ADME pharmacogenetics: Investigation of the pharmacokinetics of the antiretroviral agent lopinavir coformuiated with ritonavir

Pharmacogenetics and Genomics

Volumn 20, Issue 4, 2010, Pages 217-230

  Lubomirov, Rubin ^a   Lulio, Julia Di ^a   Fayet, Aurélie ^a   Colombo, Sara ^a   Martinez, Raquel ^a   Marzolini, Catia ^c   Furrer, Hansjakob ^d   Vernazza, Pietro ^e   Calmy, Alexandra ^f   Cavassini, Matthias ^b   Ledergerber, Bruno ^h   Rentsch, Katharina ^h   Descombes, Patrick ^g   Buclin, Thierry ^a   Decosterd, Laurent A ^a   Csajka, Chantal ^a,g   Telenti, Amalio ^a  

^a LAUSANNE UNIVERSITY HOSPITAL   (Switzerland)

^b Service of Infectious Diseases   (Australia)

^c UNIVERSITY HOSPITAL BASEL   (Switzerland)

^d UNIVERSITY OF BERN   (Switzerland)

^e CANTONAL HOSPITAL ST GALLEN   (Switzerland)

^f UNIVERSITY HOSPITAL   (Switzerland)

^g UNIVERSITY OF GENEVA   (Switzerland)

^h UNIVERSITY HOSPITAL ZURICH   (Switzerland)

Author keywords

Absorption; Distribution; Lopinavir; Metabolism and excretion; Pharmacogenetics; Population pharmacokinetics

Indexed keywords

CYTOCHROME P450 3A; LOPINAVIR PLUS RITONAVIR; ORGANIC ANION TRANSPORTER 2;

ADULT; AGED; ALLELE; AREA UNDER THE CURVE; ARTICLE; BODY WEIGHT; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG CLEARANCE; FEMALE; GENETIC MODEL; GENETIC VARIABILITY; GENOTYPE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; MAJOR CLINICAL STUDY; MALE; PHARMACOGENETICS; PRIORITY JOURNAL; PROMOTER REGION; SINGLE NUCLEOTIDE POLYMORPHISM;

ADULT; AGED; AGED, 80 AND OVER; ALLELES; ANTI-HIV AGENTS; BIOLOGICAL AVAILABILITY; COHORT STUDIES; CYTOCHROME P-450 ENZYME SYSTEM; FEMALE; GENETIC ASSOCIATION STUDIES; GENETIC VARIATION; HUMANS; MALE; MIDDLE AGED; MODELS, GENETIC; MULTIDRUG RESISTANCE-ASSOCIATED PROTEINS; ORGANIC ANION TRANSPORTERS; PHARMACOGENETICS; POLYMORPHISM, SINGLE NUCLEOTIDE; PYRIMIDINONES; RITONAVIR; YOUNG ADULT;

EID: 77950787858     PISSN: 17446872     EISSN: 17446880     Source Type: Journal    
DOI: 10.1097/FPC.0b013e328336eee4     Document Type: Article

References (56)

1. Hammer SM, Eron JJ Jr, Reiss P, Schooley RT, Thompson MA, Walmsley S, et al. Antiretroviral treatment of adult HIV infection: 2008 recommendations of the International AIDS Society-USA panel. JAMA 2008; 300: 555-570.
2. 2KumarGN,JayantlV,LeeRD,WhitternDN,UchicJ,ThomasS,etal. InvitrometabolismoftheHIV-1proteaseinhibitorABT-378: speciescomparisonandmetaboliteidentification.DrugMetabDispos1999;27:86-91. (Pubitemid29061005)
3. Agarwal S, Pal D, Mitra AK. Both P-gp and MRP2 mediate transport of lopinavir, a protease Inhibitor. Int J Pharm 2007; 339: 139-147. (Pubitemid 46977600)
4. King JR, Wynn H, Brundage R, Acosta EP. Pharmacokinetic enhancement of protease inhibitor therapy. Clin Pharmacokinet 2004; 43: 291-310. (Pubitemid 38534753)
5. Molto J, Blanco A, Miranda C, Miranda J, Puig J, Valle M, et al. Variability in non-nucleoside reverse transcriptase and protease inhibitor concentrations among HIV-infected adults in routine clinical practice. Br J Clin Pharmacol 2006; 62: 560-566. (Pubitemid 44571577)
6. Van der Leur MR, Burger DM, Ia Porte CJ, Koopmans PP. A retrospective TDM database analysis of interpatlent variability in the pharmacokinetics of lopinavlr in HIV-infected adults. Ther Drug Monk 2006; 28: 650-653.
7. Colombo S, Buclin T, Decosterd LA, Telenti A, Furrer H, Lee BL, et al. Orosomucoid (alphal -acid glycoprotein) plasma concentration and genetic variants: effects on human immunodeficiency virus protease inhibitor clearance and cellular accumulation. Clin Pharmacol Ther 2006; 80: 307-318. (Pubitemid 44479747)
8. Jullien V, Urien S, Hirt D, Delaugerre C, Rey E, Teglas JP, et al. Population analysis of weight-, age-, and sex-related differences in the pharmacokinetics of lopinavir in children from birth to 18 years. Antimicroh Agents Chemother 2006; 50: 3548-3555. (Pubitemid 44684864)
9. Molto J, Barbanoj MJ, Miranda C, Blanco A, Santos JR, Negredo E, et al. Simultaneous population pharmacokinetic model for lopinavir and ritonavir in HIV-infected adults. Clin Pharmacokinet 2008; 47: 681-692.
10. Peng JZ, Pulido F, Causemaker SJ, LI J, Lorenzo A, Cepeda C, et al. Pharmacokinetics of lopinavir/ritonavlr in HIV/hepatltis C virus-coinfected subjects with hepatic impairment. J Clin Pharmacol 2006; 46: 265-274. (Pubitemid 43260313)
11. Stek AM, Mirochnick M, Capparelli E, Best BM, Hu C, Burchett SK, et al. Reduced lopinavir exposure during pregnancy. AIDS 2006; 20: 1931-1939.
12. Estrela RC, Santoro AB, Barroso PF, Tuyama M, Suarez-Kurtz G. CYP3A5 genotype has no impact on plasma trough concentrations of lopinavir and ritonavir in HIV-infected subjects. Clin Pharmacol Ther 2008; 84: 205-207.
13. Estrela RC, Ribeiro FS, Barroso PF, Tuyama M, Gregorio SP, Dias-Neto E, et al. ABCB1 polymorphisms and the concentrations of lopinavir and ritonavir in blood, semen and saliva of HIV-infected men under antiretroviral therapy. Pharmacogenomics 2009; 10: 311-318.
14. Gupta SK, Rosenkranz SL, Cramer YS, Koletar SL, Szczech LA, Amorosa V, et al. The pharmacokinetics and pharmacogenomics of efavirenz and lopinavir/ritonavir in HIV-infected persons requiring hemodialysis. AIDS 2008; 22: 1919-1927.
15. Ma Q, Brazeau D, Zingman BS, Reichman RC, Fischl MA, Gripshover BM, et al. Multidrug resistance 1 polymorphisms and trough concentrations of atazanavir and lopinavir in patients with HIV. Pharmacogenomics 2007; 8: 227-235. (Pubitemid 46477734)
16. Winzer R, Langmann P, Zilly M, Tollmann F, Schubert J, Klinker H, et al. No influence of the P-glycoprotein genotype (MDR1 C3435T) on plasma levels of lopinavir and efavirenz during antiretroviral treatment. Eur J Med Res 2003; 8: 531-534.
17. Wyen C, Fuhr U, Frank D, Aarnoutse RE, Klaassen T, Lazar A, et al. Effect of an antiretroviral regimen containing ritonavir boosted lopinavlr on intestinal and hepatic CYP3A, CYP2D6 and P-glycoprotein in HIV-infected patients. Clin Pharmacol Ther 2008; 84: 75-82. (Pubitemid 351861487)
18. Frazer KA, Ballinger DG, Cox DR, Hinds DA, Stuve LL, Gibbs RA, et al. A second generation human haplotype map of over 3.1 million SNPs. Wafure 2007; 449: 851-861.
19. Colombo S, Beguin A, Telenti A, Biollaz J, Buclin T, Rochat B, et al. Intracellular measurements of anti-HIV drugs indinavir, amprenavir, saquinavir, ritonavir, nelfinavir, lopinavir, atazanavir, efavirenz and nevirapine in peripheral blood mononuclear cells by liquid chromatography coupled to tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2005; 819: 259-276. (Pubitemid 40521961)
20. Fayet A, Beguin A, de Tejada BM, Colombo S, Cavassini M, Gerber S, et al. Determination of unbound antiretroviral drug concentrations by a modified ultrafiltration method reveals high variability in the free fraction. Ther Drug Monit 2008; 30: 511-522.
21. Lubomirov R, Csajka C, Telenti A. ADME pathway approach for pharmacogenetic studies of anti-HIV therapy. Pharmacogenomics 2007; 8: 623-633. (Pubitemid 46939587)
22. De Bakker Pl, Yelensky R, Pe'er I, Gabriel SB, Daly MJ, Altshuler D. Efficiency and power in genetic association studies. War Genet 2005; 37: 1217-1223.
23. Eberle MA, Ng PC, Kuhn K, Zhou L, Peiffer DA, Galver L, et al. Power to detect risk alleles using genome-wide tag SNP panels. PLoS Genet 2007; 3: 1827-1837. (Pubitemid 350072049)
24. Peters EJ, McLeod HL. Ability of whole-genome SNP arrays to capture 'must have' pharmacogenomic variants. Pharmacogenomics 2008; 9: 1573-1577.
25. Yuan HY, Chiou JJ, Tseng WH, Liu CH, Liu CK, Lin YJ, et al. FASTSNP: an always up-to-date and extendable service for SNP function analysis and prioritization. Nucleic Acids Res 2006; 34: W635-W641.
26. Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, Hunter DJ, et al. Finding the missing heritablllty of complex diseases. Nature 2009; 461: 747-753.
27. Stephens M, Smith NJ, Donnelly P. A new statistical method for haplotype reconstruction from population data. Am J Hum Genet 2001 ; 68: 978-989. (Pubitemid 32289743)
28. Stephens M, Donnelly P. A comparison of bayesian methods for haplotype reconstruction from population genotype data. Am J Hum Genet 2003; 73: 1162-1169. (Pubitemid 37414228)
29. Kumar S, Nei M, Dudley J, Tamura K. MEGA: a biologist-centric software for evolutionary analysis of DNA and protein sequences. Brief Bioinform 2008; 9: 299-306. (Pubitemid 351890826)
30. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 2007; 81: 559-575. (Pubitemid 47330214)
31. Balding DJ. A tutorial on statistical methods for population association studies. Nat Rev Genet 2006; 7: 781-791. (Pubitemid 44413222)
32. KameyamaY,YamashitaK,KobayashiK,HosokawaM,ChibaK. FunctionalcharacterizationofSLCO1B1(OATP-C)variants,SLCO1B1*5,SLCO 1B1*15andSLCO1B1*15+C1007G, byusingtransientexpressionsystemsofHeLaandHEK293cells.PharmacogenetGenomics2005; 15:513-522.(Pubitemid41017600)
33. Konig J, Seithel A, Gradhand U, Fromm MF. Pharmacogenomics of human OATP transporters. Naunyn Schmiedebergs Arch Pharmacol 2006; 372: 432-443.
34. Niemi M. Role of OATP transporters in the disposition of drugs. Pharmacogenomics 2007; 8: 787-802. (Pubitemid 47288978)
35. Tirona RG, Leake BF, Merino G, Kim RB. Polymorphisms in OATP-C: identification of multiple allelic variants associated with altered transport activity among European- and African-Americans. J Biol Chem 2001 ; 276: 35669-35675. (Pubitemid 37384369)
36. Badagnani I, Castro RA, Taylor TR, Brett CM, Huang CC, Stryke D, et al. Interaction of methotrexate with organic-anion transporting polypeptide 1A2 and Its genetic variants. J Pharmacol Exp Ther 2006; 318: 521-529. (Pubitemid 44061225)
37. Pahl R, Schafer H, Muller HH. Optimal multistage deslgns-a general framework for efficient genome-wide association studies. Biostatistics 2009; 10: 297-309.
38. Haenisch S, Zimmermann U, Dazert E, Wruck CJ, Dazert P, Siegmund W, et al. Influence of polymorphisms of ABCB1 and ABCC2 on mRNA and protein expression in normal and cancerous kidney cortex. Pharmacogenomics J 2007; 7: 56-65. (Pubitemid 46322080)
39. Hartkoorn RC, Kwan WS, Shallcross V, Chaikan A, Liptrott N, Egan D, et al. HIV protease inhibitors are substrates for OATP1A2, OATP1B1 and OATP1B3 and lopinavir plasma concentrations are influenced by SLCO1B1 polymorphisms. Pharmacogenetics and Genomics 2010; 20: 112-120.
40. Niemi M. High plasma pravastatin concentrations are associated with single nucleotide polymorphisms and haplotypes of organic anion transporting polypeptide-C (OATP-C, SLCO1B1). Pharmacogenetics 2004; 14: 429-440. (Pubitemid 38971233)
41. Nishizato Y, Ieiri I, Suzuki H, Kimura M, Kawabata K, Hirota T, et al. Polymorphisms of OATP-C (SLC21A6) and OAT3 (SLC22A8) genes: consequences for pravastatin pharmacokinetics. Clin Pharmacol Ther 2003; 73: 554-565. (Pubitemid 37249126)
42. Michalski C, Cui Y, Nies AT, Nuessler AK, Neuhaus P, Zanger UM, et al. A naturally occurring mutation in the SLC21A6 gene causing impaired membrane localization of the hepatocyte uptake transporter. J Biol Chem 2002; 277: 43058-43063. (Pubitemid 35285687)
43. Janneh O, Jones E, Chandler B, Owen A, Khoo SH. Inhibition of P-glycoprotein and multidrug resistance-associated proteins modulates the intracellular concentration of lopinavir in cultured CD4T cells and primary human lymphocytes. J Antimicrob Chemother 2007; 60: 987-993. (Pubitemid 47617744)
44. Huisman MT, Smit JW, Crommentuyn KM, Zelcer N, Wiltshire HR, Beijnen JH, et al. Multidrug resistance protein 2 (MRP2) transports HIV protease inhibitors, and transport can be enhanced by other drugs. AIDS 2002; 16: 2295-2301. (Pubitemid 35449015)
45. Dussault I, Lin M, Hollister K, Wang EH, Synold TW, Forman BM. Peptide mimetic HIV protease inhibitors are ligands for the orphan receptor SXR. J Biol Chem 2001 ; 276: 33309-33312. (Pubitemid 37384536)
46. Haenisch S, May K, Wegner D, Caliebe A, Cascorbi I, Siegmund W. Influence of genetic polymorphisms on intestinal expression and rifampicintype induction of ABCC2 and on bioavailability of talinolol. Pharmacogenet Genomics 2008; 18: 357-365. (Pubitemid 351367529)
47. Zhou Q, Sparreboom A, Tan EH, Cheung YB, Lee A, Poon D, et al. Pharmacogenetic profiling across the irlnotecan pathway in Asian patients with cancer. Br J Clin Pharmacol 2005; 59: 415-424. (Pubitemid 40523885)
48. Naesens M, Kuypers DR, Verbeke K, Vanrenterghem Y. Multidrug resistance protein 2 genetic polymorphisms influence mycophenollc acid exposure in renal allograft recipients. Transplantation 2006; 82: 1074-1084. (Pubitemid 44632124)
49. Rau T, Erney B, Gores R, Eschenhagen T, Beck J, Langer T. High-dose methotrexate in pediatric acute lymphoblastic leukemia: impact of ABCC2 polymorphisms on plasma concentrations. Clin Pharmacol Ther 2006; 80: 468-476. (Pubitemid 44737489)
50. Anderson PL, Lamba J, Aqullante CL, Schuetz E, Fletcher CV. Pharmacogenetlc characteristics of indinavir, zidovudine, and lamivudine therapy In HIV-infected adults: a pilot study. J Acquir Immune Defic Syndr 2006; 42: 441-449. (Pubitemid 44050891)
51. Kiser JJ, Carten ML, Aquilante CL, Anderson PL, Wolfe P, King TM, et al. The effect of lopinavlr/rltonavir on the renal clearance of tenofovir in HIV-infected patients. Clin Pharmacol Ther 2008; 83: 265-272.
52. Crommentuyn KM, Kappelhoff BS, Mulder JW, Mairuhu AT, van Gorp EC, Meenhorst PL, et al. Population pharmacokinetics of lopinavir in combination with ritonavir in HIV-1-infected patients. Br J Clin Pharmacol 2005; 60: 378-389. (Pubitemid 41428469)
53. Hsu A, Isaacson J, Brun S, Bernstein B, Lam W, Bertz R, et al. Pharmacokinetic-pharmacodynamic analysis of lopinavir-ritonavir in combination with efavirenz and two nucleoside reverse transcriptase inhibitors In extensively pretreated human immunodeficiency virus-infected patients. Antimicrob Agents Chemother 2003; 47: 350-359. (Pubitemid 36070384)
54. Marzolini C, Tirana RG, Lee W, Gervasini G, Ho RH, Leake B, et al. Unexpected complexity in nuclear receptor activation by HIV protease inhibitors and induction of CYP enzymes and transporters. In: 11th Conference on Retroviruses and Opportunistic Infections, Feb 2004, San Francisco, Abstract 135 2009.
55. Mauss S, Schmutz G, Kuschak D. Unfavourable interaction of amprenavir and lopinavir in combination with ritonavir? AIDS 2002; 16: 296-297. (Pubitemid 34118580)
56. Arab-Alameddine M, Di IJ, Buclin T, Rotger M, Lubomirov R, Cavassini M, et al. Pharmacogenetics-based population pharmacokinetic analysis of efavirenz in HIV-1-infected individuals. Clin Pharmacol Ther 2009; 85: 485-494.