Pharmacokinetics of efavirenz (EFV) alone and in combination therapy with nelfinavir (NFV) in HIV-1 infected patients

P. Villani, M. B. Regazzi, F. Castelli, P. Viale, C. Torti, E. Seminari, R. Maserati

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Abstract

Aims. 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 μg ml-1 h; mean CL/F: 0.18 ± 0.072 vs 0.16 ± 0.04 1 h-1 kg-1; mean C(max): 4.0 ± 1.7 vs 4.3 ± 1.2 μg ml-1, and mean t(max): 4.1 ± 1.7 vs 3.5 ± 0.5 h) Mean trough plasma concentrations (C0) of EFV were 1.64 ± 0.93 μg ml-1, with and without NFV. A good correlation was found between C0 and AUC(0,24 h) (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.

Original languageEnglish
Pages (from-to)712-715
Number of pages4
JournalBritish Journal of Clinical Pharmacology
Volume48
Issue number5
DOIs
Publication statusPublished - 1999

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efavirenz
Nelfinavir
HIV-1
Pharmacokinetics
Therapeutics
Area Under Curve
Metabolic Networks and Pathways

Keywords

  • Efavirenz
  • HIV-1 infection
  • Nelfinavir
  • Pharmacokinetic interaction

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

@article{946e1588afa74b9795c2b3ad5c7034bf,
title = "Pharmacokinetics of efavirenz (EFV) alone and in combination therapy with nelfinavir (NFV) in HIV-1 infected patients",
abstract = "Aims. 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 μg ml-1 h; mean CL/F: 0.18 ± 0.072 vs 0.16 ± 0.04 1 h-1 kg-1; mean C(max): 4.0 ± 1.7 vs 4.3 ± 1.2 μg ml-1, and mean t(max): 4.1 ± 1.7 vs 3.5 ± 0.5 h) Mean trough plasma concentrations (C0) of EFV were 1.64 ± 0.93 μg ml-1, with and without NFV. A good correlation was found between C0 and AUC(0,24 h) (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.",
keywords = "Efavirenz, HIV-1 infection, Nelfinavir, Pharmacokinetic interaction",
author = "P. Villani and Regazzi, {M. B.} and F. Castelli and P. Viale and C. Torti and E. Seminari and R. Maserati",
year = "1999",
doi = "10.1046/j.1365-2125.1999.00071.x",
language = "English",
volume = "48",
pages = "712--715",
journal = "British Journal of Clinical Pharmacology",
issn = "0306-5251",
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}

TY - JOUR

T1 - Pharmacokinetics of efavirenz (EFV) alone and in combination therapy with nelfinavir (NFV) in HIV-1 infected patients

AU - Villani, P.

AU - Regazzi, M. B.

AU - Castelli, F.

AU - Viale, P.

AU - Torti, C.

AU - Seminari, E.

AU - Maserati, R.

PY - 1999

Y1 - 1999

N2 - Aims. 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 μg ml-1 h; mean CL/F: 0.18 ± 0.072 vs 0.16 ± 0.04 1 h-1 kg-1; mean C(max): 4.0 ± 1.7 vs 4.3 ± 1.2 μg ml-1, and mean t(max): 4.1 ± 1.7 vs 3.5 ± 0.5 h) Mean trough plasma concentrations (C0) of EFV were 1.64 ± 0.93 μg ml-1, with and without NFV. A good correlation was found between C0 and AUC(0,24 h) (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.

AB - Aims. 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 μg ml-1 h; mean CL/F: 0.18 ± 0.072 vs 0.16 ± 0.04 1 h-1 kg-1; mean C(max): 4.0 ± 1.7 vs 4.3 ± 1.2 μg ml-1, and mean t(max): 4.1 ± 1.7 vs 3.5 ± 0.5 h) Mean trough plasma concentrations (C0) of EFV were 1.64 ± 0.93 μg ml-1, with and without NFV. A good correlation was found between C0 and AUC(0,24 h) (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.

KW - Efavirenz

KW - HIV-1 infection

KW - Nelfinavir

KW - Pharmacokinetic interaction

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U2 - 10.1046/j.1365-2125.1999.00071.x

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JO - British Journal of Clinical Pharmacology

JF - British Journal of Clinical Pharmacology

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