TY - JOUR
T1 - Age-related changes in plasma concentrations of the HIV protease inhibitor lopinavir
AU - Crawford, Keith W.
AU - Spritzler, John
AU - Kalayjian, Robert C.
AU - Parsons, Teresa
AU - Landay, Alan
AU - Pollard, Richard
AU - Stocker, Vicki
AU - Lederman, Michael M.
AU - Flexner, Charles
PY - 2010/6/1
Y1 - 2010/6/1
N2 - The advent of highly active antiretroviral therapy in the treatment of HIV disease has substantially extended the lifespan of individuals infected with HIV resulting in a growing population of older HIV-infected individuals. The efficacy and safety of antiretroviral agents in the population are important concerns. There have been relatively few studies assessing antiretroviral pharmacokinetics in older patients. Thirty-seven subjects aged 18-30 years and 40 subjects aged 45-79 years, naive to antiretroviral therapy, received lopinavir/ritonavir (400/100) bid, emtricitibine 200mg qd, and stavudine 40mg bid. Trough lopinavir concentrations were available for 44 subjects, collected at 24, 36, and 96 weeks. At week 24, older age was associated with higher lopinavir trough concentrations, and a trend was observed toward older age being associated with higher lopinavir trough concentrations when all time points were evaluated. In the young cohort, among subjects with two or more measurements, there was a trend toward increasing intrasubject trough lopinavir concentrations over time. Using a nonlinear, mixed-effects population pharmacokinetic model, age was negatively associated with lopinavir clearance after adjusting for adherence. Adherence was assessed by patient self-reports; older patients missed fewer doses than younger patients (p=0.02). No difference in grade 3-4 toxicities was observed between the two age group. Older patients have higher trough lopinavir concentrations and likely decreased lopinavir clearance. Age-related changes in the pharmacokinetics of antiretroviral drugs may be of increasing importance as the HIV-infected population ages and as older individuals comprise an increasing proportion of new diagnoses.
AB - The advent of highly active antiretroviral therapy in the treatment of HIV disease has substantially extended the lifespan of individuals infected with HIV resulting in a growing population of older HIV-infected individuals. The efficacy and safety of antiretroviral agents in the population are important concerns. There have been relatively few studies assessing antiretroviral pharmacokinetics in older patients. Thirty-seven subjects aged 18-30 years and 40 subjects aged 45-79 years, naive to antiretroviral therapy, received lopinavir/ritonavir (400/100) bid, emtricitibine 200mg qd, and stavudine 40mg bid. Trough lopinavir concentrations were available for 44 subjects, collected at 24, 36, and 96 weeks. At week 24, older age was associated with higher lopinavir trough concentrations, and a trend was observed toward older age being associated with higher lopinavir trough concentrations when all time points were evaluated. In the young cohort, among subjects with two or more measurements, there was a trend toward increasing intrasubject trough lopinavir concentrations over time. Using a nonlinear, mixed-effects population pharmacokinetic model, age was negatively associated with lopinavir clearance after adjusting for adherence. Adherence was assessed by patient self-reports; older patients missed fewer doses than younger patients (p=0.02). No difference in grade 3-4 toxicities was observed between the two age group. Older patients have higher trough lopinavir concentrations and likely decreased lopinavir clearance. Age-related changes in the pharmacokinetics of antiretroviral drugs may be of increasing importance as the HIV-infected population ages and as older individuals comprise an increasing proportion of new diagnoses.
UR - http://www.scopus.com/inward/record.url?scp=77954206288&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77954206288&partnerID=8YFLogxK
U2 - 10.1089/aid.2009.0154
DO - 10.1089/aid.2009.0154
M3 - Article
C2 - 20560793
AN - SCOPUS:77954206288
SN - 0889-2229
VL - 26
SP - 635
EP - 643
JO - AIDS Research and Human Retroviruses
JF - AIDS Research and Human Retroviruses
IS - 6
ER -