Strategies to assess the drug interaction potential in translational medicine

• DEPARTMENT OF HEALTH AND HUMAN SERVICES, US FOOD AND DRUG ADMINISTRATION, CDER, CBER: Guidance for industry. Drug metabolism/drug interaction studies in the drug development process: studies in vitro. (1997).
   Google Scholar
• US DEPARTMENT OF HEALTH AND HUMAN SERVICES, FOOD AND DRUG ADMINISTRATION, CDER, CBER: Guidance for Industry. In vivo drug metabolism/drug interaction studies. Study design, data analysis, and recommendations for dosing and labelling. (1999).
   Google Scholar
• EMEA: Note for guidance on the investigation of drug interactions. CPMP/EWP/560/95 (1997).
   Google Scholar
• LAZAROU J, POMERANZ BH, COREY PN: Incidence of adverse drug reactions in hospitalized patients. A meta-analysis of prospective studies. JAMA (1998) 279(15):1200-1205.
   PubMed Web of Science ®Google Scholar
• KUHLMANN J, MÜCK W: Clinical–pharmacological strategies to assess drug interaction potential during drug development. Drug Safety (2001) 24(10):715-725.
   PubMed Web of Science ®Google Scholar
• OBACH S, WALSKY R, VENKATAKRISHNAN K, HOUSTO B, TREMAINE L: In vitro cytochrome P450 inhibition data and the prediction of drug–drug interactions: qualitative relationship, quantitative predictions, and the rank-order approach. Clin. Pharmacol. Ther. (2005) 78:582-592.
   PubMed Web of Science ®Google Scholar
• LIN JH, LU AY: Role of pharmacokinetics and metabolism in drug discovery and development. Pharmacol. Rev. (1997) 49(4):403-449.
   PubMed Web of Science ®Google Scholar
• PELKONEN O, TURPEINEN M, VUSITALO J et al.: Prediction of drug metabolism and interactions on the basis of in vitro investigations. Basic Clin. Pharmacol. Toxicol. (2005) 96(3):167-175.
   PubMed Web of Science ®Google Scholar
• SINGH SS: Preclinical pharmacokinetics: an approach towards safer and efficacious drugs. Curr. Drug Metab. (2006) 7(2):165-182.
   PubMed Web of Science ®Google Scholar
• PERSIANI S: Translational medicine. IDrugs (2006) 9(4):253-255.
   PubMed Web of Science ®Google Scholar
• TUK B, VAN OOSTENBRUGGEN MF, HERBEN VM et al.: Characterization of the pharmacodynamic interaction between parent drug and active metabolite in vivo: midazolam and α-OH-midazolam. J. Pharmacol. Exp. Ther. (1999) 289(2):1067-1074.
   PubMed Web of Science ®Google Scholar
• AMIDON GL, LENNENNA SH, SHAM VP et al.: A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm. Res. (1995) 12(3):413-420.
   PubMed Web of Science ®Google Scholar
• VAN BREEMEN RB, LI Y: Caco-2 cell permeability assays to measure drug absorption. Expert Opin. Drug Metab. Toxicol. (2005) 1(2):175-185.
   PubMedGoogle Scholar
• JOHNSON SR, ZHENG W: Recent progress in the computational prediction of aqueous solubility and absorption. AAPS J. (2006) 8(1):E27-E40.
   PubMed Web of Science ®Google Scholar
• MARTINEZ MN, AMIDON GL: A mechanism approach to understanding the factors affecting drug absorption: a review of fundamentals. J. Clin. Pharmacol. (2002) 42:620-643.
   PubMed Web of Science ®Google Scholar
• WALLACE SM, VERBEECK RK: Plasma protein binding of drugs in the elderly. Clin. Pharmacokinet. (1987) 12:41-72.
   PubMed Web of Science ®Google Scholar
• PACIFICI GM, VIANI A: Methods of determining plasma and tissue binding of drugs. Clin. Pharmacokinet. (1992) 23(6):449-468.
   PubMed Web of Science ®Google Scholar
• GRIME K, RILEY RJ: The impact of in vitro binding on in vitro–in vivo extrapolations, projections of metabolic clearance and clinical drug–drug interactions. Curr. Drug Metab. (2006) 7:251-264.
   PubMed Web of Science ®Google Scholar
• BERTUCCI C, DOMENICI E: Reversible and covalent binding of drugs to human serum albumin: methodological approaches and physiological relevance. Curr. Med. Chem. (2002) 9(15):1463-1481.
   PubMed Web of Science ®Google Scholar
• WAN H, REHNGREN M: High-throughput screening of protein binding by equilibrium dialysis combined with liquid chromatography and mass spectrometry. J. Chromatogr. A (2006) 1102(1-2):125-134.
   PubMed Web of Science ®Google Scholar
• BANKER MJ, CLARK TH, WILLIAMS JA: Development and validation of a 96-well equilibrium dialysis apparatus for measuring plasma protein binding. J. Pharm. Sci. (2003) 92(5):967-974.
   PubMed Web of Science ®Google Scholar
• FUNG EN, CHEN YH, LAU YY: Semi-automatic high-throughput determination of plasma protein binding using a 96-well plate filtrate assembly and fast liquid chromatography-tandem mass spectrometry. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. (2003) 795(2):187-194.
   PubMed Web of Science ®Google Scholar
• THUMMEL KE, WILKINSON GR: In vitro and in vivo drug interactions involving human CYP3A. Ann. Rev. Pharmacol. Toxicol. (1998) 38:389-430.
   PubMed Web of Science ®Google Scholar
• TUCKER GT, HOUSTON JB, HUANG S-M: Optimizing drug development: strategies to assess drug metabolism/transporter interaction potential-towards a consensus. Br. J. Clin. Pharmacol. (2001) 52:107-117.
   PubMed Web of Science ®Google Scholar
• RODRIGUES AD: Commentary: use of in vitro human metabolism studies in drug development. An industrial perspective. Biochem. Pharmacol. (1994) 48(12):2147-2156.
   PubMed Web of Science ®Google Scholar
• BJORNSSON TD, CALLAGHAN JT, EINOLF HJ et al.: The conduct of in vitro and in vivo drug–drug interaction studies: a PhRMA perspective. J. Clin. Pharmacol. (2003) 43:443-469.
   PubMed Web of Science ®Google Scholar
• BJORNSSON TD, CALLAGHAN JT, EINOLF HJ et al.: The conduct of in vitro and in vivo drug–drug interaction studies: a pharmaceutical research and manufacturers of America (PhRMA) perspective. Drug Metab. Dispos. (2003) 31:815-832.
   PubMed Web of Science ®Google Scholar
• ITO K, IWATSUBO T, KANAMITSU S et al.: Prediction of pharmacokinetic alterations caused by drug–drug interactions: metabolic interaction in the liver. Pharmacol. Rev. (1998) 50:387-411.
   PubMed Web of Science ®Google Scholar
• PRAKASH C, KAMEL A, CUI D et al.: Identification of the major human liver cytochrome P450 isoform(s) responsible for the formation of the primary metabolites of ziprasidone and prediction of possible drug interactions. Br. J. Clin. Pharmacol. (2000) 49(Suppl. 1):35S-42S.
   PubMed Web of Science ®Google Scholar
• BOGAARDS JJP, BERTRAND M, JACKSON P et al.: Determining the best animal model for human cytochrome P450 activities: a comparison of mouse, rat, rabbit, dog, micropig, monkey and man. Xenobiotica (2000) 30(12):1131-1152.
   PubMed Web of Science ®Google Scholar
• GUENGERICH FP: Role of cytochrome P450 enzymes in drug–drug interactions. Adv. Pharmacol. (1997) 43:7-35.
   PubMedGoogle Scholar
• SHARER JE, SHIPLEY LA, VANDENBRANDEN MR et al.: Comparisons of Phase I and Phase II in vitro hepatic enzyme activities of human, dog, rhesus monkey, and cynomolgus monkey. Drug Metab. Dispos. (1995) 23(11):1231-1241.
   PubMed Web of Science ®Google Scholar
• WANG RW, NEWTON DJ, LIU N et al.: Human cytochrome P450 3A4: in vitro drug–drug interaction patterns are substrate-dependent. Drug Metab. Dispos. (2000) 28(3):360-366.
   PubMed Web of Science ®Google Scholar
• GUENGERICH FP: Comparison of catalytic selectivity of cytochrome P450 subfamily enzymes from different species. Chem. Biol. Interact. (1997) 106(3):161-182.
   PubMed Web of Science ®Google Scholar
• HARRIS RZ, BENET LZ, SCHWARTZ JB: Gender effects in pharmacokinetics and pharmacodynamics. Drugs (1995) 50(2):222-239.
   PubMed Web of Science ®Google Scholar
• GLEITER CH, GUNDERT-REMY U: Gender differences in pharmacokinetics. Eur. J. Drug Metab. Pharmacokinet. (1996) 21(2):123-128.
   PubMed Web of Science ®Google Scholar
• BEIERLE I, MEIBOHM B, DERENDORF H: Gender differences in pharmacokinetics and pharmacodynamics. Int. J. Clin. Pharmacol. Ther. (1999) 37(11):529-547.
   PubMed Web of Science ®Google Scholar
• BURSTEIN AH, REISS WG, KANTOR E et al.: Cytochrome P450 3A4 activity in premenopausal and postmenopausal women, based on 6-β-hydroxycortisol: cortisol ratios. Pharmacotherapy (1998) 18(6):1271-1276.
   PubMed Web of Science ®Google Scholar
• KRISHNA DR, SHEKAR MS: Cytochrome P450 3A: genetic polymorphisms and interethnic differences. Methods Find. Exp. Clin. Pharmacol. (2005) 27(8):559-567.
   PubMed Web of Science ®Google Scholar
• PELKONEN O, RAUNIO H: In vitro screening of drug metabolism during drug development: can we trust the predictions? Expert Opin. Drug Metab. Toxicol. (2005) 1(1):49-59.
   PubMedGoogle Scholar
• WRIGHTON SA, RING BJ, VANDEN BRANDEN M: The use of In vitro metabolism techniques in the planning and interpretation of drug safety studies. Toxicol. Pathol. (1995) 23(2):199-208.
   PubMed Web of Science ®Google Scholar
• BLANCHARD N, RICHERT L, COASSOLO P et al.: Qualitative and quantitative assessment of drug–drug interaction potential in man, based in Ki, IC50 and inhibition concentration. Curr. Drug Metab. (2004) 5:147-156.
   PubMed Web of Science ®Google Scholar
• RODRIGUES AD, LIN JH: Screening of drug candidates for their drug–drug interaction potential. Curr. Opin. Chem. Biol. (2001) 5:396-401.
   PubMed Web of Science ®Google Scholar
• ERHARDT PW: A human drug metabolism database: potential roles in the quantitative predictions of drug metabolism and metabolism-related drug–drug interactions. Curr. Drug Metab. (2003) 4(5):411-422.
   PubMed Web of Science ®Google Scholar
• LAUNAY-VACHER V, IZZEDINE H, KARIE S et al.: Renal tubular drug transporters. Nephron. Physiol. (2006) 103(3):97-106.
   PubMed Web of Science ®Google Scholar
• DRESSER MJ, KAUSHAL LEABMAN M, GIACOMINI KM: Transporters involved in the elimination of drugs in the kidney: organic anion transporters and organic cation transporters. J. Pharm. Sci. (2001) 90(4):397-421.
   PubMed Web of Science ®Google Scholar
• SHITARA Y, SATO H, SUGIYAMA Y: Evaluation of drug–drug interaction in the hepatobiliary and renal transport of drugs. Ann. Rev. Pharmacol. Toxicol. (2005) 45:689-723.
   PubMed Web of Science ®Google Scholar
• MIZUNO N, NIWA T, YOTSUMOTO Y et al.: Impact of drug transporter studies on drug discovery and development. Pharmacol. Rev. (2003) 55(8):425-461.
   PubMed Web of Science ®Google Scholar
• KUSUHARA H, SUGIYAMA Y: Drug-drug interactions involving the membrane transport process. In: Drug–drug interactions. Rodrigues AD (Ed.), Marcel Dekker, New York, USA (2002):123-188.
   Google Scholar
• PETZINGER E, GEYER J: Drug transporters in pharmacokinetics. Arch. Pharmacol. (2006) 376(6):465-475.
   Google Scholar
• KEMPER EM, VAN ZANDBERGEN AE, CLEYPOOL C et al.: Increased penetration of paclitaxel into brain by inhibition of P-glycoprotein. Clin. Cancer Res. (2003) 9:2849-2855.
   PubMed Web of Science ®Google Scholar
• SADEQUE AJM, WANDEL C, HE H et al.: Increased drug delivery to the brain by P-glycoprotein inhibition. Clin. Pharmacol. Ther. (2000) 68:231-237.
   PubMed Web of Science ®Google Scholar
• LIN JH: Drug–drug interaction mediated by inhibition and induction of P-glycoprotein. Adv. Drug Deliv. Rev. (2003) 55:53-81.
   PubMed Web of Science ®Google Scholar
• GREINER B, EICHELBAUM M, FRITZ P et al.: The role of intestinal P-glycoprotein in the interaction of digoxin and rifampin. J. Clin. Invest. (1999) 104:147-153.
   PubMed Web of Science ®Google Scholar
• SCHWARZ UI, GRAMATTE T, KRAPPWEIS J et al.: P-glycoprotein inhibitor erythromycin increases oral bioavailability of talinolol in humans. Int. J. Clin. Pharmacol. Ther. (2000) 38:161-167.
   PubMed Web of Science ®Google Scholar
• KOVARIK JM, RIGAUDY L, GUERRET M et al.: Longitudinal assessment of a P-glycoprotein-mediated drug interaction of valspodar on digoxin. Clin. Pharmacol. Ther. (1999) 66(4):391-400.
   PubMed Web of Science ®Google Scholar
• HUISMAN MT, SMIT JW, WILTSHIRE HR et al.: Assessing safety and efficacy of directed P-glycoprotein inhibition to improve the pharmacokinetic properties of saquinavir coadministered with ritonavir. J. Pharmacol. Exp. Ther. (2003) 304(2):596-602.
   PubMed Web of Science ®Google Scholar
• MAHADEVAN D, SHIRAHATTI N: Strategies of targeting the multidrug resistance-1 (MDR1)/P-gp transporter in human malignancies. Curr. Cancer Drug Targets (2005) 5(6):445-455.
   PubMed Web of Science ®Google Scholar
• LESLIE EM, DEELEY RG, COLE SP: Multidrug resistance proteins: role of P-glycoprotein, MRP1, MRP2, and BCRP(ABCG2) in tissue defense. Toxicol. Appl. Pharmacol. (2005) 204(3):216-237.
   PubMed Web of Science ®Google Scholar
• SHITARA Y, ITOH T, SATO H et al.: Inhibition of transporter-mediated hepatic uptake as a mechanism for drug–drug interaction between cerivastatin and cyclosporin A. J. Pharmacol. Exp. Ther. (2003) 304(2):610-616.
   PubMed Web of Science ®Google Scholar
• YAMASHIRO W, MAEDA K, HIROUCHI M et al.: Involvement of transporters in the hepatic uptake and biliary excretion of valsartan, a selective antagonist of the angiotensin II AT 1-receptor, in humans. Drug Metab. Dispos. (2006) 34(7):1247-1254.
   PubMed Web of Science ®Google Scholar
• KAJOSAARI LI, NIEMI M, NEUVONEN M et al.: Cyclosporine markedly raises the plasma concentrations of repaglinide. Clin. Pharmacol. Ther. (2005) 78(4):388-399.
   PubMed Web of Science ®Google Scholar
• TSURUOKA S, IOKA T, WAKAUMI M et al.: Severe arrhythmia as a result of the interaction of cetirizine and pilsicainide in a patient with renal insufficiency: first case presentation showing competition for excretion via renal multidrug resistance protein 1 and organic cation transporter 2. Clin. Pharmacol. Ther. (2006) 79(4):389-396.
   PubMed Web of Science ®Google Scholar
• BALIMANE PV, HAN Y-H, CHONG S: Current industrial practices of assessing permeability and P-glycoprotein interaction. AAPS J. (2006) 8(1):E1-E13.
   PubMed Web of Science ®Google Scholar
• HIRANO M, MAEDA K, SHITARA Y, SUGIYAMA Y: Drug–drug interaction between pitavastatin and various drugs via OATP1B1. Drug Metab. Dispos. (2006) 34(7):1229-1236.
   PubMed Web of Science ®Google Scholar
• GUO A, MARINARO W, HU P et al.: Delineating the contribution of secretory transporters in efflux of etoposide using madin-darby canine kidney (MDCK) cells overexpressing P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP1), and canalicular multispecific organic anion transporter (cMOAT). Drug Metab. Dispos. (2002) 30(4):457-463.
   PubMed Web of Science ®Google Scholar
• TOLLE-SANDER S, GRILL A, JOSHI H et al.: Characterisation of dexloxiglumide in vitro biopharmaceutical properties and active transport. J. Pharm. Sci. (2003) 92(10):1968-1980.
   PubMed Web of Science ®Google Scholar
• SASAKI M, SUZUKI H, AOKI J et al.: Prediction of in vivo biliary clearance from the in vitro transcellular transport of organic anions across a double-transfected madin-darby canine kidney II monolayer expressing both rat organic anion transporting polypeptide 4 and multidrug resistance associated protein 2. Mol. Pharmacol. (2004) 66:450-459.
   PubMed Web of Science ®Google Scholar
• NINOMIYA M, ITO K, HORIE T: Functional analysis of dog multidrug resistance-associated protein 2 (MRP2) in comparison with rat MRP2. Drug Metab. Dispos. (2005) 33(2):225-232.
   PubMed Web of Science ®Google Scholar
• MAGNARIN M, MORELLI M, ROSATI A et al.: Induction of proteins involved in multidrug resistance (P-glycoprotein, MRP1, MRP2, LRP) and of CYP 3A4 by rifampicin in LLC-PK1 cells. Eur. J. Pharmacol. (2004) 483(1):19-28.
   PubMed Web of Science ®Google Scholar
• POLLI J, WRING SA, HUMPHREYS JE et al.: Rational use of in vitro P-glycoprotein assays in drug discovery. J. Pharmacol. Exp. Ther. (2001) 299(2):620-628.
   PubMed Web of Science ®Google Scholar
• RAUTIO J, HUMPHREYS JE, WEBSTER LO et al.: In vitro P-glycoprotein inhibition assays for assessment of clinical drug interaction potential of new drug candidates: a recommendation for probe substrates. Drug Metab. Dispos. (2006) 34(5):786-792.
   PubMed Web of Science ®Google Scholar
• NABA H, KUWAYAMA C, KAKINUMA C et al.: Eisai hyperbilirunemic rat (EHBR) as an animal model affording high drug-exposure in toxicity studies on organic anions. Drug Metab. Pharmacokinet. (2004) 19(5):339-351.
   PubMedGoogle Scholar
• GIESSMANN T, MAY K, MODESS C et al.: Carbamazepine regulates intestinal P-glycoprotein and multidrug resistance protein MRP2 and influences disposition of talinolol in humans. Clin. Pharmacol. Ther. (2004) 76(3):192-200.
   PubMed Web of Science ®Google Scholar
• BOOTH-GENTHE CL, LOUIE SW, CARLINI et al.: Development and characterisation of LLC-PK1 cells containing Sprague–Dawley rat Abcb 1a (Mdr 1a): comparison of rat P-glycoprotein transport to human and mouse. J. Pharmacol. Toxicol. Methods (2006) 54(1):78-89.
   PubMedGoogle Scholar
• SHILLING AD, AZAM F, KAO J et al.: Use of canalicular membrane vesicles (CMVs) from rats, dogs, monkeys and humans to assess drug transport across the canalicular membrane. J. Pharmacol. Toxicol. Methods (2005) 53(3):186-197.
   PubMedGoogle Scholar
• SOHN JW, LEE SY, LEE SJ et al.: MDR1 polymorphisms predict the response to etoposide–cisplatin combination chemotherapy in small cell lung cancer. Jpn. J. Clin. Oncol. (2006) 36(3):137-141.
   PubMed Web of Science ®Google Scholar
• CASCORBI I, GERLOFF T, JOHNE A et al.: Frequency of single nucleotide polymorphisms in the P-glycoprotein drug transporter MDR1 gene in white subjects. Clin. Pharmacol. Ther. (2001): 69(3):169-174.
   PubMed Web of Science ®Google Scholar
• MAYATEPEK E, NEZU J, TAMAI I et al.: Two novel missense mutations of the OCTN2 gene (W283R and V446F) in a patient with primary systemic carnitine deficiency. Hum. Mutat. (2000) 15(1):118.
   PubMedGoogle Scholar
• LEABMAN MK, HUANG CC, KAWAMOTO M et al.: Polymorphisms in a human kidney xenobiotic transporter, OCT2, exhibit altered function. Pharmacogenetics (2002) 12(5):395-405.
   PubMedGoogle Scholar
• TIRONA RG, KIM RB: Pharmacogenomics of organic anion-transporting polypeptides (OATP). Adv. Drug Deliv. Rev. (2002) 54(10):1343-1352.
   PubMed Web of Science ®Google Scholar
• IIDA A, SAITO S, SEKINE A et al.: Catalog of 258 single-nucleotide polymorphisms (SNPs) in genes encoding three organic anion transporters, three organic anion-transporting polypeptides, and three NADH ubiquinone oxidoreductase flavoproteins. J. Hum. Genet. (2001) 46(11):668-683.
   PubMed Web of Science ®Google Scholar
• HOFFMEYER S, BURK O, VON RICHTER O et al.: Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc. Natl. Acad. Sci. USA (2000) 97(7):3473-3478.
   PubMed Web of Science ®Google Scholar
• SAKAEDA T: MDR1 Genotype-related pharmacokinetics: fact or fiction? Drug Metab. Pharmacokinet. (2005) 20(6):391-414.
   PubMedGoogle Scholar
• EICHELBAUM M, FROMM MF, SCHWAB M: Clinical aspects of the MDR1 (ABCB1) gene polymorphism. Ther. Drug Monit. (2004) 26(2):180-185.
   PubMed Web of Science ®Google Scholar
• LAMBA J, STROM S, VENKATARAMANAN R et al.: MDR1 genotype is associated with hepatic cytochrome P450 3A4 basal and induction phenotype. Clin. Pharmacol. Ther. (2006) 79(4):325-338.
   PubMed Web of Science ®Google Scholar
• WOODAHL EL, HO RJ: The role of MDR1 genetic polymorphisms in interindividual variability in P-glycoprotein expression and function. Curr. Drug Metab. (2004) 5(1):11-19.
   PubMed Web of Science ®Google Scholar
• YUAN R, PARMELEE T, BALIAN JD et al.: Pharmacokinetics and drug disposition. In vitro metabolic interaction studies: experience of the food and drug administration. Clin. Pharmacol. Ther. (1999) 66:9-15.
   PubMed Web of Science ®Google Scholar
• MARROUM PJ, UPPOOR RS, PARMELEE T et al.: In vivo drug–drug interaction studies. A survey of all new molecular entities approved from 1987 to 1997. Clin. Pharmacol. Ther. (2000) 68:280-285.
   PubMed Web of Science ®Google Scholar
• HUANG SM, LESKO LJ, WILLIAMS RL: Assessment of the quality and quantity of drug–drug interaction studies in recent NDA submissions: study design and data analysis issues. J. Clin. Pharmacol. (1999) 39:1006-1014.
   PubMed Web of Science ®Google Scholar
• BHATTARAM VA, BOOTH BP, RAMCHANDANI RP et al.: Impact of pharmacometrics on drug approval and labelling decisions: a survey of 42 new drug applications. AAPS J. (2005) 7(3):E503-E512.
   PubMed Web of Science ®Google Scholar

Websites

• http://www.fda.gov/oc/initiatives/criticalpath/whitepaper.htmlFDA US Dept of Health and Human Services. Challenge and opportunity on the critical path to new medical products. FDA (2004).
   Google Scholar
• http://www.fda.gov/ohrms/dockets/ac/04/briefing/2004-4079B1_04_Topic2-TabA.pdfFDA Center for Drug Evaluation and Research – CDER (2004): Drug interaction studies – study design, data analysis, and implications for dosing and labelling – preliminary concept paper. FDA/CDER (2004).
   Google Scholar
• http://www.solvo.hu/Literature/Scientific%20Literature/Scientific%20Background.html#4cThe role of ABC transporters in drug resistance, metabolism and toxicity. Solvo Biotechnology (2006).
   Google Scholar
• http://www.bdbiosciences.com/discovery_labware/gentest/products/transporters/transportocytes.shtmlBD Gentest (2006).
   Google Scholar