Marked Intraindividual Variability in Antiretroviral Concentrations May Limit the Utility of Therapeutic Drug Monitoring

摘要: BACKGROUND Effective therapeutic drug monitoring for antiretrovirals requires a better understanding of intraindividual variability in pharmacokinetics. METHODS We determined concentrations human immunodeficiency virus (HIV) protease and nonnucleoside reverse-transcriptase inhibitors 10 patients with undetectable plasma HIV RNA levels who had been receiving stable regimens > or = 11 months. Plasma samples were collected at the same time day 3 times per week up to 4 Patients instructed take their every day. inhibitor using high-performance liquid chromatographic methods. Pharmacokinetic was expressed as percentage coefficient variation (ICV), which calculated patient's standard deviation divided by mean concentration that patient. RESULTS ICV 6 drugs patients, total 17 different patient-drug combinations, 600 samples. unexpectedly high most (ICVs individual taking lopinavir/ritonavir 24%, 33%, 51%, 92%; nelfinavir/M8 metabolite, they 30%/44% 39%/54%; ritonavir, 34% 43%; saquinavir, 52% 55%). ICVs lower (for efavirenz, 7%, 13%, 29%, 51%; patient nevirapine, it 25%). The median all (n 12) 43.5%, 5), 25%. CONCLUSIONS Intraindividual surprisingly virologically suppressed patients. Possible contributors include food effects, concomitant use prescription herbal medications, assay variability, medication timing, assessed self-report. High pharmacokinetic may limit utility single measurements some antiretroviral agents.