Pharmacokinetics of efavirenz (EFV) alone and in combination therapy with nelfinavir (NFV) in HIV-1 infected patients.
OBJECTIVE
To define the pharmacokinetic profile of efavirenz (EFV) in HIV-1 infected patients, when administered alone or with nelfinavir (NFV).


METHODS
Eleven HIV-positive patients, in steady-state treatment with EFV and 11 patients in steady-state treatment with EFV+NFV, were evaluated. Blood samples for pharmacokinetic analysis were obtained during a dosage interval. Plasma concentrations of EFV were determined by h.p.l.c.


RESULTS
No significant difference was found between the principal pharmacokinetic parameters of EFV when administered alone or in combination with NFV (mean AUC: 57.1-7727.3 vs 60.9+/-12.3 microg ml-1 h; mean CL/F: 0.18+/-0.072 vs 0.16+/-0.04 l h-1 kg-1; mean Cmax: 4.0+/-1.7 vs 4.3+/-1.2 microg ml-1, and mean tmax: 4.1+/-1.7 vs 3.5+/-0.5 h) Mean trough plasma concentrations (C0) of EFV were 1.64+/-0.93 microg ml-1, with and without NFV. A good correlation was found between C0 and AUC(0,24h) (r=0.96; P<0. 01).


CONCLUSIONS
Despite the common metabolic pathway, there was no significant influence of NFV on the pharmacokinetics of EFV. EFV exhibits a relatively low interindividual variability and a dosing regimen of 600 mg day-1 assures plasma concentrations that are adequate for inhibition of viral replication.
Villani
P
P
Department of Pharmacology, IRCCS Policlinico S. Matteo. Pavia, Italy.
Regazzi
M B
MB
Castelli
F
F
Viale
P
P
Torti
C
C
Seminari
E
E
Maserati
R
R
D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D048588:Benzoxazines; D002851:Chromatography, High Pressure Liquid; D003521:Cyclopropanes; D005260:Female; D015658:HIV Infections / Q000378:metabolism*; D015497:HIV-1; D006801:Humans; D008297:Male; D019888:Nelfinavir / Q000493:pharmacokinetics*; D010078:Oxazines / Q000493:pharmacokinetics*; D013056:Spectrophotometry, Ultraviolet
D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D010078:Oxazines; D019888:Nelfinavir; C098320:efavirenz