Strategies to assess the drug interaction potential in translational medicine

Expert Opinion on Drug Metabolism and Toxicology

Volumn 2, Issue 5, 2006, Pages 675-686

  Persiani, Stefano ^a,b   Larger, Patrice ^a,b  

^a Rotta Research Laboratorium   (Italy)

^b Rottapharm Spa ^*  (Italy)

Author keywords

Drug development; Drug discovery; Drug drug interactions; Translational medicine

Indexed keywords

MIBEFRADIL; TERFENADINE;

CARDIOVASCULAR DISEASE; DRUG INDUSTRY; DRUG INTERACTION; DRUG SAFETY; DRUG USE; FOOD AND DRUG ADMINISTRATION; HUMAN; IN VITRO STUDY; IN VIVO STUDY; REVIEW;

ANIMALS; CLINICAL TRIALS; CYTOCHROME P-450 ENZYME SYSTEM; DRUG EVALUATION, PRECLINICAL; DRUG INTERACTIONS; HUMANS; MEMBRANE TRANSPORT PROTEINS; PHARMACEUTICAL PREPARATIONS; PHARMACOKINETICS;

EID: 33846317122     PISSN: 17425255     EISSN: None     Source Type: Journal    
DOI: 10.1517/17425255.2.5.675     Document Type: Review

References (95)

1. 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).
2. 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).
3. EMEA: Note for guidance on the investigation of drug interactions. CPMP/EWP/560/95 (1997).
4. 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.
5. KUHLMANN J, MÜCK W: Clinical-pharmacological strategies to assess drug interaction potential during drug development. Drug Safety (2001) 24(10):715-725.
6. 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.
7. LIN JH, LU AY: Role of pharmacokinetics and metabolism in drug discovery and development. Pharmacol. Rev. (1997) 49(4):403-449. A dated, but still very useful, overview.
8. 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.
9. SINGH SS: Preclinical pharmacokinetics: an approach towards safer and efficacious drugs. Curr. Drug Metab. (2006) 7(2):165-182.
10. PERSIANI S: Translational medicine. IDrugs (2006) 9(4):253-255.
11. 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.
12. 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. An important paper to those involved in this field of research.
13. VAN BREEMEN RB, LI Y: Caco-2 cell permeability assays to measure drug absorption. Expert Opin. Drug Metab. Toxicol. (2005) 1(2):175-185. An extensive review on the topic.
14. JOHNSON SR, ZHENG W: Recent progress in the computational prediction of aqueous solubility and absorption. AAPS J. (2006) 8(1):E27-E40.
15. 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. A fundamental article on the topic of drug absorption.
16. WALLACE SM, VERBEECK RK: Plasma protein binding of drugs in the elderly. Clin. Pharmacokinet. (1987) 12:41-72.
17. PACIFICI GM, VIANI A: Methods of determining plasma and tissue binding of drugs. Clin. Pharmacokinet. (1992) 23(6):449-468. A extensive review on the methods for assessing protein binding.
18. 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.
19. 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.
20. 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.
21. 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.
22. 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.
23. THUMMEL KE, WILKINSON GR: In vitro and in vivo drug interactions involving human CYP3A. Ann. Rev. Pharmacol. Toxicol. (1998) 38:389-430. A dated, but very useful, review on drug interaction involving CYP3A4.
24. 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. A review on DDIs; useful for industrial scientists.
25. RODRIGUES AD: Commentary: use of in vitro human metabolism studies in drug development. An industrial perspective. Biochem. Pharmacol. (1994) 48(12):2147-2156. A review on DDIs in vitro; useful for industrial scientists.
26. 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. A review on DDIs in vitro and in vivo; useful for industrial scientists.
27. 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. A review on DDIs in vitro and in vivo; useful for industrial scientists.
28. 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. A dated, but useful, review on metabolic DDIs.
29. 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.
30. 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. A review to facilitate cross species comparisons and extrapolations to humans.
31. GUENGERICH FP: Role of cytochrome P450 enzymes in drug-drug interactions. Adv. Pharmacol. (1997) 43:7-35. A dated, but useful, review on metabolic DDIs involving CYP450.
32. 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. A review to facilitate cross species comparisons and extrapolations to humans.
33. 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. A review to facilitate the selection of the CYP probe substrates.
34. GUENGERICH FP: Comparison of catalytic selectivity of cytochrome P450 subfamily enzymes from different species. Chem. Biol. Interact. (1997) 106(3):161-182.
35. HARRIS RZ, BENET LZ, SCHWARTZ JB: Gender effects in pharmacokinetics and pharmacodynamics. Drugs (1995) 50(2):222-239. A review on gender related differences in pharmacokinetics and pharmacodynamics.
36. GLEITER CH, GUNDERT-REMY U: Gender differences in pharmacokinetics. Eur. J. Drug Metab. Pharmacokinet. (1996) 21(2):123-128.
37. BEIERLE I, MEIBOHM B, DERENDORF H: Gender differences in pharmacokinetics and pharmacodynamics. Int. J. Clin. Pharmacol. Ther. (1999) 37(11):529-547.
38. 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.
39. KRISHNA DR, SHEKAR MS: Cytochrome P450 3A: genetic polymorphisms and interethnic differences. Methods Find. Exp. Clin. Pharmacol. (2005) 27(8):559-567. A review on genetic polymorphism and interethnic differences in CYP4503A activity.
40. 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.
41. 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. A excellent review for the conduction in vitro studies to predict DDIs.
42. 50 and inhibition concentration. Curr. Drug Metab. (2004) 5:147-156.
43. RODRIGUES AD, LIN JH: Screening of drug candidates for their drug-drug interaction potential. Curr. Opin. Chem. Biol. (2001) 5:396-401.
44. 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.
45. LAUNAY-VACHER V, IZZEDINE H, KARIE S et al.: Renal tubular drug transporters. Nephron. Physiol. (2006) 103(3):97-106. A excellent review on renal drug transporters.
46. 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.
47. 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.
48. 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. Extensive review on drug transporters in drug research and development and their clinical implications.
49. 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. Extensive review on transporter classification, localisation and prediction of DDIs.
50. PETZINGER E, GEYER J: Drug transporters in pharmacokinetics. Arch. Pharmacol. (2006) 376(6):465-475. Review of the role of transporters in pharmacokinetics that introduces the extended phase concept.
51. 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.
52. 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.
53. LIN JH: Drug-drug interaction mediated by inhibition and induction of P-glycoprotein. Adv. Drug Deliv. Rev. (2003) 55:53-81. Comprehensive review of physiological role and involvement of P-glycoprotein in DDIs.
54. 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.
55. 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.
56. 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.
57. 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. Review on effects of P-glycoprotein inhibition on exposure, distribution, and application of knockout mice as a model.
58. 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.
59. 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. Review on the physiology of efflux pumps in different tissues and their role in diet and toxicants interactions.
60. 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. Examples on the experimental and theoretical approaches to elucidate transporter-mediated DDIs.
61. 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. Details in vitro and in vivo studies to investigate drug transporter-mediated elimination.
62. KAJOSAARI LI, NIEMI M, NEUVONEN M et al.: Cyclosporine markedly raises the plasma concentrations of repaglinide. Clin. Pharmacol. Ther. (2005) 78(4):388-399.
63. 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.
64. BALIMANE PV, HAN Y-H, CHONG S: Current industrial practices of assessing permeability and P-glycoprotein interaction. AAPS J. (2006) 8(1):E1-E13.
65. 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. Use of various cell expression systems and hepatocytes to predict DDIs.
66. 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.
67. 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.
68. 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.
69. 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.
70. 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.
71. 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. Detailed description of the conduction and interpretation of the assays used for P-glycoprotein substrate identification.
72. 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. A review for a better selection of P-glycoprotein inhibition assay procedures.
73. 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.
74. GIESSMANN T, MAY K, MODESS C et al.: Carbamazepine regulates intestinal P-glycoprocein and multidrug resistance protein MRP2 and influences disposition of talinolol in humans. Clin. Pharmacol. Ther. (2004) 76(3):192-200.
75. 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. A review on the use of LLC-PK1 cells transfected with MDR1 genes and the different substrate specificity between species.
76. 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.
77. 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.
78. 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.
79. 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.
80. 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.
81. TIRONA RG, KIM RB: Pharmacogenomics of organic anion-transporting polypeptides (OATP). Adv. Drug Deliv. Rev. (2002) 54(10):1343-1352.
82. 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.
83. 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.
84. SAKAEDA T: MDR1 Genotype-related pharmacokinetics: fact or fiction? Drug Metab. Pharmacokinet. (2005) 20(6):391-414. A review on the contrasting data and on the relevance of P-glycoprotein polymorphism.
85. EICHELBAUM M, FROMM MF, SCHWAB M: Clinical aspects of the MDR1 (ABCB1) gene polymorphism. Ther. Drug Monit. (2004) 26(2):180-185.
86. 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.
87. 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.
88. 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.
89. 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.
90. 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.
91. 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.
92. http://www.fda.gov/oc/initiatives/criticalpath /whitepaper.html FDA US Dept of Health and Human Services. Challenge and opportunity on the critical path to new medical products. FDA (2004).
93. http://www.fda.gov/ohrms/dockets/ac/04/bri efing/2004-4079B1_04_Topic2- TabA.pdf FDA 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).
94. http://www.solvo.hu/Literature/Scientific%2 0Literature/ Scientific%20Background.html #4c The role of ABC transporters in drug resistance, metabolism and toxicity. Solvo Biotechnology (2006). Exhaustive mini review on transporters and assays by a biotechnology company specialised in ATP-binding cassette transporters.
95. http://www.bdbiosciences.com/discovery_labware/gentest/products/ transporters/transpor tocytes.shtml BD Gentest (2006).