Integration of absorption, distribution, metabolism, and elimination genotyping data into a population pharmacokinetic analysis of nevirapine

Pharmacogenetics and Genomics

Volumn 21, Issue 11, 2011, Pages 721-730

  Lehr, Thorsten ^a   Yuan, Jing ^c   Hall, David ^d   Zimdahl Gelling, Heike ^b   Schaefer, Hans Guenter ^a   Staab, Alexander ^a   MacGregor, Thomas R ^e   Jayadev, Supriya ^c,f  

^a Translational Medicine   (Germany)

^b BOEHRINGER INGELHEIM PHARMA GMBH AND CO KG   (Germany)

^c Non Clinical Drug Safety   (United States)

^d Clinical Biostatistics   (United States)

^e Translational Medicine   (United States)

^f BOEHRINGER INGELHEIM PHARMACEUTICALS INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOCHROME P450 2B6; CYTOCHROME P450 2C19; EFAVIRENZ; LAMIVUDINE; NEVIRAPINE; STAVUDINE;

ADULT; ALLELE; ARTICLE; ASIAN; CAUCASIAN; CONTROLLED STUDY; DATA ANALYSIS; DATA ANALYSIS SOFTWARE; DIAGNOSTIC IMAGING; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DISPOSITION; DRUG DISTRIBUTION; DRUG ELIMINATION; DRUG EXPOSURE; DRUG METABOLISM; FEMALE; GENE; GENETIC LINKAGE; GENETIC VARIABILITY; GENOTYPE; HETEROZYGOTE; HISPANIC; HUMAN; HUMAN TISSUE; INFORMED CONSENT; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY; PHARMACOKINETICS; POPULATION GENETICS; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SINGLE NUCLEOTIDE POLYMORPHISM;

EID: 84860411455     PISSN: 17446872     EISSN: 17446880     Source Type: Journal    
DOI: 10.1097/FPC.0b013e32834a522e     Document Type: Article

References (41)

1. Lehr T, Staab A, Schaefer HG. Biosimulation in clinical drug development. In:Bertau M, Mosekilde E, Westerhoff H, editors. Biosimulation in drug development. 2008; Weinheim: Wiley. pp. 447-484.
2. Lehr T, Schaefer HG, Staab A. Integration of high-throughput genotyping data into pharmacometric analyses using non-linear mixed effects modeling.Pharmacogenet Genomics 2010; 20:442-450.
3. Lamson MJ, Sabo JP, MacGregor TR, Pav JW, Rowland L, Hawi A, et al.Single dose pharmacokinetics and bioavailability of nevirapine in healthy volunteers. Biopharm Drug Dispos 1999; 20:285-291.
4. Yazdanian M, Ratigan M, Joseph D, Silverstein M, Riska P, Johnstone JN, et al. Nevirapine, a non-nucleoside RT inhibitor, readily permeates the blood brain barrier. 4th Conf on Retroviruses and Opportunistic Infections, Washington, 22-26 January 1997 (Poster No.567). 1997.
5. Riska P, Lamson M, MacGregor T, Sabo J, Hattox S, Pav J, et al. Disposition and biotransformation of the antiretroviral drug nevirapine in humans. Drug Metab Dispos 1999; 27:895-901.
6. Lamson M, MacGregor T, Riska P, Erickson D, Maxfield P, Rowland L, et al. Nevirapine induces both CYP3A4 and CYP2B6 metabolic pathways. ClinPharmacol Ther 1999; 65:137.
7. Kappelhoff BS, Van Leth F, MacGregor TR, Lange JMA, Beijnen JH, Huitema ADR. Nevirapine and efavirenz pharmacokinetics and covariate analysis inthe 2NN study. Antivir Ther 2005; 10:145-155.
8. Van Leth F, Phanuphak P, Ruxrungtham K, Baraldi E, Miller S, Gazzard B, et al. Comparison of first-line antiretroviral therapy with regimens includingnevirapine, efavirenz, or both drugs, plus stavudine and lamivudine: a randomised open-label trial, the 2NN Study. Lancet 2004; 363:1253-1263.
9. Saitoh A, Sarles E, Capparelli E, Aweeka F, Kovacs A, Burchett SK, et al.CYP2B6 genetic variants are associated with nevirapine pharmacokinetics and clinical response in HIV-1-infected children. AIDS 2007; 21:2191-2199.
10. Penzak SR, Kabuye G, Mugyenyi P, Mbamanya F, Natarajan V, Alfaro RM,et al. Cytochrome P450 2B6 (CYP2B6) G516T influences nevirapineplasma concentrations in HIV-infected patients in Uganda. HIV Med 2007; 8:86-91.
11. Rotger M, Colombo S, Furrer H, Bleiber G, Buclin T, Lee BL, et al. Influence of CYP2B6 polymorphism on plasma and intracellular concentrations and toxicity of efavirenz and nevirapine in HIV-infected patients. Pharmacogenet Genomics 2005; 15:1-5.
12. Wyen C, Hendra H, Vogel M, Hoffmann C, Knechten H, Brockmeyer NH, et al. Impact of CYP2B6 983T ≥C polymorphism on non-nucleoside reverse transcriptase inhibitor plasma concentrations in HIV-infected patients. J Antimicrob Chemother 2008; 61:914-918.
13. Chou M, Bertrand J, Segeral O, Verstuyft C, Borand L, Comets E, et al.Population pharmacokinetic-pharmacogenetic study of nevirapine in HIVinfectedCambodian patients. Antimicrob Agents Chemother 2010; 54:4432-4439.
14. Parke J, Holford NHG, Charles BG. A procedure for generating bootstrap samples for the validation of nonlinear mixed-effects population models. Comput Methods Programs Biomed 1999; 59:19-29.
15. Ette EI. Stability and performance of a population pharmacokinetic model. J Clin Pharmacol 1997; 37:486-495.
16. Lindbom L, Ribbing J, Jonsson EN. Perl-speaks-NONMEM (PsN) - a Perl module for NONMEM related programming. Comput Methods Programs Biomed 2004; 75:85-94.
17. Beal SL, Sheiner LB. NONMEM users guides. San Francisco: University of California. 1998.
18. Akaike H. A new look at the statistical model identification. IEEE Trans Automatic Control 1974; 19:716-723.
19. Jonsson EN, Karlsson MO. Xpose - An S-PLUS based populationpharmacokinetic/pharmacodynamic model building aid for NONMEM.Comput Methods Programs Biomed 1999; 58:51-64.
20. Karlsson MO, Savic RM. Diagnosing model diagnostics. Clin PharmacolTher 2007; 82:17-20.
21. Lang T, Klein K, Fischer J, Nuessler AK, Neuhaus P, Hofmann U, et al. Extensive genetic polymorphism in the human CYP2B6 gene with impact on expression and function in human liver. Pharmacogenetics 2001; 11: 399-415.
22. Nyakutira C, Röshammar D, Chigutsa E, Chonzi P, Ashton M, Nhachi C, et al. High prevalence of the CYP2B6 516G- T(.*6) variant and effect on the population pharmacokinetics of efavirenz in HIV/AIDS outpatients in Zimbabwe. Eur J Clin Pharmacol 2008; 64:357-365.
23. Lang T, Klein K, Richter T, Zibat A, Kerb R, Eichelbaum M, et al. Multiple novel nonsynonymous CYP2B6 gene polymorphisms in Caucasians: demonstration of phenotypic null alleles. J Pharmacol Exp Ther 2004; 311:34-43.
24. Schipani A, Wyen C, Mahungu T, Hendra H, Egan D, Siccardi M, et al. Integration of population pharmacokinetics and pharmacogenetics: an aid to optimal nevirapine dose selection in HIV-infected individuals. J Antimicrob Chemother 2011; 66:1332-1339.
25. Klein K, Lang T, Saussele T, Barbosa-Sicard E, Schunck WH, Eichelbaum M, et al. Genetic variability of CYP2B6 in populations of African and Asian origin: Allele frequencies, novel functional variants, and possible implications for anti-HIV therapy with efavirenz. Pharmacogenet Genomics 2005; 15:861-873.
26. Mehlotra RK, Bockarie MJ, Zimmerman PA. CYP2B6 983T ≥C polymorphism is prevalent in West Africa but absent in Papua New Guinea: Implications for HIV/AIDS treatment. Br J Clin Pharmacol 2007; 64: 391-395.
27. Rotger M, Tegude H, Colombo S, Cavassini M, Furrer H, Dé costerd L, et al. Predictive value of known and novel alleles of CYP2B6 for efavirenz plasma concentrations in HIV-infected individuals. Clin Pharmacol Ther 2007; 81:557-566.
28. Carr DF, La Porte CJ, Pirmohamed M, Owen A, Cortes CP. Haplotype structure of CYP2B6 and association with plasma efavirenz concentrations in a Chilean HIV cohort. J Antimicrob Chemother 2010; 65:1889-1893.
29. De Morais SMF, Wilkinson GR, Blaisdell J, Nakamura K, Meyer UA, Goldstein JA. The major genetic defect responsible for the polymorphism of S-mephenytoin metabolism in humans. J Biol Chem 1994; 269: 15419-15422.
30. Ibeanu GC, Goldstein JA, Meyer U, Benhamou S, Bouchardy C, Dayer P, et al. Identification of new human CYP2C19 alleles (CYP2C196 and CYP2C192B) in a Caucasion poor metabolizer of mephenytoin. J Pharmacol Exp Ther 1998; 286:1490-1495.
31. Desta Z, Zhao X, Shin JG, Flockhart DA. Clinical significance of the cytochrome P450 2C19 genetic polymorphism. Clin Pharmacokinet 2002; 41:913-958.
32. Damle BD, Uderman H, Biswas P, Crownover P, Lin C, Glue P. Influence of CYP2C19 polymorphism on the pharmacokinetics of nelfinavir and its active metabolite. Br J Clin Pharmacol 2009; 68:682-689.
33. Zandvliet AS, Huitema ADR, Copalu W, Yamada Y, Tamura T, Beijnen JH, et al. CYP2C9 and CYP2C19 polymorphic forms are related to increased indisulam exposure and higher risk of severe hematologic toxicity. Clin Cancer Res 2007; 13:2970-2976.
34. Skowron G, Leoung G, Hall DB, Robinson P, Lewis R, Grosso R, et al. Pharmacokinetic evaluation and short-term activity of stavudine, nevirapine, and nelfinavir therapy in HIV-1-infected adults. J Acquir Immune Defic Syndr 2004; 35:351-358.
35. Hirani VN, Raucy JL, Lasker JM. Conversion of the HIV protease inhibitor nelfinavir to a bioactive metabolite by human liver CYP2C19. Drug Metab Dispos 2004; 32:1462-1467.
36. Wen B, Chen Y, Fitch WL. Metabolic activation of nevirapine in human liver microsomes: dehydrogenation and inactivation of cytochrome P450 3A4. Drug Metab Dispos 2009; 37:1557-1562.
37. Li-Wan-Po A, Girard T, Farndon P, Cooley C, Lithgow J. Pharmacogenetics of CYP2C19: functional and clinical implications of a new variant CYP2C19.*17. Br J Clin Pharmacol 2010; 69:222-230.
38. Bjornsson TD, Wagner JA, Donahue SR, Harper D, Karim A, Khouri MS, et al. A review and assessment of potential sources of ethnic differences in drug responsiveness. J Clin Pharmacol 2003; 43:943-967.
39. Wood AJJ, Zhou HH. Ethnic differences in drug disposition and responsiveness. Clin Pharmacokinet 1991; 20:350-373.
40. Johnson JA. Influence of race or ethnicity on pharmacokinetics of drugs. J Pharm Sci 1997; 86:1328-1333.
41. Kim K, Johnson JA, Derendorf H. Differences in drug pharmacokinetics between East Asians and Caucasians and the role of genetic polymorphisms. J Clin Pharmacol 2004; 44:1083-1105.