Pharmacokinetics of Indinavir and Nelfinavir in Treatment-Naive, Human Immunodeficiency Virus-Infected Subjects

Open Access
Publisher Website
Google Scholar
Abstract
AIDS Clinical Trials Group protocol 388 was designed to compare a three-drug regimen (indinavir with dual nucleosides) to a four-drug regimen (indinavir plus nelfinavir or indinavir plus efavirenz with dual nucleosides). Blood samples from patients taking indinavir and nelfinavir were collected over 8 to 12 h following a specified dose and were analyzed with high-performance liquid chromatography. Pharmacokinetic data were derived by using noncompartmental analysis. Following administration of indinavir every 8 h in the absence of nelfinavir ( n = 8), the median predose indinavir concentration ( C 0 ) was 369 ng/ml (range, n = 10), the median indinavir C 0 was C 12 h was 44 ng/ml (range, n = 7) had a C 0 of 146 ng/ml (range, 58 to 5,215 ng/ml) and a C 12 h of 95 ng/ml (range, 12 to 954 ng/ml). Indinavir clearance was significantly lower in the presence of nelfinavir (median [interquartile range], 34.1 liters/h [range, 22.6 to 45.8 liters/h] versus 47.9 liters/h [range, 42.7 to 70.3 liters/h]; P < 0.017). For subjects receiving 1,000 mg of indinavir every 12 h, the median C 0 value for nelfinavir ( n = 9) was 1,779 ng/ml (range, C 12 h was 1,554 ng/ml (range, <187.5 to 5,540 ng/ml). Due to the unacceptable number of undetectable indinavir trough concentrations, 1,200 mg of indinavir appears to be the preferred dose in a twice-daily regimen that includes nelfinavir.

This publication has 12 references indexed in Scilit: