA: Pharmacogenetics and human molecular genetics of opiate and cocaine addictions and their treatments.Pharmacol. Rev.57 , 1–26 (2005).
  • Kamendulis LM , BrzezinskiMR, PindelEV, BosronWF, DeanRA: Metabolism of cocaine and heroin is catalyzed by the same human liver carboxylesterases.J. Pharmacol. Exp. Ther.279 , 713–717 (1996).
  • Bencharit S , MortonCL, XueY, PotterPM, RedinboMR: Structural basis of heroin and cocaine metabolism by a promiscuous human drug-processing enzyme.Nat. Struct. Biol.10 , 349–356 (2003).
  • Brzezinski MR , SpinkBJ, DeanRA et al.: Human liver carboxylesterase hCE-1: binding specificity for cocaine, heroin, and their metabolites and analogs.Drug Metab. Dispos.25 , 1089–1096 (1997).
  • Kilpatrick GJ , SmithTW: Morphine-6-glucuronide: actions and mechanisms.Med. Res. Rev.25 , 521–544 (2005).
  • Stone AN , MackenziePI, GaletinA, HoustonJB, MinersJO: Isoform selectivity and kinetics of morphine 3- and 6-glucuronidation by human UDP-glucuronosyltransferases: evidence for atypical glucuronidation kinetics by UGT2B7.Drug Metab. Dispos.31 , 1086–1089 (2003).
  • Projean D , MorinPE, TuTM, DucharmeJ: Identification of CYP3A4 and CYP2C8 as the major cytochrome P450 s responsible for morphine N-demethylation in human liver microsomes.Xenobiotica33 , 841–854 (2003).
  • Skarke C , SchmidtH, GeisslingerG, DarimontJ, LotschJ: Pharmacokinetics of morphine are not altered in subjects with Gilbert‘s syndrome.Br. J. Clin. Pharmacol.56 , 228–231 (2003).
  • Fujita KI , AndoY, YamamotoW et al.: Association of UGT2B7 and ABCB1 genotypes with morphine-induced adverse drug reactions in Japanese patients with cancer.Cancer Chemother. Pharmacol. (2009) (Epub ahead of print).
  • Sindrup SH , BrosenK, BjerringP et al.: Codeine increases pain thresholds to copper vapor laser stimuli in extensive but not poor metabolizers of sparteine.Clin. Pharmacol. Ther.48 , 686–693 (1990).
  • Yue QY , AlmC, SvenssonJO, SaweJ: Quantification of the O- and N-demethylated and the glucuronidated metabolites of codeine relative to the debrisoquine metabolic ratio in urine in ultrarapid, rapid, and poor debrisoquine hydroxylators.Ther. Drug Monit.19 , 539–542 (1997).
  • Kathiramalainathan K , KaplanHL, RomachMK et al.: Inhibition of cytochrome P450 2D6 modifies codeine abuse liability.J. Clin. Psychopharmacol.20 , 435–444 (2000).
  • Yue QY , SaweJ: Different effects of inhibitors on the O- and N-demethylation of codeine in human liver microsomes.Eur. J. Clin. Pharmacol.52 , 41–47 (1997).
  • Caraco Y , TateishiT, GuengerichFP, WoodAJ: Microsomal codeine N-demethylation: cosegregation with cytochrome P4503A4 activity.Drug Metab. Dispos.24 , 761–764 (1996).
  • Court MH , KrishnaswamyS, HaoQ et al.: Evaluation of 3´-azido-3´-deoxythymidine, morphine, and codeine as probe substrates for UDP-glucuronosyltransferase 2B7 (UGT2B7) in human liver microsomes: specificity and influence of the UGT2B7*2 polymorphism.Drug Metab. Dispos.31 , 1125–1133 (2003).
  • Madadi P , RossCJ, HaydenMR et al.: Pharmacogenetics of neonatal opioid toxicity following maternal use of codeine during breastfeeding: a case–control study.Clin. Pharmacol. Ther.85 , 31–35 (2009).
  • Gasche Y , DaaliY, FathiM et al.: Codeine intoxication associated with ultrarapid CYP2D6 metabolism.N. Engl. J. Med.351 , 2827–2831 (2004).
  • Nicholson KL , BalsterRL: GHB: a new and novel drug of abuse.Drug Alcohol Depend.63 , 1–22 (2001).
  • Kugelberg FC , HolmgrenA, EklundA, JonesAW: Forensic toxicology findings in deaths involving γ-hydroxybutyrate.Int. J. Legal Med.124 , 1–6 (2010).
  • Kuiper MA , PeikertN, BoermaEC: γ-hydroxybutyrate withdrawal syndrome: a case report.Cases J.2 , 6530 (2009).
  • Tarabar AF , NelsonLS: The γ-hydroxybutyrate withdrawal syndrome.Toxicol. Rev.23 , 45–49 (2004).
  • van Noorden MS , van Dongen LC, Zitman FG, Vergouwen TA: γ-hydroxybutyrate withdrawal syndrome: dangerous but not well-known. Gen. Hosp. Psychiatry31 , 394–396 (2009).
  • Lyon RC , JohnstonSM, PanopoulosA et al.: Enzymes involved in the metabolism of γ-hydroxybutyrate in SH-SY5Y cells: identification of an iron-dependent alcohol dehydrogenase ADHFe1.Chem. Biol. Interact.178 , 283–287 (2009).
  • Bessman SP , FishbeinWN: γ-hydroxybutyrate, a normal brain metabolite.Nature200 , 1207–1208 (1963).
  • Drasbek KR , ChristensenJ, JensenK: γ-hydroxybutyrate – a drug of abuse.Acta Neurol. Scand.114 , 145–156 (2006).
  • Vayer P , MandelP, MaitreM: Conversion of γ-hydroxybutyrate to γ-aminobutyrate in vitro.J. Neurochem.45 , 810–814 (1985).
  • Park J , OseiYD, ChurchichJE: Isolation and characterization of recombinant mitochondrial 4-aminobutyrate aminotransferase.J. Biol. Chem.268 , 7636–7639 (1993).
  • O‘Connor T , IrelandLS, HarrisonDJ, HayesJD: Major differences exist in the function and tissue-specific expression of human aflatoxin B1 aldehyde reductase and the principal human aldo-keto reductase AKR1 family members.Biochem. J.343(Pt 2) , 487–504 (1999).
  • York JL , GrollmanAP, BublitzC: TPN-L-gluonate dehydrogenase.Biochim. Biophys. Acta47 , 298–306 (1961).
  • Vayer P , SchmittM, BourguignonJJ, MandelP, MaitreM: Evidence for a role of high Km aldehyde reductase in the degradation of endogenous γ-hydroxybutyrate from rat brain.FEBS Lett.190 , 55–60 (1985).
  • Kaufman EE , NelsonT, FalesHM, LevinDM: Isolation and characterization of a hydroxyacid-oxoacid transhydrogenase from rat kidney mitochondria.J. Biol. Chem.263 , 16872–16879 (1988).
  • Struys EA , VerhoevenNM, Ten Brink HJ et al.: Kinetic characterization of human hydroxyacid-oxoacid transhydrogenase: relevance to D-2-hydroxyglutaric and γ-hydroxybutyric acidurias. J. Inherit. Metab. Dis.28 , 921–930 (2005).
  • Kaufman EE , NelsonT: An overview of γ-hydroxybutyrate catabolism: the role of the cytosolic NADP(+)-dependent oxidoreductase EC 1.1.1.19 and of a mitochondrial hydroxyacid-oxoacid transhydrogenase in the initial, rate-limiting step in this pathway.Neurochem. Res.16 , 965–974 (1991).
  • Gibson KM , HoffmannGF, HodsonAK, BottiglieriT, JakobsC: 4-Hydroxybutyric acid and the clinical phenotype of succinic semialdehyde dehydrogenase deficiency, an inborn error of GABA metabolism.Neuropediatrics29 , 14–22 (1998).
  • Andresen H , SprysN, SchmoldtA, MuellerA, Iwersen-BergmannS: γ-hydroxybutyrate in urine and serum: additional data supporting current cut-off recommendations.Forensic Sci. Int.200 , 93–99 (2010).
  • Wilson C , CanningP, CaravatiEM: The abuse potential of propofol.Clin. Toxicol. (Phila.)48 , 165–170 (2010).
  • Hetz G : [How expensive must a treatment room be?].Zahnarztl. Prax.42 , 91–92 (1991).
  • Simons PJ , CockshottID, DouglasEJ et al.: Species differences in blood profiles, metabolism and excretion of 14C-propofol after intravenous dosing to rat, dog and rabbit.Xenobiotica21 , 1243–1256 (1991).
  • Sneyd JR , SimonsPJ, WrightB: Use of proton NMR spectroscopy to measure propofol metabolites in the urine of the female Caucasian patient.Xenobiotica24 , 1021–1028 (1994).
  • Yamazaki H , ShimizuM, NagashimaT, MinoshimaM, MurayamaN: Rat cytochrome P450 2C11 in liver microsomes involved in oxidation of anesthetic agent propofol and deactivated by prior treatment with propofol.Drug Metab. Dispos.34 , 1803–1805 (2006).
  • Donato MT , MonteroS, CastellJV, Gomez-LechonMJ, LahozA: Validated assay for studying activity profiles of human liver UGTs after drug exposure: inhibition and induction studies.Anal. Bioanal. Chem.396 , 2251–2263 (2010).
  • Fujiwara R , NakajimaM, YamanakaH et al.: Effects of coexpression of UGT1A9 on enzymatic activities of human UGT1A isoforms.Drug Metab. Dispos.35 , 747–757 (2007).
  • Court MH , DuanSX, HesseLM, VenkatakrishnanK, GreenblattDJ: Cytochrome P-450 2B6 is responsible for interindividual variability of propofol hydroxylation by human liver microsomes.Anesthesiology94 , 110–119 (2001).
  • Murayama N , MinoshimaM, ShimizuM, GuengerichFP, YamazakiH: Involvement of human cytochrome P450 2B6 in the ω- and 4-hydroxylation of the anesthetic agent propofol.Xenobiotica37 , 717–724 (2007).
  • Oda Y , HamaokaN, HiroiT et al.: Involvement of human liver cytochrome P4502B6 in the metabolism of propofol.Br. J. Clin. Pharmacol.51 , 281–285 (2001).
  • Favetta P , DegouteCS, PerdrixJP et al.: Propofol metabolites in man following propofol induction and maintenance.Br. J. Anaesth.88 , 653–658 (2002).
  • Takahashi H , MaruoY, MoriA et al.: Effect of D256N and Y483D on propofol glucuronidation by human uridine 5´-diphosphate glucuronosyltransferase (UGT1A9).Basic Clin. Pharmacol. Toxicol.103 , 131–136 (2008).
  • Rang HP , DaleMM, RitterJM: Pharmacology, 6th Edition. Churchill Livingston, London, UK, 532–533 (2007).
  • Hirota K , LambertDG: Ketamine: its mechanism(s) of action and unusual clinical uses.Br. J. Anaesth.77 , 441–444 (1996).
  • Anis NA , BerrySC, BurtonNR, LodgeD: The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N-methyl-aspartate.Br. J. Pharmacol.79 , 565–575 (1983).
  • Gill PA : Non-medical use of ketamine.BMJ306 , 1340 (1993).
  • Pal HR , BerryN, KumarR, RayR: Ketamine dependence.Anaesth. Intensive Care30 , 382–384 (2002).
  • Curran HV , MorganC: Cognitive, dissociative and psychotogenic effects of ketamine in recreational users on the night of drug use and 3 days later.Addiction95 , 575–590 (2000).
  • Curran HV , MonaghanL: In and out of the K-hole: a comparison of the acute and residual effects of ketamine in frequent and infrequent ketamine users.Addiction96 , 749–760 (2001).
  • Wang YC , ChenSK, LinCM: Breaking the drug addiction cycle is not easy in ketamine abusers.Int. J. Urol.17 , 496 (2010).
  • Adams JD Jr, Baillie TA, Trevor AJ, Castagnoli N Jr: Studies on the biotransformation of ketamine. 1-Identification of metabolites produced in vitro from rat liver microsomal preparations. Biomed. Mass Spectrom.8 , 527–538 (1981).
  • Chang T , GlazkoAJ: Biotransformation and disposition of ketamine.Int. Anesthesiol. Clin.12 , 157–177 (1974).
  • Turfus SC , ParkinMC, CowanDA et al.: Use of human microsomes and deuterated substrates: an alternative approach for the identification of novel metabolites of ketamine by mass spectrometry.Drug Metab. Dispos.37 , 1769–1778 (2009).
  • Adamowicz P , KalaM: Urinary excretion rates of ketamine and norketamine following therapeutic ketamine administration: method and detection window considerations.J. Anal. Toxicol.29 , 376–382 (2005).
  • Cheng PS , FuCY, LeeCH, LiuC, ChienCS: GC-MS quantification of ketamine, norketamine, and dehydronorketamine in urine specimens and comparative study using ELISA as the preliminary test methodology.J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.852 , 443–449 (2007).
  • Yanagihara Y , KariyaS, OhtaniM et al.: Involvement of CYP2B6 in N-demethylation of ketamine in human liver microsomes.Drug Metab. Dispos.29 , 887–890 (2001).
  • Hijazi Y , BoulieuR: Contribution of CYP3A4, CYP2B6, and CYP2C9 isoforms to N-demethylation of ketamine in human liver microsomes.Drug Metab. Dispos.30 , 853–858 (2002).
  • Persson J , HasselstromJ, MaursetA et al.: Pharmacokinetics and non-analgesic effects of S- and R-ketamines in healthy volunteers with normal and reduced metabolic capacity.Eur. J. Clin. Pharmacol.57 , 869–875 (2002).
  • Isaacs SO , MartinP, WashingtonJA Jr: Phencyclidine (PCP) abuse. A close-up look at a growing problem. Oral Surg. Oral Med. Oral Pathol.61 , 126–129 (1986).
  • Sauer C , PetersFT, StaackRF, FritschiG, MaurerHH: Metabolism and toxicological detection of a new designer drug, N-(1-phenylcyclohexyl)propanamine, in rat urine using gas chromatography-mass spectrometry.J. Chromatogr. A1186 , 380–390 (2008).
  • Sauer C , PetersFT, StaackRF, FritschiG, MaurerHH: Metabolism and toxicological detection of the designer drug N-(1-phenylcyclohexyl)-3-methoxypropanamine (PCMPA) in rat urine using gas chromatography-mass spectrometry.Forensic Sci. Int.181 , 47–51 (2008).
  • Sauer C , PetersFT, StaackRF, FritschiG, MaurerHH: New designer drug (1-(1-phenylcyclohexyl)-3-ethoxypropylamine (PCEPA): studies on its metabolism and toxicological detection in rat urine using gas chromatography/mass spectrometry.J. Mass Spectrom.41 , 1014–1029 (2006).
  • Sauer C , PetersFT, StaackRF, FritschiG, MaurerHH: New designer drugs N-(1-phenylcyclohexyl)-2-ethoxyethanamine (PCEEA) and N-(1-phenylcyclohexyl)-2-methoxyethanamine (PCMEA): studies on their metabolism and toxicological detection in rat urine using gas chromatographic/mass spectrometric techniques.J. Mass Spectrom.43 , 305–316 (2008).
  • Takeda H , GazzaraRA, HowardSG: Phenylcyclohexylamine: effect of a metabolite of phencyclidine on the efflux of dopamine in the rat.Neuropharmacology25 , 1341–1345 (1986).
  • Cook CE , BrineDR, QuinGD, Perez-ReyesM, Di Guiseppi SR: Phencyclidine and phenylcyclohexene disposition after smoking phencyclidine. Clin. Pharmacol. Ther.31 , 635–641 (1982).
  • Cook CE , BrineDR, JeffcoatAR et al.: Phencyclidine disposition after intravenous and oral doses.Clin. Pharmacol. Ther.31 , 625–634 (1982).
  • Laurenzana EM , OwensSM: Metabolism of phencyclidine by human liver microsomes.Drug Metab. Dispos.25 , 557–563 (1997).
  • Cook CE , JeffcoatAR, Perez-ReyesM: Pharmacokinetic studies of cocaine and phencyclidine in man. In: Pharmacokinetics and Pharmacodynamics of Psychoactive Drugs. Barnett G, Chiang CN (Eds). Biomedical Publications, Forest City, CA, USA, 48–74 (1985).
  • Jushchyshyn MI , KentUM, HollenbergPF: The mechanism-based inactivation of human cytochrome P450 2B6 by phencyclidine.Drug Metab. Dispos.31 , 46–52 (2003).
  • Sauer C , PetersFT, SchwaningerAE, MeyerMR, MaurerHH: Identification of cytochrome P450 enzymes involved in the metabolism of the designer drugs N-(1-phenylcyclohexyl)-3-ethoxypropanamine (PCEPA) and N-(1-phenylcyclohexyl)-3-methoxypropanamine (PCMPA).Chem. Res. Toxicol.21 , 1949–1955 (2008).
  • Sauer C , PetersFT, SchwaningerAE, MeyerMR, MaurerHH: Investigations on the cytochrome P450 (CYP) isoenzymes involved in the metabolism of the designer drugs N-(1-phenylcyclohexyl)-2-ethoxyethanamine and N-(1-phenylcyclohexyl)-2-methoxyethanamine.Biochem. Pharmacol.77 , 444–450 (2009).
  • Shimada T , YamazakiH, MimuraM, InuiY, GuengerichFP: Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians.J. Pharmacol. Exp. Ther.270 , 414–423 (1994).
  • de Jongh R , BoltI, SchermerM, OlivierB: Botox for the brain: enhancement of cognition, mood and pro-social behavior and blunting of unwanted memories.Neurosci. Biobehav. Rev.32 , 760–776 (2008).
  • Sahakian B , Morein-ZamirS: Professor‘s little helper.Nature450 , 1157–1159 (2007).
  • Solanto MV : Neuropsychopharmacological mechanisms of stimulant drug action in attention-deficit hyperactivity disorder: a review and integration.Behav. Brain Res.94 , 127–152 (1998).
  • Volkow ND , WangG, FowlerJS et al.: Therapeutic doses of oral methylphenidate significantly increase extracellular dopamine in the human brain.J. Neurosci.21(2) , RC121 (2001).
  • Swanson J , GuptaS, GuintaD et al.: Acute tolerance to methylphenidate in the treatment of attention deficit hyperactivity disorder in children.Clin. Pharmacol. Ther.66 , 295–305 (1999).
  • Bogle KE , SmithBH: Illicit methylphenidate use: a review of prevalence, availability, pharmacology, and consequences.Curr. Drug Abuse Rev.2 , 157–176 (2009).
  • Rabiner DL , AnastopoulosAD, CostelloEJ, HoyleRH, SwartzwelderHS: Predictors of nonmedical ADHD medication use by college students.J. Atten. Disord.13 , 640–648 (2010).
  • Tuttle JP , ScheurichNE, RanseenJ: Prevalence of ADHD diagnosis and nonmedical prescription stimulant use in medical students.Acad. Psychiatry34 , 220–223 (2010).
  • Faraj BA , IsrailiZH, PerelJM et al.: Metabolism and disposition of methylphenidate-14C: studies in man and animals.J. Pharmacol. Exp. Ther.191 , 535–547 (1974).
  • Patrick KS , KiltsCD, BreeseGR: Synthesis and pharmacology of hydroxylated metabolites of methylphenidate.J. Med. Chem.24 , 1237–1240 (1981).
  • Redalieu E , BartlettMF, WaldesLM et al.: A study of methylphenidate in man with respect to its major metabolite.Drug Metab. Dispos.10 , 708–709 (1982).
  • Aoyama T , KotakiH, HondaY, NakagawaF: Kinetic analysis of enantiomers of threo-methylphenidate and its metabolite in two healthy subjects after oral administration as determined by a gas chromatographic-mass spectrometric method.J. Pharm. Sci.79 , 465–469 (1990).
  • Sun Z , MurryDJ, SanghaniSP et al.: Methylphenidate is stereoselectively hydrolyzed by human carboxylesterase CES1A1.J. Pharmacol. Exp. Ther.310 , 469–476 (2004).
  • LeVasseur NL , ZhuHJ, MarkowitzJS, DeVaneCL, PatrickKS: Enantiospecific gas chromatographic-mass spectrometric analysis of urinary methylphenidate: implications for phenotyping.J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.862 , 140–149 (2008).
  • Zhu HJ , AppelDI, PetersonYK, WangZ, MarkowitzJS: Identification of selected therapeutic agents as inhibitors of carboxylesterase 1: potential sources of metabolic drug interactions.Toxicology270 , 59–65 (2010).
  • Koehm M , KauertGF, ToennesSW: Influence of ethanol on the pharmacokinetics of methylphenidate‘s metabolites ritalinic acid and ethylphenidate.Arzneimittelforschung60 , 238–244 (2010).
  • Patrick KS , StraughnAB, MinhinnettRR et al.: Influence of ethanol and gender on methylphenidate pharmacokinetics and pharmacodynamics.Clin. Pharmacol. Ther.81 , 346–353 (2007).
  • Zhu HJ , PatrickKS, YuanHJ et al.: Two CES1 gene mutations lead to dysfunctional carboxylesterase 1 activity in man: clinical significance and molecular basis.Am. J. Hum. Genet.82 , 1241–1248 (2008).
  • Repantis D , SchlattmannP, LaisneyO, HeuserI: Modafinil and methylphenidate for neuroenhancement in healthy individuals: a systematic review.Pharmacol. Res.62 , 187–206 (2010).
  • Maher B : Poll results: look who‘s doping.Nature452 , 674–675 (2008).
  • Tao G , LongshanZ, KehuaW et al.: Population pharmacokinetics of modafinil in Chinese Han, Mongolian, Korean, Uygur, and Hui healthy subjects determined by nonlinear mixed-effects modeling.Ther. Drug Monit.32 , 189–193 (2010).
  • Wong YN , KingSP, SimcoeD et al.: Open-label, single-dose pharmacokinetic study of modafinil tablets: influence of age and gender in normal subjects.J. Clin. Pharmacol.39 , 281–288 (1999).
  • Burnat P , RoblesF, DoB: High-performance liquid chromatographic determination of modafinil and its two metabolites in human plasma using solid-phase extraction.J. Chromatogr. B706 , 295–304 (1998).
  • Tseng YL , UraletsV, LinCT, KuoFH: Detection of modafinil in human urine by gas chromatography-mass spectrometry.J. Pharm. Biomed. Anal.39 , 1042–1045 (2005).
  • Donovan JL , MalcolmRJ, MarkowitzJS, DeVaneCL: Chiral analysis of D- and L-modafinil in human serum: application to human pharmacokinetic studies.Ther. Drug Monit.25 , 197–202 (2003).
  • Robertson P , DeCoryHH, MadanA, ParkinsonA: In vitro inhibition and induction of human hepatic cytochrome P450 enzymes by modafinil.Drug Metab. Dispos.28 , 664–671 (2000).
  • Darwish M , KirbyM, RobertsonP Jr, Hellriegel ET: Interaction profile of armodafinil with medications metabolized by cytochrome P450 enzymes 1A2, 3A4 and 2C19 in healthy subjects. Clin. Pharmacokinet.47 , 61–74 (2008).
  • Zhu HJ , WangJS, DonovanJL et al.: Interactions of attention-deficit/hyperactivity disorder therapeutic agents with the efflux transporter P-glycoprotein.Eur. J. Pharmacol.578 , 148–158 (2008).
  • Passie T , HalpernJH, StichtenothDO, EmrichHM, HintzenA: The pharmacology of lysergic acid diethylamide: a review.CNS Neurosci. Ther.14 , 295–314 (2008).
  • Poch GK , KletteKL, HallareDA et al.: Detection of metabolites of lysergic acid diethylamide (LSD) in human urine specimens: 2-oxo-3-hydroxy-LSD, a prevalent metabolite of LSD.J. Chromatogr. B Biomed. Sci. Appl.724 , 23–33 (1999).
  • Reuschel SA , EadesD, FoltzRL: Recent advances in chromatographic and mass spectrometric methods for determination of LSD and its metabolites in physiological specimens.J. Chromatogr. B Biomed. Sci. Appl.733 , 145–159 (1999).
  • Nelson CC , FoltzRL: Chromatographic and mass spectrometric methods for determination of lysergic acid diethylamide (LSD) and metabolites in body fluids.J. Chromatogr.580 , 97–109 (1992).
  • Klette KL , AndersonCJ, PochGK, NimrodAC, ElSohlyMA: Metabolism of lysergic acid diethylamide (LSD) to 2-oxo-3-hydroxy LSD (O-H-LSD) in human liver microsomes and cryopreserved human hepatocytes.J. Anal. Toxicol.24 , 550–556 (2000).
  • Verstraete AG , Van de Velde EJ: 2-oxo-3-hydroxy-LSD: an important LSD metabolite? Acta Clin. Belg. Suppl.1 , 94–96 (1999).
  • Yu AM : Indolealkylamines: biotransformations and potential drug–drug interactions.AAPS J.10 , 242–253 (2008).
  • Valdes LJ III: Salvia divinorum and the unique diterpene hallucinogen, Salvinorin (divinorin) A. J. Psychoactive Drugs26 , 277–283 (1994).
  • Roth BL , BanerK, WestkaemperR et al.: Salvinorin A: a potent naturally occurring nonnitrogenous κ opioid selective agonist.Proc. Natl Acad. Sci. USA99 , 11934–11939 (2002).
  • Gonzalez D , RibaJ, BousoJC, Gomez-JaraboG, BarbanojMJ: Pattern of use and subjective effects of Salvia divinorum among recreational users.Drug Alcohol Depend.85 , 157–162 (2006).
  • Schmidt MS , PrisinzanoTE, TidgewellK et al.: Determination of Salvinorin A in body fluids by high performance liquid chromatography-atmospheric pressure chemical ionization.J. Chromatogr. B Analyt. Technol. Biomed. Life Sci.818 , 221–225 (2005).
  • Valdes LJ III, Chang HM, Visger DC, Koreeda M: Salvinorin C, a new neoclerodane diterpene from a bioactive fraction of the hallucinogenic Mexican mint Salvia divinorum. Org. Lett.3 , 3935–3937 (2001).
  • Schmidt MD , SchmidtMS, ButelmanER et al.: Pharmacokinetics of the plant-derived k-opioid hallucinogen salvinorin A in nonhuman primates.Synapse58 , 208–210 (2005).
  • Teksin ZS , LeeIJ, NemiebokaNN et al.: Evaluation of the transport, in vitro metabolism and pharmacokinetics of Salvinorin A, a potent hallucinogen.Eur. J. Pharm. Biopharm.72(2) , 471–477 (2009).
  • Hasler F , BourquinD, BrenneisenR, BarT, VollenweiderFX: Determination of psilocin and 4-hydroxyindole-3-acetic acid in plasma by HPLC-ECD and pharmacokinetic profiles of oral and intravenous psilocybin in man.Pharm. Acta Helv.72 , 175–184 (1997).
  • Passie T , SeifertJ, SchneiderU, EmrichHM: The pharmacology of psilocybin.Addict. Biol.7 , 357–364 (2002).
  • Gonzalez-Maeso J , WeisstaubNV, ZhouM et al.: Hallucinogens recruit specific cortical 5-HT(2A) receptor-mediated signaling pathways to affect behavior.Neuron53 , 439–452 (2007).
  • Grieshaber AF , MooreKA, LevineB: The detection of psilocin in human urine.J. Forensic Sci.46 , 627–630 (2001).
  • Sticht G , KafersteinH: Detection of psilocin in body fluids.Forensic Sci. Int.113 , 403–407 (2000).
  • Kamata T , NishikawaM, KatagiM, TsuchihashiH: Direct detection of serum psilocin glucuronide by LC/MS and LC/MS/MS: time-courses of total and free (unconjugated) psilocin concentrations in serum specimens of a ‘magic mushroom‘ user.Forensic Toxicol.24 , 36–40 (2006).
  • Manevski N , KurkelaM, HöglundC et al.: Glucuronidation of psilocin and 4-hydroxyindole by the human UDP-glucuronosyltransferases.Drug Metab. Dispos.38(3) , 386–395 (2010).
  • Benowitz NL : Nicotine addiction.N. Engl. J. Med.362 , 2295–2303 (2010).
  • Hukkanen J , JacobP III, Benowitz NL: Metabolism and disposition kinetics of nicotine. Pharmacol. Rev.57 , 79–115 (2005).
  • Benowitz NL , HukkanenJ, JacobP III: Nicotine chemistry, metabolism, kinetics and biomarkers. Handb. Exp. Pharmacol.192 , 29–60 (2009).
  • Malaiyandi V , SellersEM, TyndaleRF: Implications of CYP2A6 genetic variation for smoking behaviors and nicotine dependence.Clin. Pharmacol. Ther.77 , 145–158 (2005).
  • Lerman C , TyndaleR, PattersonF et al.: Nicotine metabolite ratio predicts efficacy of transdermal nicotine for smoking cessation.Clin. Pharmacol. Ther.79 , 600–608 (2006).
  • Rubinstein ML , BenowitzNL, AuerbackGM, MoscickiAB: Rate of nicotine metabolism and withdrawal symptoms in adolescent light smokers.Pediatrics122 , e643–e647 (2008).
  • Dempsey D , TutkaP, JacobP III et al.: Nicotine metabolite ratio as an index of cytochrome P450 2A6 metabolic activity. Clin. Pharmacol. Ther.76 , 64–72 (2004).
  • Swan GE , BenowitzNL, LessovCN et al.: Nicotine metabolism: the impact of CYP2A6 on estimates of additive genetic influence.Pharmacogenet. Genomics15 , 115–125 (2005).
  • Nakajima M , KuroiwaY, YokoiT: Interindividual differences in nicotine metabolism and genetic polymorphisms of human CYP2A6.Drug Metab. Rev.34 , 865–877 (2002).
  • Benowitz NL , Perez-StableEJ, FongI et al.: Ethnic differences in N-glucuronidation of nicotine and cotinine.J. Pharmacol. Exp. Ther.291 , 1196–1203 (1999).
  • Perez-Stable EJ , HerreraB, JacobP III, Benowitz NL: Nicotine metabolism and intake in black and white smokers. JAMA280 , 152–156 (1998).
  • Benowitz NL , Perez-StableEJ, HerreraB, JacobP III: Slower metabolism and reduced intake of nicotine from cigarette smoking in Chinese–Americans. J. Natl Cancer Inst.94 , 108–115 (2002).
  • Kandel DB , HuMC, SchaffranC, UdryJR, BenowitzNL: Urine nicotine metabolites and smoking behavior in a multiracial/multiethnic national sample of young adults.Am. J. Epidemiol.165 , 901–910 (2007).
  • Higashi E , FukamiT, ItohM et al.: Human CYP2A6 is induced by estrogen via estrogen receptor.Drug Metab. Dispos.35 , 1935–1941 (2007).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.