AEGiS-15IAC: Pharmacokinetics of standard and lower dose indinavir administered with ritonavir 100mg in Asian HIV-infected patients.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

Pharmacokinetics of standard and lower dose indinavir administered with ritonavir 100mg in Asian HIV-infected patients.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. B10273)

Lee LS, Panchalingam A, Yap MC, Paton NI
Tan Tock Seng Hospital, Singapore, Singapore

BACKGROUND: When co-administered with ritonavir 100mg, lower doses of indinavir than the conventional 800mg may provide equally effective but less toxic drug levels in Asian HIV-infected patients.

METHODS: Pharmacokinetic parameters were measured in patients who reduced indinavir dose from 800mg to 600mg and 400mg for one week each. Subjects: Clinically stable outpatients attending the national HIV referral centre in Singapore who had undetectable viral loads on an indinavir-containing regimen. Main Outcome: Peak and trough concentrations on 3 doses of indinavir. Percentage of patients below an efficacy threshold of 150ng/ml or above a toxicity threshold of 10,000 ng/ml on the 3 doses.

RESULTS: 6 patients were studied, all males of Chinese ethnicity. 5 were also taking efavirenz. Median indinavir peak concentrations were 8057ng/ml, 5281ng/ml and 3053ng/ml on the 800mg, 600mg and 400mg dose of indinavir respectively(P=0.002). Peak concentrations were higher than 10,000ng/ml in one patient on the 800mg dose, and none on the lower indinavir doses. Evening trough concentrations were 56% lower than morning trough concentrations(P=0.002). Median evening trough concentrations were 474ng/ml, 248ng/ml and 141ng/ml on the 800mg, 600mg and 400mg dose of indinavir respectively(P=0.006). Evening trough concentrations were higher than 150ng/ml in all patients on 800mg indinavir, but one patient on 600mg and four patients on 400mg had concentrations below this threshold.

CONCLUSIONS: A 400mg dose of indinavir may not produce adequate evening trough concentrations and should be avoided in patients taking efavirenz and those who likely to have protease inhibitor resistance. A 600mg dose gives adequate concentrations even in patients taking efavirenz and may therefore be a cheaper, safer and less toxic alternative to the 800mg dose. This finding is important in resource-limited settings where the protease inhibitor contributes to the main cost of the anti-retroviral regimen.

Keywords: AEGIS, Indinavir, Ritonavir, Acquired Immunodeficiency Syndrome, HIV, HIV Seropositivity, HIV Infections, Anti-HIV Agents, HIV-1, Viral Load, Oxazines, Area Under Curve, Protease Inhibitors, HIV-2, Singapore, efavirenz, Humans, Male, pharmacokinetics, administration & dosage, pathogenicity

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B10273