Ketoconazole is inferior to ritonavir as an alternative booster for saquinavir in a once daily regimen in Thai HIV-1 infected patients.
OBJECTIVE
To improve the pharmacokinetics of protease inhibitors, boosting with low-dose ritonavir is performed. However, toxicity, storage conditions and high costs of antiretroviral treatment may necessitate interruption of ritonavir. Ketoconazole was investigated as a potential booster of once-daily (o.d.) saquinavir.


METHODS
In a single-group, two-period design, 25 virologically and immunologically stable patients on saquinavir/ritonavir 2000/100 mg o.d. were switched to saquinavir/ketoconazole 2000/400 mg o.d. for 2 weeks. Two steady-state pharmacokinetic curves were recorded at both periods.


RESULTS
Fourteen females and 11 male patients were included. Median age was 34 years [interquartile range (IQR), 32-42 years], body weight 54 kg (IQR, 47-59 kg) and body mass index 21 kg/m (19-23 kg/m). The mean saquinavir area under the curve (AUC) during boosting with ritonavir was 57.93 +/- 27.96 mg/h/l, maximum observed concentration (Cmax) was 7.50 +/- 3.45 mg/l and concentration at 24 h (Cmin) was 0.35 +/- 0.30 mg/l. When ketoconazole was used, the saquinavir AUC, Cmax, and Cmin were 12.00 +/- 6.97 mg/h/l, 2.43 +/- 1.35 mg/l and 0.03 +/- 0.04 mg/l, respectively.


CONCLUSIONS
Boosting with ketoconazole resulted in 80% lower exposure to saquinavir. Although saquinavir AUC might still be adequate for treatment, concentrations at 24 h reached levels below the recommended trough concentrations of 0.1 mg/l, which may result in selection of resistant HIV-1 viral strains. Therefore, boosting of saquinavir by ketoconazole is not recommended.
Autar
Reshma Saskia
RS
HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Thai Red Cross Aids Research Centre (TRCARC), 104 Rajdumri Road, 10330 Pathumwan, Bangkok, Thailand. saskia@hivnat.com
Wit
Ferdinand W N M
FW
Sankote
Jongkol
J
Sutthichom
Duanghathai
D
Kimenai
Elly
E
Hassink
Elly
E
Hill
Andrew
A
Cooper
David A
DA
Phanuphak
Praphan
P
Lange
Joep M A
JM
Burger
David M
DM
Ruxrungtham
Kiat
K
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D007654:Ketoconazole / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D019438:Ritonavir / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D019258:Saquinavir / Q000097:blood / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load
D017320:HIV Protease Inhibitors; D019258:Saquinavir; D019438:Ritonavir; D007654:Ketoconazole