Antiviral effect and pharmacokinetic interaction between nevirapine and indinavir in persons infected with human immunodeficiency virus type 1.
Nevirapine and indinavir have the potential of affecting the pharmacokinetics of each other. In a prospective trial, 24 human immunodeficiency virus (HIV)-infected subjects on stable nucleoside or no therapy were treated with 800 mg of indinavir every 8 h. After 7 days, 200 mg of nevirapine a day was added for 14 days and then increased to 200 mg twice a day. At day 7 (before nevirapine), there was a sevenfold difference among the subjects in indinavir area under the curve (AUC), and there was a significant correlation between indinavir AUC (r2=0.378, P=.019), minimum plasma concentration (Cmin; r2=0.359, P=.023), maximum plasma concentration (Cmax; r2=0.340, P=.028), and plasma HIV RNA decline. Nevirapine significantly reduced median indinavir Cmin (47.5%) and AUC (27.4%) and, to a lesser extent, Cmax (11%). Plasma HIV RNA values were </=20 copies/mL in 10 of 17 (58.8%) subjects at 58 weeks or last visit. These data suggest that indinavir dosing should be dependent on drug exposure and not on cotherapy with nevirapine.
Murphy
R L
RL
Division of Infectious Diseases, Department of Medicine,Northwestern University, Chicago, IL 60611, USA. r-murphy@nwu.edu
Sommadossi
J P
JP
Lamson
M
M
Hall
D B
DB
Myers
M
M
Dusek
A
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D018791:CD4 Lymphocyte Count; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D019469:Indinavir / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D019829:Nevirapine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019469:Indinavir; D019829:Nevirapine