Pharmacokinetics of indinavir and nelfinavir in treatment-naive, human immunodeficiency virus-infected subjects.
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, <10 to 949 ng/ml; one subject had a concentration of <10 ng/ml), and the concentration 8 h after administration of the study dose was 159 ng/ml (range, 85 to 506 ng/ml). In the group receiving 1000 mg of indinavir every 12 h with nelfinavir (n = 10), the median indinavir C(0) was <10 ng/ml (range, <10 to 3740 ng/ml; six subjects had a value of <10 ng/ml), and the C(12 h) was 44 ng/ml (range, <10 to 4236 ng/ml; five subjects had a value of <10 ng/ml), while the subjects who received 1200 mg of indinavir every 12 h with nelfinavir (n = 7) had a C(0) of 146 ng/ml (range, 58 to 5215 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, <187.5 to 4579 ng/ml), and the C(12 h) was 1554 ng/ml (range, <187.5 to 5,540 ng/ml). Due to the unacceptable number of undetectable indinavir trough concentrations, 1200 mg of indinavir appears to be the preferred dose in a twice-daily regimen that includes nelfinavir.
DiCenzo
Robert
R
University at Buffalo, Buffalo, New York 14260, USA.
Forrest
Alan
A
Fischl
Margaret A
MA
Collier
Ann
A
Feinberg
Judith
J
Ribaudo
Heather
H
DiFrancecso
Robin
R
Morse
Gene D
GD
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D015153:Blotting, Western; D005260:Female; D015658:HIV Infections / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D019469:Indinavir / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D019888:Nelfinavir / Q000008:administration & dosage / Q000493:pharmacokinetics*
D019380:Anti-HIV Agents; D019469:Indinavir; D019888:Nelfinavir