AEGiS-13IAC: Steady-state plasma pharmacokinetics of amprenavir (APV) 450 mg bid and ritonavir (RTV) 200 mg bid with or without Efavirenz (EFV) in HIV-1 infected Individuals.

13th International AIDS Conference

Durban, South Africa - July 9-July 14, 2000

Steady-state plasma pharmacokinetics of amprenavir (APV) 450 mg bid and ritonavir (RTV) 200 mg bid with or without Efavirenz (EFV) in HIV-1 infected Individuals.

Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. WeOrB547)

Degen O, Kurowski M, van Lunzen J, Stellbrink H-J
O. Degen, University Hospital Eppendorf, Medical Department, Pav. 33, INFE, Martinistr. 52, 20246 Hamburg, Germany, Tel.: +49-40-42803-2118, Fax: +49-40-42803-5187, E-mail: hj.stellbrink.hivweb@t-online.de

BACKGROUND: To investigate APV levels in a low-dose rescue therapy combination with RTV and the impact of EFV on APV levels in this double-PI combination.

METHODS: Steady-state plasma-levels of APV and RTV were analyzed in 8 HIV-infected patients receiving a combination of both drugs with or without 600 mg EFV qd. 7 male and 1 female subjects were treated with APV 450 mg bid and RTV 200 mg bid plus min 2 NRTI for at least 4 weeks. 4/8 pts. received additional EFV in standard doses. Cmin, Cmax, AUC 0-8, t é and t max were calculated. Result: Cmin and Cmax of APV were high and stable in all patients with or without coadministration of EFV. All patients: 8, with EFV: 4, without EFV:4 The Cmin(ng/ml)was 1996 (Range 1101-5553) for all pts., 2720 (Range 1943-5553) in the EFV group and 1511 (Range 1101-2049) in pts. without EFV. The Cmax (ng/ml) was 7739 (Range 4950-15041) for all pts., 9999 (Range 5534-10900) in the EFV group and 6077 (Range 4950-11983) in pts. without EFV. The AUC 0-8 (ng/ml) levels were 29365 (Range 21129-60468) for all pts., 35012 (Range 25984-60468) for EFV pts., and 27359 (Range 21229-56455) in pts. without EFV. The elimination half live time (t é /h) was 2.49 h (Range 1.98-3.42) in all pts., 2.2 h (Range 1.98-2.77) in the EFV group, and 2.9 h (Range 2.2-3.42) in pts. without EFV. The t max (h) was 1.5 h (Range 1-4) in all pts., 1 h (Range 1-1) in EFV pts., and 2 (Range 2-4) in pts. without EFV. All values were calculated as medians. The combination was well tolerated (Grade I diarrhea in 2 pts., feeling of discomfort in 1 pts.). No patient discontinued therapy due to adverse events.

CONCLUSIONS: These data confirm the increase in plasma concentrations of APV by RTV using a low dose of APV. EFV had no negative impact on APV plasma-levels in this combination. Treatment was safe and well tolerated. The antiviral potential of low-dose RTV/APV should be investigated in prospective clinical trials.

Keywords: AEGIS, Ritonavir, Oxazines, HIV-1, Sulfonamides, HIV Infections, Area Under Curve, 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic, Acid, efavirenz, VX 478, 4-benzamido-4'-isothiocyanostilbene-2,2'-disulfonate, Female, Male, Human, pharmacokinetics
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WeOrB547