Pharmacokinetics of reduced-dose indinavir/ritonavir 400/100 mg twice daily in HIV-1-infected Thai patients.
OBJECTIVE
To study the pharmacokinetics of indinavir/ ritonavir 400/100 mg twice daily in antiretroviral-naive patients at Srinagarind Hospital in Khon Kaen, Thailand.


METHODS
This was a steady-state, open-label pharmacokinetic study of 19 patients. A 12 h pharmacokinetic curve was recorded after an overnight fast. Plasma levels of indinavir and ritonavir were determined by a validated HPLC method. Virological failure was defined according to the most recent US Department of Health and Human Services guidelines as a viral load above 400 copies/ml at week 24.


RESULTS
Median baseline values for CD4 and viral load were 13cells/mm3 and 167000 copies/ml, respectively. The median (interquartile ranges) for indinavir AUC, Cmax and Cmin were 18.1 (15.3-23.8) mg/l x h, 4.1 (3.6-4.8) mg/l and 0.17 (0.12-0.30) mg/l, respectively. These values represent 37%, 39% and 24% of the AUC, Cmax and Cmin values found, respectively, for the indinavir/ritonavir 800/100 mg dose in HIV-1-infected Thai patients. Short-term virological response was satisfactory. There were three subjects with an indinavir Cmin. below the target value of 0.10 mg/l, of whom one had virological failure (33%). Among the other 16 subjects with an indinavir Cmin above 0.10 mg/l, there was also one virological failure (6%) (P=0.30).


CONCLUSIONS
Indinavir exposure in this reduced-dose regimen of 400 mg with 100 mg ritonavir twice daily was more than dose-proportionally lower than previously observed with the indinavir/ritonavir 800/100 mg twice daily regimen. Therapeutic Cmin levels of indinavir were achieved in >80% of the subjects and short-term virological response was satisfactory in this cohort of patients starting highly active antiretroviral therapy at an advanced disease stage with high baseline viral loads.
Boyd
Mark
M
HIV Netherlands Australia Thailand Research Collaboration, Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
Mootsikapun
Piroon
P
Burger
David
D
Chuenyam
Theshinee
T
Ubolyam
Sasiwimol
S
Mahanontharit
Apicha
A
Sangkote
Jongkol
J
Bunyaprawit
Parichart
P
Horsakulchai
Manasinee
M
Lange
Joep
J
Cooper
David
D
Phanuphak
Praphan
P
Ruxrungtham
Kiat
K
D000284:Administration, Oral; D000328:Adult; D015331:Cohort Studies; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D015497:HIV-1; D006761:Hospitals; D006801:Humans; D019469:Indinavir / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D019438:Ritonavir / Q000493:pharmacokinetics*; D018119:Stavudine / Q000627:therapeutic use; D013785:Thailand
D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D019469:Indinavir; D018119:Stavudine; D019438:Ritonavir