Pharmacokinetics of ritonavir and delavirdine in human immunodeficiency virus-infected patients.
To evaluate the pharmacokinetic effect of adding delavirdine mesylate to the antiretroviral regimens of human immunodeficiency virus (HIV)-infected patients stabilized on a full dosage of ritonavir (600 mg every 12 h), 12 HIV-1-infected subjects had delavirdine mesylate (400 mg every 8 h) added to their current antiretroviral regimens for 21 days. Ritonavir pharmacokinetics were evaluated before (day 7) and after (day 28) the addition of delavirdine, and delavirdine pharmacokinetics were evaluated on day 28. The mean values (+/- standard deviations) for the maximum concentration in serum (C(max)) of ritonavir, the area under the concentration-time curve from 0 to 12 h (AUC(0-12)), and the minimum concentration in serum (C(min)) of ritonavir before the addition of delavirdine were 14.8 +/- 6.7 micro M, 94 +/- 36 micro M. h, and 3.6 +/- 2.1 micro M, respectively. These same parameters were increased to 24.6 +/- 13.9 micro M, 154 +/- 83 micro M. h, and 6.52 +/- 4.85 micro M, respectively, after the addition of delavirdine (P is <0.05 for all comparisons). Delavirdine pharmacokinetic parameters in the presence of ritonavir included a C(max) of 23 +/- 16 micro M, an AUC(0-8) of 114 +/- 75 micro M. h, and a C(min) of 9.1 +/- 7.5 micro M. Therefore, delavirdine increases systemic exposure to ritonavir by 50 to 80% when the drugs are coadministered.
Shelton
Mark J
MJ
Laboratory for Antiviral Research, Department of Pharmacy Practice, University at Buffalo, New York, USA.
Hewitt
Ross G
RG
Adams
John
J
Della-Coletta
Andrew
A
Cox
Steven
S
Morse
Gene D
GD
D000328:Adult; D019380:Anti-HIV Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000502:physiology; D019389:Cytochrome P-450 CYP2D6 / Q000502:physiology; D051544:Cytochrome P-450 CYP3A; D020008:Delavirdine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010089:Oxidoreductases, N-Demethylating / Q000502:physiology; D019438:Ritonavir / Q000008:administration & dosage / Q000493:pharmacokinetics*
D019380:Anti-HIV Agents; D020008:Delavirdine; D001189:Aryl Hydrocarbon Hydroxylases; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating; D019438:Ritonavir