950
Views
0
CrossRef citations to date
0
Altmetric
Review

Cytochrome P450 2C8 Pharmacogenetics: A Review of Clinical Studies

&
Pages 1489-1510 | Published online: 17 Sep 2009

Bibliography

  • Totah RA , RettieAE: Cytochrome P450 2C8: substrates, inhibitors, pharmacogenetics, and clinical relevance.Clin. Pharmacol. Ther.77 , 341–352 (2005).
  • Evans WE , RellingMV: Moving towards individualized medicine with pharmacogenomics.Nature429 , 464–468 (2004).
  • Klose TS , BlaisdellJA, GoldsteinJA: Gene structure of CYP2C8 and extrahepatic distribution of the human CYP2Cs.J. Biochem. Mol. Toxicol.13 , 289–295 (1999).
  • Delozier TC , KisslingGE, CoulterSJ et al.: Detection of human CYP2C8, CYP2C9, and CYP2J2 in cardiovascular tissues.Drug Metab. Dispos.35 , 682–688 (2007).
  • Schoch GA , YanoJK, WesterMR, GriffinKJ, StoutCD, JohnsonEF: Structure of human microsomal cytochrome P450 2C8. Evidence for a peripheral fatty acid binding site.J. Biol. Chem.279 , 9497–9503 (2004).
  • Schoch GA , YanoJK, SansenS, DansettePM, StoutCD, JohnsonEF: Determinants of cytochrome P450 2C8 substrate binding: structures of complexes with montelukast, troglitazone, felodipine, and 9-cis-retinoic acid.J. Biol. Chem.283 , 17227–17237 (2008).
  • Theken KN , LeeCR: Genetic variation in the cytochrome P450 epoxygenase pathway and cardiovascular disease risk.Pharmacogenomics8 , 1369–1383 (2007).
  • Yasar U , LundgrenS, EliassonE et al.: Linkage between the CYP2C8 and CYP2C9 genetic polymorphisms.Biochem. Biophys. Res. Commun.299 , 25–28 (2002).
  • Johnson EF , StoutCD: Structural diversity of human xenobiotic-metabolizing cytochrome P450 monooxygenases.Biochem. Biophys. Res. Commun.338 , 331–336 (2005).
  • Ferguson SS , ChenY, LeCluyseEL, NegishiM, GoldsteinJA: Human CYP2C8 is transcriptionally regulated by the nuclear receptors constitutive androstane receptor, pregnane X receptor, glucocorticoid receptor, and hepatic nuclear factor 4α.Mol. Pharmacol.68 , 747–757 (2005).
  • Kojima K , NagataK, MatsubaraT, YamazoeY: Broad but distinct role of pregnane X receptor on the expression of individual cytochrome p450s in human hepatocytes.Drug Metab. Pharmacokinet.22 , 276–286 (2007).
  • Bahadur N , LeathartJB, MutchE et al.: CYP2C8 polymorphisms in Caucasians and their relationship with paclitaxel 6α-hydroxylase activity in human liver microsomes.Biochem. Pharmacol.64 , 1579–1589 (2002).
  • Rodriguez-Antona C , NiemiM, BackmanJT et al.: Characterization of novel CYP2C8 haplotypes and their contribution to paclitaxel and repaglinide metabolism.Pharmacogenomics J.8 , 268–277 (2008).
  • Saito Y , KatoriN, SoyamaA et al.: CYP2C8 haplotype structures and their influence on pharmacokinetics of paclitaxel in a Japanese population.Pharmacogenet. Genomics17 , 461–471 (2007).
  • Speed WC , KangSP, TuckDP, HarrisLN, KiddKK: Global variation in CYP2C8–CYP2C9 functional haplotypes.Pharmacogenomics J.9(4) , 283–290 (2009).
  • Dai D , ZeldinDC, BlaisdellJA et al.: Polymorphisms in human CYP2C8 decrease metabolism of the anticancer drug paclitaxel and arachidonic acid.Pharmacogenetics11 , 597–607 (2001).
  • Soyama A , SaitoY, HaniokaN et al.: Non-synonymous single nucleotide alterations found in the CYP2C8 gene result in reduced in vitro paclitaxel metabolism.Biol. Pharm. Bull.24 , 1427–1430 (2001).
  • Hichiya H , Tanaka-KagawaT, SoyamaA et al.: Functional characterization of five novel CYP2C8 variants, G171S, R186X, R186G, K247R, and K383N, found in a Japanese population.Drug Metab. Dispos.33 , 630–636 (2005).
  • Yki-Jarvinen H : Thiazolidinediones.N. Engl. J. Med.351 , 1106–1118 (2004).
  • American Diabetes Association. Standards of medical care in diabetes – 2008. Diabetes Care31 , S12–S54 (2008).
  • Baldwin SJ , ClarkeSE, CheneryRJ: Characterization of the cytochrome P450 enzymes involved in the in vitro metabolism of rosiglitazone.Br. J. Clin. Pharmacol.48 , 424–432 (1999).
  • Jaakkola T , LaitilaJ, NeuvonenPJ, BackmanJT: Pioglitazone is metabolised by CYP2C8 and CYP3A4 in vitro: potential for interactions with CYP2C8 inhibitors.Basic Clin. Pharmacol. Toxicol.99 , 44–51 (2006).
  • Yamazaki H , ShibataA, SuzukiM et al.: Oxidation of troglitazone to a quinone-type metabolite catalyzed by cytochrome P-450 2C8 and P-450 3A4 in human liver microsomes.Drug Metab. Dispos.27 , 1260–1266 (1999).
  • Avandia Prescribing Information. GlaxoSmithKline (2007).
  • Actos Prescribing Information. Takeda Pharmaceuticals America, Inc. (2007).
  • Kirchheiner J , ThomasS, BauerS et al.: Pharmacokinetics and pharmacodynamics of rosiglitazone in relation to CYP2C8 genotype.Clin. Pharmacol. Ther.80 , 657–667 (2006).
  • Aquilante CL , BushmanLR, KnutsenSD, BurtLE, RomeLC, KosmiskiLA: Influence of SLCO1B1 haplotype on rosiglitazone pharmacokinetics in healthy volunteers.Hum. Genomics3(1) , 7–16 (2008).
  • Tornio A , NiemiM, NeuvonenPJ, BackmanJT: Trimethoprim and the CYP2C8*3 allele have opposite effects on the pharmacokinetics of pioglitazone.Drug Metab. Dispos.36 , 73–80 (2008).
  • Hruska MW , AmicoJA, LangaeeTY, FerrellRE, FitzgeraldSM, FryeRF: The effect of trimethoprim on CYP2C8 mediated rosiglitazone metabolism in human liver microsomes and healthy subjects.Br. J. Clin. Pharmacol.59 , 70–79 (2005).
  • Pedersen RS , DamkierP, BrosenK: The effects of human CYP2C8 genotype and fluvoxamine on the pharmacokinetics of rosiglitazone in healthy subjects.Br. J. Clin. Pharmacol.62 , 682–689 (2006).
  • Aquilante CL : Pharmacogenetics of thiazolidinedione therapy.Pharmacogenomics8 , 917–931 (2007).
  • Prandin Prescribing Information. Novo Nordisk, Inc. (2006).
  • Bidstrup TB , BjornsdottirI, SidelmannUG, ThomsenMS, HansenKT: CYP2C8 and CYP3A4 are the principal enzymes involved in the human in vitro biotransformation of the insulin secretagogue repaglinide.Br. J. Clin. Pharmacol.56 , 305–314 (2003).
  • Kajosaari LI , LaitilaJ, NeuvonenPJ, BackmanJT: Metabolism of repaglinide by CYP2C8 and CYP3A4 in vitro: effect of fibrates and rifampicin.Basic Clin. Pharmacol. Toxicol.97 , 249–256 (2005).
  • Niemi M , BackmanJT, NeuvonenM, NeuvonenPJ: Effects of gemfibrozil, itraconazole, and their combination on the pharmacokinetics and pharmacodynamics of repaglinide: potentially hazardous interaction between gemfibrozil and repaglinide.Diabetologia46 , 347–351 (2003).
  • Niemi M , NeuvonenPJ, KivistoKT: The cytochrome P4503A4 inhibitor clarithromycin increases the plasma concentrations and effects of repaglinide.Clin. Pharmacol. Ther.70 , 58–65 (2001).
  • Niemi M , LeathartJB, NeuvonenM, BackmanJT, DalyAK, NeuvonenPJ: Polymorphism in CYP2C8 is associated with reduced plasma concentrations of repaglinide.Clin. Pharmacol. Ther.74 , 380–387 (2003).
  • Niemi M , BackmanJT, KajosaariLI et al.: Polymorphic organic anion transporting polypeptide 1B1 is a major determinant of repaglinide pharmacokinetics.Clin. Pharmacol. Ther.77 , 468–478 (2005).
  • Kajosaari LI , NiemiM, NeuvonenM, LaitilaJ, NeuvonenPJ, BackmanJT: Cyclosporine markedly raises the plasma concentrations of repaglinide.Clin. Pharmacol. Ther.78 , 388–399 (2005).
  • Tornio A , NiemiM, NeuvonenM et al.: The effect of gemfibrozil on repaglinide pharmacokinetics persists for at least 12 h after the dose: evidence for mechanism-based inhibition of CYP2C8in vivo.Clin. Pharmacol. Ther.84 , 403–411 (2008).
  • Bidstrup TB , DamkierP, OlsenAK, EkblomM, KarlssonA, BrosenK: The impact of CYP2C8 polymorphism and grapefruit juice on the pharmacokinetics of repaglinide.Br. J. Clin. Pharmacol.61 , 49–57 (2006).
  • Muck W : Clinical pharmacokinetics of cerivastatin.Clin Pharmacokinet.39 , 99–116 (2000).
  • Wang JS , NeuvonenM, WenX, BackmanJT, NeuvonenPJ: Gemfibrozil inhibits CYP2C8-mediated cerivastatin metabolism in human liver microsomes.Drug Metab. Dispos.30 , 1352–1356 (2002).
  • Lucas RA , WeathersbyBB, RoccoVK, PepperJM, ButlerKL: Rhabdomyolysis associated with cerivastatin: six cases within 3 months at one hospital.Pharmacotherapy22 , 771–774 (2002).
  • Law M , RudnickaAR: Statin safety: a systematic review.Am. J. Cardiol.97 , C52–C60 (2006).
  • Omar MA , WilsonJP, CoxTS: Rhabdomyolysis and HMG-CoA reductase inhibitors.Ann. Pharmacother.35 , 1096–1107 (2001).
  • Backman JT , KyrklundC, NeuvonenM, NeuvonenPJ: Gemfibrozil greatly increases plasma concentrations of cerivastatin.Clin. Pharmacol. Ther.72 , 685–691 (2002).
  • Ishikawa C , OzakiH, NakajimaT et al.: A frameshift variant of CYP2C8 was identified in a patient who suffered from rhabdomyolysis after administration of cerivastatin.J. Hum. Genet.49 , 582–585 (2004).
  • Ozaki H , IshikawaCT, IshiiT et al.: Clearance rates of cerivastatin metabolites in a patient with cerivastatin-induced rhabdomyolysis.J. Clin. Pharm. Ther.30 , 189–192 (2005).
  • Scripture CD , PieperJA: Clinical pharmacokinetics of fluvastatin.Clin. Pharmacokinet.40 , 263–281 (2001).
  • Lescol Prescribing Information. Novartis Pharmaceuticals Corporation (2006).
  • Spence JD , MunozCE, HendricksL, LatchinianL, KhouriHE: Pharmacokinetics of the combination of fluvastatin and gemfibrozil.Am. J. Cardiol.76 , A80–A83 (1995).
  • Kirchheiner J , KudliczD, MeiselC et al.: Influence of CYP2C9 polymorphisms on the pharmacokinetics and cholesterol-lowering activity of (-)-3S,5R-fluvastatin and (+)-3R,5S-fluvastatin in healthy volunteers.Clin. Pharmacol. Ther.74 , 186–194 (2003).
  • Shitara Y , SugiyamaY: Pharmacokinetic and pharmacodynamic alterations of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors: drug–drug interactions and interindividual differences in transporter and metabolic enzyme functions.Pharmacol. Ther.112 , 71–105 (2006).
  • Prueksaritanont T , MaB, YuN: The human hepatic metabolism of simvastatin hydroxy acid is mediated primarily by CYP3A, and not CYP2D6.Br. J. Clin. Pharmacol.56 , 120–124 (2003).
  • Crestor Prescribing Information. AstraZeneca Pharmaceticals (2009).
  • Cooper KJ , MartinPD, DaneAL, WarwickMJ, SchneckDW, CantariniMV: The effect of fluconazole on the pharmacokinetics of rosuvastatin.Eur. J. Clin. Pharmacol.58 , 527–531 (2002).
  • Link E , ParishS, ArmitageJ et al.: SLCO1B1 variants and statin-induced myopathy – a genomewide study.N. Engl. J. Med.359 , 789–799 (2008).
  • Chasman DI , PosadaD, SubrahmanyanL, CookNR, StantonVP, Jr, Ridker PM: Pharmacogenetic study of statin therapy and cholesterol reduction. JAMA291 , 2821–2827 (2004).
  • Thompson JF , ManM, JohnsonKJ et al.: An association study of 43 SNPs in 16 candidate genes with atorvastatin response.Pharmacogenomics J.5 , 352–358 (2005).
  • Wilke RA , MooreJH, BurmesterJK: Relative impact of CYP3A genotype and concomitant medication on the severity of atorvastatin-induced muscle damage.Pharmacogenet. Genomics15 , 415–421 (2005).
  • Rodrigues AD : Impact of CYP2C9 genotype on pharmacokinetics: are all cyclooxygenase inhibitors the same?Drug Metab. Dispos.33 , 1567–1575 (2005).
  • Davies NM : Clinical pharmacokinetics of ibuprofen. The first 30 years.Clin. Pharmacokinet.34 , 101–154 (1998).
  • Evans AM : Enantioselective pharmacodynamics and pharmacokinetics of chiral non-steroidal anti-inflammatory drugs.Eur. J. Clin. Pharmacol.42 , 237–256 (1992).
  • Hamman MA , ThompsonGA, HallSD: Regioselective and stereoselective metabolism of ibuprofen by human cytochrome P450 2C.Biochem. Pharmacol.54 , 33–41 (1997).
  • Chang SY , LiW, TraegerSC et al.: Confirmation that cytochrome P450 2C8 (CYP2C8) plays a minor role in (S)-(+)- and (R)-(-)-ibuprofen hydroxylation in vitro.Drug Metab. Dispos.36 , 2513–2522 (2008).
  • Tornio A , NiemiM, NeuvonenPJ, BackmanJT: Stereoselective interaction between the CYP2C8 inhibitor gemfibrozil and racemic ibuprofen.Eur. J. Clin. Pharmacol.63 , 463–469 (2007).
  • Martinez C , Garcia-MartinE, BlancoG, GamitoFJ, LaderoJM, AgundezJA: The effect of the cytochrome P450 CYP2C8 polymorphism on the disposition of (R)-ibuprofen enantiomer in healthy subjects.Br. J. Clin. Pharmacol.59 , 62–69 (2005).
  • Garcia-Martin E , MartinezC, TabaresB, FriasJ, AgundezJA: Interindividual variability in ibuprofen pharmacokinetics is related to interaction of cytochrome P450 2C8 and 2C9 amino acid polymorphisms.Clin. Pharmacol. Ther.76 , 119–127 (2004).
  • Lopez-Rodriguez R , NovalbosJ, Gallego-SandinS et al.: Influence of CYP2C8 and CYP2C9 polymorphisms on pharmacokinetic and pharmacodynamic parameters of racemic and enantiomeric forms of ibuprofen in healthy volunteers.Pharmacol Res.58 , 77–84 (2008).
  • Tang W : The metabolism of diclofenac – enzymology and toxicology perspectives.Curr. Drug Metab.4 , 319–329 (2003).
  • Daly AK , AithalGP, LeathartJB, SwainsburyRA, DangTS, DayCP: Genetic susceptibility to diclofenac-induced hepatotoxicity: contribution of UGT2B7, CYP2C8, and ABCC2 genotypes.Gastroenterology132 , 272–281 (2007).
  • Dorado P , CavacoI, CaceresMC, PiedadeR, RibeiroV, LlerenaA: Relationship between CYP2C8 genotypes and diclofenac 5-hydroxylation in healthy Spanish volunteers.Eur. J. Clin. Pharmacol.64 , 967–970 (2008).
  • Voltaren Prescribing Information. Novartis Pharmaceuticals Corporation (2009).
  • de Abajo FJ , MonteroD, MadurgaM, Garcia Rodriguez LA: Acute and clinically relevant drug-induced liver injury: a population based case–control study. Br. J. Clin. Pharmacol.58 , 71–80 (2004).
  • Aithal GP , DayCP, LeathartJB, DalyAK: Relationship of polymorphism in CYP2C9 to genetic susceptibility to diclofenac-induced hepatitis.Pharmacogenetics10 , 511–518 (2000).
  • Peiro AM , NovalbosJ, ZapaterP et al.: Pharmacogenetic relevance of the CYP2C9*3 allele in a tenoxicam bioequivalence study performed on Spaniards.Pharmacol Res.59 , 62–68 (2009).
  • Martinez C , BlancoG, LaderoJM et al.: Genetic predisposition to acute gastrointestinal bleeding after NSAIDs use.Br. J. Pharmacol.141 , 205–208 (2004).
  • Blanco G , MartinezC, LaderoJM et al.: Interaction of CYP2C8 and CYP2C9 genotypes modifies the risk for nonsteroidal anti-inflammatory drugs-related acute gastrointestinal bleeding.Pharmacogenet. Genomics18 , 37–43 (2008).
  • McGreavey LE , TurnerF, SmithG et al.: No evidence that polymorphisms in CYP2C8, CYP2C9, UGT1A6, PPARδ and PPARγ act as modifiers of the protective effect of regular NSAID use on the risk of colorectal carcinoma.Pharmacogenet. Genomics15 , 713–721 (2005).
  • Rahman A , KorzekwaKR, GroganJ, GonzalezFJ, HarrisJW: Selective biotransformation of taxol to 6 α-hydroxytaxol by human cytochrome P450 2C8.Cancer Res.54 , 5543–5546 (1994).
  • Harris JW , RahmanA, KimBR, GuengerichFP, CollinsJM: Metabolism of taxol by human hepatic microsomes and liver slices: participation of cytochrome P450 3A4 and an unknown P450 enzyme.Cancer Res.54 , 4026–4035 (1994).
  • Somlo G , DoroshowJH, SynoldT et al.: High-dose paclitaxel in combination with doxorubicin, cyclophosphamide and peripheral blood progenitor cell rescue in patients with high-risk primary and responding metastatic breast carcinoma: toxicity profile, relationship to paclitaxel pharmacokinetics and short-term outcome.Br. J. Cancer84 , 1591–1598 (2001).
  • Henningsson A , MarshS, LoosWJ et al.: Association of CYP2C8, CYP3A4, CYP3A5, and ABCB1 polymorphisms with the pharmacokinetics of paclitaxel.Clin. Cancer Res.11 , 8097–8104 (2005).
  • Marsh S , SomloG, LiX et al.: Pharmacogenetic analysis of paclitaxel transport and metabolism genes in breast cancer.Pharmacogenomics J.7 , 362–365 (2007).
  • Marsh S , PaulJ, KingCR, GiffordG, McLeodHL, BrownR: Pharmacogenetic assessment of toxicity and outcome after platinum plus taxane chemotherapy in ovarian cancer: the Scottish Randomised Trial in Ovarian Cancer.J. Clin. Oncol.25 , 4528–4535 (2007).
  • Yamaguchi H , HishinumaT, EndoN et al.: Genetic variation in ABCB1 influences paclitaxel pharmacokinetics in Japanese patients with ovarian cancer.Int. J. Gynecol. Cancer16 , 979–985 (2006).
  • Jiko M , YanoI, SatoE et al.: Pharmacokinetics and pharmacodynamics of paclitaxel with carboplatin or gemcitabine, and effects of CYP3A5 and MDR1 polymorphisms in patients with urogenital cancers.Int. J. Clin. Oncol.12 , 284–290 (2007).
  • Nakajima M , FujikiY, KyoS et al.: Pharmacokinetics of paclitaxel in ovarian cancer patients and genetic polymorphisms of CYP2C8, CYP3A4, and MDR1.J. Clin. Pharmacol.45 , 674–682 (2005).
  • Green H , SoderkvistP, RosenbergP et al.: Pharmacogenetic studies of paclitaxel in the treatment of ovarian cancer.Basic Clin. Pharmacol. Toxicol.104 , 130–137 (2009).
  • Li XQ , BjorkmanA, AnderssonTB, RidderstromM, MasimirembwaCM: Amodiaquine clearance and its metabolism to N-desethylamodiaquine is mediated by CYP2C8: a new high affinity and turnover enzyme-specific probe substrate.J. Pharmacol. Exp. Ther.300 , 399–407 (2002).
  • Jewell H , MaggsJL, HarrisonAC, O‘NeillPM, RuscoeJE, ParkBK: Role of hepatic metabolism in the bioactivation and detoxication of amodiaquine.Xenobiotica25 , 199–217 (1995).
  • Parikh S , OuedraogoJB, GoldsteinJA, RosenthalPJ, KroetzDL: Amodiaquine metabolism is impaired by common polymorphisms in CYP2C8: implications for malaria treatment in Africa.Clin. Pharmacol. Ther.82 , 197–203 (2007).
  • Adjei GO , KristensenK, GokaBQ et al.: Effect of concomitant artesunate administration and cytochrome P4502C8 polymorphisms on the pharmacokinetics of amodiaquine in Ghanaian children with uncomplicated malaria.Antimicrob. Agents Chemother.52 , 4400–4406 (2008).
  • Kim KA , ParkJY, LeeJS, LimS: Cytochrome P450 2C8 and CYP3A4/5 are involved in chloroquine metabolism in human liver microsomes.Arch. Pharm. Res.26 , 631–637 (2003).
  • Rigas JR , FrancisPA, MuindiJR et al.: Constitutive variability in the pharmacokinetics of the natural retinoid, all-trans-retinoic acid, and its modulation by ketoconazole.J. Natl Cancer Inst.85 , 1921–1926 (1993).
  • Kim KA , ChungJ, JungDH, ParkJY: Identification of cytochrome P450 isoforms involved in the metabolism of loperamide in human liver microsomes.Eur. J. Clin. Pharmacol.60 , 575–581 (2004).
  • Niemi M , TornioA, PasanenMK, FredriksonH, NeuvonenPJ, BackmanJT: Itraconazole, gemfibrozil and their combination markedly raise the plasma concentrations of loperamide.Eur. J. Clin. Pharmacol.62 , 463–472 (2006).
  • Wang JS , DeVaneCL: Involvement of CYP3A4, CYP2C8, and CYP2D6 in the metabolism of (R)- and (S)-methadone in vitro.Drug Metab. Dispos.31 , 742–747 (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).
  • Ohyama K , NakajimaM, NakamuraS, ShimadaN, YamazakiH, YokoiT: A significant role of human cytochrome P450 2C8 in amiodarone N-deethylation: an approach to predict the contribution with relative activity factor.Drug Metab. Dispos.28 , 1303–1310 (2000).
  • Soyama A , HaniokaN, SaitoY et al.: Amiodarone N-deethylation by CYP2C8 and its variants, CYP2C8*3 and CYP2C8 P404A.Pharmacol. Toxicol.91 , 174–178 (2002).
  • Becquemont L , MouajjahS, EscaffreO, BeauneP, Funck-BrentanoC, JaillonP: Cytochrome P-450 3A4 and 2C8 are involved in zopiclone metabolism.Drug Metab. Dispos.27 , 1068–1073 (1999).
  • Tornio A , NeuvonenPJ, BackmanJT: The CYP2C8 inhibitor gemfibrozil does not increase the plasma concentrations of zopiclone.Eur. J. Clin. Pharmacol.62 , 645–651 (2006).
  • Attar M , DongD, LingKH, Tang-LiuDD: Cytochrome P450 2C8 and flavin-containing monooxygenases are involved in the metabolism of tazarotenic acid in humans.Drug Metab. Dispos.31 , 476–481 (2003).
  • Tang-Liu DD , MatsumotoRM, UsanskyJI: Clinical pharmacokinetics and drug metabolism of tazarotene: a novel topical treatment for acne and psoriasis.Clin. Pharmacokinet.37 , 273–287 (1999).
  • Covera-HS Prescribing Information. Pfizer (2006).
  • Vogelgesang B , EchizenH, SchmidtE, EichelbaumM: Stereoselective first-pass metabolism of highly cleared drugs: studies of the bioavailability of L- and D-verapamil examined with a stable isotope technique. 1984.Br. J. Clin. Pharmacol.58 , S796–S803; discussion S804–S796 (2004).
  • Tracy TS , KorzekwaKR, GonzalezFJ, WainerIW: Cytochrome P450 isoforms involved in metabolism of the enantiomers of verapamil and norverapamil.Br. J. Clin. Pharmacol.47 , 545–552 (1999).
  • Kerr BM , ThummelKE, WurdenCJ et al.: Human liver carbamazepine metabolism. Role of CYP3A4 and CYP2C8 in 10.11-epoxide formation.Biochem. Pharmacol.47 , 1969–1979 (1994).
  • Chang TK , WeberGF, CrespiCL, WaxmanDJ: Differential activation of cyclophosphamide and ifosphamide by cytochromes P-450 2B and 3A in human liver microsomes.Cancer Res.53 , 5629–5637 (1993).
  • Winter HR , WangY, UnadkatJD: CYP2C8/9 mediate dapsone N-hydroxylation at clinical concentrations of dapsone.Drug Metab. Dispos.28 , 865–868 (2000).
  • Miners JO , CoulterS, BirkettDJ, GoldsteinJA: Torsemide metabolism by CYP2C9 variants and other human CYP2C subfamily enzymes.Pharmacogenetics10 , 267–270 (2000).
  • Sutton D , ButlerAM, NadinL, MurrayM: Role of CYP3A4 in human hepatic diltiazem N-demethylation: inhibition of CYP3A4 activity by oxidized diltiazem metabolites.J. Pharmacol. Exp. Ther.282 , 294–300 (1997).
  • Gil JP , Gil Berglund E: CYP2C8 and antimalaria drug efficacy. Pharmacogenomics8 , 187–198 (2007).

▪ Websites

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.