Abstract
Rifampicin (RIF) decreases serum concentrations of several antiretroviral drugs. We carried out a prospective, comparative study to define efavirenz (EFV) pharmacokinetics in 16 cases and 13 controls. Cases were HIV and tuberculosis (TB) co-infected adults assuming RIF 600 mg once daily and EFV 800 mg once daily. Patients on EFV at standard 600 mg dose without RIF were taken as controls. EFV levels in plasma were assayed by high-performance liquid chromatography (HLPC) predose (Ctrough) and at 1, 2, 3, 4, 5, 6, 8, 10, 11, 12, 13, 14, 16, 18, 22 and 24 hours post-dose, and pharmacokinetic parameters were determined by non-compartmental methods. Among cases, 81% were males, mean age was 37 years, 50% were Caucasians, mean weight was 64 kg, mean CD4 cell counts and log HIV RNA copies were 160/μl and 5.2 /μl, respectively. Cases had a significantly higher Cl/F/kg if compared with controls (0.269 ± 0.12 versus 0.167 + 0.05 L/h/kg, p < 0.01). Otherwise, dose-dependent pharmacokinetic parameters of EFV were similar between cases and controls. Interindividual variability was consistently higher among TB cases compared to controls for all considered parameters. All cases completed combined treatment and no increased EFV toxicity was observed. These results suggest that a dose of 800 mg of EFV in association with rifampicin may be appropriate for patients of weight > 60 kg in Europe. Therapeutic drug monitoring may be beneficial for patients on combination therapy with RIF.
Keywords: Efavirenz, rifampicin, pharmacokinetic interaction, HIV infection
Current HIV Research
Title: Multiple-Dose Pharmacokinetics of Efavirenz with and without the Use of Rifampicin in HIV-Positive Patients
Volume: 5 Issue: 3
Author(s): Alberto Matteelli, Mario Regazzi, Paola Villani, Giuseppina De Iaco, Maria Cusato, Anna Cristina C. Carvalho, Silvio Caligaris, Lina Tomasoni, Maria Manfrin, Susanna Capone and Giampiero Carosi
Affiliation:
Keywords: Efavirenz, rifampicin, pharmacokinetic interaction, HIV infection
Abstract: Rifampicin (RIF) decreases serum concentrations of several antiretroviral drugs. We carried out a prospective, comparative study to define efavirenz (EFV) pharmacokinetics in 16 cases and 13 controls. Cases were HIV and tuberculosis (TB) co-infected adults assuming RIF 600 mg once daily and EFV 800 mg once daily. Patients on EFV at standard 600 mg dose without RIF were taken as controls. EFV levels in plasma were assayed by high-performance liquid chromatography (HLPC) predose (Ctrough) and at 1, 2, 3, 4, 5, 6, 8, 10, 11, 12, 13, 14, 16, 18, 22 and 24 hours post-dose, and pharmacokinetic parameters were determined by non-compartmental methods. Among cases, 81% were males, mean age was 37 years, 50% were Caucasians, mean weight was 64 kg, mean CD4 cell counts and log HIV RNA copies were 160/μl and 5.2 /μl, respectively. Cases had a significantly higher Cl/F/kg if compared with controls (0.269 ± 0.12 versus 0.167 + 0.05 L/h/kg, p < 0.01). Otherwise, dose-dependent pharmacokinetic parameters of EFV were similar between cases and controls. Interindividual variability was consistently higher among TB cases compared to controls for all considered parameters. All cases completed combined treatment and no increased EFV toxicity was observed. These results suggest that a dose of 800 mg of EFV in association with rifampicin may be appropriate for patients of weight > 60 kg in Europe. Therapeutic drug monitoring may be beneficial for patients on combination therapy with RIF.
Export Options
About this article
Cite this article as:
Matteelli Alberto, Regazzi Mario, Villani Paola, De Iaco Giuseppina, Cusato Maria, Carvalho C. Anna Cristina, Caligaris Silvio, Tomasoni Lina, Manfrin Maria, Capone Susanna and Carosi Giampiero, Multiple-Dose Pharmacokinetics of Efavirenz with and without the Use of Rifampicin in HIV-Positive Patients, Current HIV Research 2007; 5 (3) . https://dx.doi.org/10.2174/157016207780636588
DOI https://dx.doi.org/10.2174/157016207780636588 |
Print ISSN 1570-162X |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4251 |
Call for Papers in Thematic Issues
Management of HIV: Management of HIV: old challenges and new needs
The aim of this thematic issue is to provide the most recent updates regarding the effective management of HIV infection. Antiretroviral therapy (ART) has significantly decreased HIV-related mortality, leading to an enhancement in the quality of life and life expectancy for people living with HIV (PLWH). Despite the numerous advancements ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Different Methods for Molecular and Rapid Detection of Human Novel Coronavirus
Current Pharmaceutical Design New and Old Hot Drug Targets in Tuberculosis
Current Medicinal Chemistry Virtual Screening Against M. tuberculosis 7,8-Diaminopelargonic Acid Synthase (MtbBioA) and In Silico Toxicity Evaluation of Top Hits
Current Enzyme Inhibition Acetohydroxyacid Synthase: A Target for Antimicrobial Drug Discovery
Current Pharmaceutical Design Electronic-Topological and Neural Network Approaches to the Structure- Antimycobacterial Activity Relationships Study On Hydrazones Derivatives
Medicinal Chemistry Particulate Systems as Adjuvants and Carriers for Peptide and Protein Antigens
Current Drug Delivery Editorial [Hot topic: QSAR and Complex Networks in Pharmaceutical Design, Microbiology, Parasitology, Toxicology, Cancer and Neurosciences (Executive Editor: Humberto Gonzalez-Diaz)]
Current Pharmaceutical Design Gene Therapy Using IL-12 Family Members in Infection, Auto-Immunity, and Cancer
Current Gene Therapy Developing Country Applications of Molecular Farming: Case Studies in South Africa and Argentina
Current Pharmaceutical Design Design, Synthesis and 3-D Characterization of 1-Benzenesulfonyl-1,2,3,4- Tetrahydroquinolines as Lead Scaffold for Antiparasitic Drug
Letters in Drug Design & Discovery Use of Etanercept in the Treatment of Psoriasis and Psoriatic Arthritis
Reviews on Recent Clinical Trials Meet Our Editorial Board Member
Current Medicinal Chemistry Genomic Instability in Cancer: Molecular Mechanisms and Therapeutic Potentials
Current Pharmaceutical Design Enantioselective Organocatalytic Reactions with Isatin
Current Organic Chemistry Exploring Coumarin and Chalcone Analogues as Potential Antimycobacterial Agents
Anti-Infective Agents Structure-Activity Relationship of Supramolecular Compounds in Drug Delivery
Mini-Reviews in Organic Chemistry Glutamate-Based Drugs for the Treatment of Clinical Depression
Central Nervous System Agents in Medicinal Chemistry Understanding Respiratory Syncytial Virus Infection to Improve Treatment and Immunity
Current Molecular Medicine The IL-12 Family of Cytokines in Infection, Inflammation and Autoimmune Disorders
Inflammation & Allergy - Drug Targets (Discontinued) A Review of Recent Advancements in Anti-tubercular Molecular Hybrids
Current Medicinal Chemistry