Clinical pharmacokinetics and summary of efficacy and tolerability of atazanavir

被引:127
作者
Le Tiec, C
Barrail, A
Goujard, U
Taburet, AM
机构
[1] Hop Bicetre, Assistance Publ Hop Paris, Dept Clin Pharm, F-94270 Le Kremlin Bicetre, Paris, France
[2] Hop Bicetre, Assistance Publ Hop Paris, Dept Internal Med, F-94270 Le Kremlin Bicetre, Paris, France
关键词
D O I
10.2165/00003088-200544100-00003
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The efficacy of HIV-1 protease inhibitors (Pls) as part of highly active antiretroviral therapy is now well established and has provided benefits to many patients with HIV infection. Atazanavir is a new azapeptide PI compound that was recently approved in the US and Europe. Atazanavir is recommended in combination with other antiretroviral agents for the treatment of HIV-1 infection. Atazanavir is rapidly absorbed and administration of a single dose of atazanavir with a light meal resulted in a 70% increase in area under the plasma concentration-time curve (AUC); therefore atazanavir should be taken with food. Atazanavir is 86% bound to human serum protein independently of concentration. Concentration in body fluids appeared to be lower than plasma concentration. Like other Pls, atazanavir is extensively metabolised by hepatic cytochrome P450 (CYP) 3A isoenzymes. The mean terminal elimination half-life in healthy volunteers was approximately 7 hours at steady state following administration of atazanavir 400mg daily with a light meal. When atazanavir 300mg was coadministered with ritonavir 100mg on a once-daily dosage regimen, atazanavir AUC from 0 to 24 hours and minimum plasma concentration were increased by 3- to 4-fold and approximately 10-fold, respectively, compared with atazanavir 300mg alone. Therefore, ritonavir boosted atazanavir regimen (ritonavir 100mg and atazanavir 300mg once daily) is increasingly favoured in some patients. Efavirenz, a potent CYP3A inducer, decreased atazanavir concentrations by 75% and, unexpectedly, tenofovir, a nucleotide reverse transcriptase inhibitor, decreased atazanavir concentrations by 25%. Average predose concentrations in HIV-infected patients who received atazanavir 400mg once daily were 273 ng/mL, which was believed to be several-fold higher than protein-binding corrected 50% inhibitory concentration of wildtype viruses. In HIV-infected patients who received once-daily ritonavir (100mg) boosted atazanavir (300mg), mean (+/- SD) trough concentration was 862 (+/- 838) ng/mL. Several clinical trials showed the efficacy of atazanavir 400mg once daily with a nucleoside analogue backbone in antiretroviral-naive patients. The atazanavir 300/ritonavir 100mg once-daily combination coadministered with other antiretrovirals showed the efficacy of this strategy in patients receiving efavirenz or in moderately antiretroviral-experienced HIV-infected patients. Recommended once-daily doses of atazanavir taken with food are either 400mg or 300mg in combination with low dose ritonavir (100mg) in moderately antiretroviral-experienced patients. Major advantages of atazanavir to date are its simplicity of administration (once-daily administration) and its less undesirable effect on the lipid profiles in patients.
引用
收藏
页码:1035 / 1050
页数:16
相关论文
共 78 条
[1]   Therapeutic drug monitoring - An aid to optimising response to antiretroviral drugs? [J].
Aarnoutse, RE ;
Schapiro, JM ;
Boucher, CAB ;
Hekster, YA ;
Burger, DM .
DRUGS, 2003, 63 (08) :741-753
[2]  
AGARWALA S, 2001, 8 C RETR OPP INF 200
[3]  
AGARWALA S, 2002, 42 INT C ANT AG CHEM
[4]  
AGARWALA S, 2002, 9 C RETR OPP INF FEB
[5]  
[Anonymous], GUID US ANT AG HIV 1
[6]   Pharmacokinetic drug interactions with nevirapine [J].
Back, D ;
Gibbons, S ;
Khoo, S .
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, 2003, 34 :S8-S14
[7]   Therapeutic drug monitoring in HIV infection: current status and future directions [J].
Back, D ;
Gatti, G ;
Fletcher, C ;
Garaffo, R ;
Haubrich, R ;
Hoetelmans, R ;
Kurowski, M ;
Luber, A ;
Merry, C ;
Perno, CF .
AIDS, 2002, 16 :S5-S37
[8]   Grapefruit juice-drug interactions [J].
Bailey, DG ;
Malcolm, J ;
Arnold, O ;
Spence, JD .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 1998, 46 (02) :101-110
[9]  
BARRIOS A, 11 C RETR OPP INF SA
[10]   Pharmacokinetics and potential interactions amongst antiretroviral agents used to treat patients with HIV infection [J].
Barry, M ;
Mulcahy, F ;
Merry, C ;
Gibbons, S ;
Back, D .
CLINICAL PHARMACOKINETICS, 1999, 36 (04) :289-304