Factors influencing lopinavir and atazanavir plasma concentration

被引：21

作者：

Stoehr, Wolfgang ^{[1
]}

Back, David ^{[2
]}

Dunn, David ^{[1
]}

Sabin, Caroline ^{[3
]}

Winston, Alan ^{[4
]}

Gilson, Richard ^{[3
]}

Pillay, Deenan ^{[5
]}

Hill, Teresa ^{[3
]}

Ainsworth, Jonathan ^{[6
]}

Gazzard, Brian ^{[7
]}

Leen, Clifford ^{[8
]}

Bansi, Loveleen ^{[3
]}

Fisher, Martin ^{[9
,10
]}

Orkin, Chloe ^{[11
]}

Anderson, Jane ^{[12
]}

Johnson, Margaret ^{[13
]}

Easterbrook, Philippa ^{[14
]}

Gibbons, Sara ^{[2
]}

Khoo, Saye ^{[2
]}

机构：

[1] MRC, Clin Trials Unit, London NW1 2DA, England

[2] Univ Liverpool, Liverpool L69 3BX, Merseyside, England

[3] UCL, Sch Med, London W1N 8AA, England

[4] Imperial Coll Healthcare NHS Trust, London, England

[5] UCL, Dept Virol, London, England

[6] N Middlesex Univ Hosp NHS Trust, London, England

[7] Chelsea & Westminster NHS Trust, London, England

[8] Lothian Univ Hosp NHS Trust, Edinburgh, Midlothian, Scotland

[9] Brighton Univ Hosp NHS Trust, Brighton, E Sussex, England

[10] Sussex Univ Hosp NHS Trust, Brighton, E Sussex, England

[11] Barts & London NHS Trust, London, England

[12] Homerton Univ Hosp NHS Trust, London, England

[13] Royal Free NHS Trust, London, England

[14] Kings Coll Hosp London, London, England

来源：

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY | 2010年 / 65卷 / 01期

基金：

英国医学研究理事会;

关键词：

pharmacokinetics; rifabutin; drug interactions; VIRUS-INFECTED PATIENTS; REVERSE-TRANSCRIPTASE INHIBITORS; RITONAVIR-BOOSTED ATAZANAVIR; POPULATION PHARMACOKINETICS; HIV-1-INFECTED PATIENTS; ANTIRETROVIRAL THERAPY; LOPINAVIR/RITONAVIR; COMBINATION; EFAVIRENZ; TENOFOVIR;

D O I：

10.1093/jac/dkp408

中图分类号：

R51 [传染病];

学科分类号：

100401 ;

摘要：

The protease inhibitors lopinavir and atazanavir are both recommended for treatment of HIV-infected patients. Considerable inter-individual variability in plasma concentration has been observed for both drugs. The aim of this study was to evaluate which demographic factors and concomitant drugs are associated with lopinavir and atazanavir plasma concentration. Data from the Liverpool TDM (therapeutic drug monitoring) Registry were linked with the UK Collaborative HIV Cohort (CHIC) study. For each patient, the first measurement of lopinavir (twice daily) or atazanavir [once daily, ritonavir boosted (/r) or unboosted] plasma concentration was included. Linear regression was used to evaluate the association of dose, gender, age, weight, ethnicity and concomitant antiretroviral drugs or rifabutin with log-transformed drug concentration, adjusted for time since last intake. Data from 439 patients on lopinavir (69% 400 mg/r, 31% 533 mg/r; 3% concomitant rifabutin) and 313 on atazanavir (60% 300 mg/r, 32% 400 mg/r, 8% 400 mg) were included. Multivariable models revealed the following predictors for lopinavir concentration: weight (11% decrease per additional 10 kg; P = 0.001); dose (25% increase for 533 mg/r; P = 0.024); and rifabutin (116% increase; P < 0.001). For atazanavir the predictors were dose (compared with 300 mg/r: 40% increase for 400 mg/r, 67% decrease for 400 mg; overall P < 0.001) and efavirenz (32% decrease; P = 0.016) but not tenofovir (P = 0.54). This analysis confirms that efavirenz decreases atazanavir concentrations, and there was a negative association of weight and lopinavir concentrations. The strong impact of rifabutin on lopinavir concentration should be studied further.

引用

页码：129 / 137

页数：9

共 41 条

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