Population pharmacokinetics of rifampin in pulmonary tuberculosis patients, including a semimechanistic model to describe variable absorption.

Population pharmacokinetics of rifampin in pulmonary tuberculosis patients, including a semimechanistic model to describe variable absorption. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Population pharmacokinetics of rifampin in pulmonary tuberculosis patients, including a semimechanistic model to describe variable absorption. Abstract Text:

This article describes the population pharmacokinetics of rifampin in South African pulmonary tuberculosis patients. Three datasets containing 2,913 rifampin plasma concentration-time data points, collected from 261 South African pulmonary tuberculosis patients aged 18 to 72 years and weighing 28.5 to 85.5 kg and receiving regular daily treatment that included administration of rifampin (450 to 600 mg) for at least 10 days, were pooled. A compartmental pharmacokinetic model was developed using nonlinear mixed-effects modeling. Variability in the shape of the absorption curve was described using a flexible transit compartment model, in which a delay in the onset of absorption and a gradually changing absorption rate were modeled as the passage of drug through a chain of hypothetical compartments, ultimately reaching the absorption compartment. A previously described implementation was extended to allow its application to multiple-dosing data. The typical population estimate of oral clearance was 19.2 liters.h(-1), while the volume of distribution was estimated to be 53.2 liters. Interindividual variability was estimated to be 52.8% for clearance and 43.4% for volume of distribution. Interoccasional variability was estimated for CL/F (22.5%) and mean transit time during absorption (67.9%). The use of single-drug formulations was found to increase both the mean transit time (by 104%) and clearance (by 23.6%) relative to fixed-dose-combination use. A strong correlation between clearance and volume of distribution suggested substantial variability in bioavailability, which could have clinical implications, given the dependence of treatment effectiveness on exposure. The final model successfully described rifampin pharmacokinetics in the population studied and is suitable for simulation in this context.

Population pharmacokinetics of rifampin in pulmonary tuberculosis patients, including a semimechanistic model to describe variable absorption. Publishing Authors By Initials

For similar abstracts research abstracts see: abstracts research

PUBMED ID PMID:

MEDLINE DATE:

Population pharmacokinetics of rifampin in pulmonary tuberculosis patients, including a semimechanistic model to describe variable absorption. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Antimicrobial agents and chemotherapy

VOLUME: 52

Page Numbers: 2138-48

Journal Abbreviation: Antimicrob. Agents Chemother.

ISSN: 1098-6596

DAY: 7

MONTH: 04

YEAR: 2008

Population pharmacokinetics of rifampin in pulmonary tuberculosis patients, including a semimechanistic model to describe variable absorption. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 315061

Population pharmacokinetics of rifampin in pulmonary tuberculosis patients, including a semimechanistic model to describe variable absorption. Keywords Mesh Terms:

KEYWORDS:

MESH TERMS:

Chemical & Substance for Abstract: Population pharmacokinetics of rifampin in pulmonary tuberculosis patients, including a semimechanistic model to describe variable absorption. Information

Substance Name:

Registry Number:

Grant and Affiliation Information for Population pharmacokinetics of rifampin in pulmonary tuberculosis patients, including a semimechanistic model to describe variable absorption.

AFFILIATION: Division of Clinical Pharmacology, K45 Old Main Building, Groote Schuur Hospital, Observatory 7925, South Africa. Helen.McIlleron@uct.ac.za.

Country: United States

AGENCY:

GRANT:

ACRONYM:

MEDLINETA: Antimicrob Agents Chemother

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Population pharmacokinetics of rifampin in pulmonary tuberculosis patients, including a semimechanistic model to describe variable absorption Related Publications

• A model based assessment of the CYP2B6 and CYP2C19 inductive properties by artemisinin antimalarials: implications for combination regimens.
• Acute effects of ipratropium bromide (ITBR, Sch 1000, Atrovent): a review of previous studies.
• Airway hyperreactivity. Definition and short review.
• Anatomical and pathophysiological considerations in aerosol therapy.
• Anticholinergic drugs--a review.
• Bronchial hyperreactivity.
• Bronchial reactivity in occupational asthma and bronchitis.
• Bronchial reactivity in relation to occupational bronchitis and asthma.
• Chronic cough and expectoration in patients with asthma and in patients with alpha1-antitrypsin deficiency.
• Clinical implications of bronchial hyperreactivity.
• Continuous and intermittent exposure to ethanol: effect on NG 108-15 cell membrane phospholipids.
• Evaluation of ethanol effects on PLC signal transduction pathways using cell lines of neuronal origin.
• Identification and characterization of an essential telomeric repeat binding factor in fission yeast.
• Method evaluation of Fusarium DNA extraction from mycelia and wheat for down-stream real-time PCR quantification and correlation to mycotoxin levels.
• Non-specific bronchial hyperreactivity: correlation to asthma and modifying factors.
• Optimal adaptive design in clinical drug development: a simulation example.
• Population pharmacokinetics of rifampin in pulmonary tuberculosis patients, including a semimechanistic model to describe variable absorption.
• Pulmonary gas exchange at rest and during exercise in chronic bronchitis.
• Total nucleated cell differential for blood and bone marrow using a single tube in a five-color flow cytometer.
• Treatment of respiratory failure.