Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Pharmacokinetics of first-line tuberculosis drugs in Tanzanian patients
Antimicrobial Agents and Chemotherapy, Volume 57, No. 7, Year 2013
Notification
URL copied to clipboard!
Description
East Africa has a high tuberculosis (TB) incidence and mortality, yet there are very limited data on exposure to TB drugs in patients from this region. We therefore determined the pharmacokinetic characteristics of first-line TB drugs in Tanzanian patients using intensive pharmacokinetic sampling. In 20 adult TB patients, plasma concentrations were determined just before and at 1, 2, 3, 4, 6, 8, 10, and 24 h after observed drug intake with food to estimate the areas under the curve from 0 to 24 h (AUC0-24) and peak plasma concentrations (Cmax) of isoniazid, rifampin, pyrazinamide, and ethambutol. Acetylator status for isoniazid was assessed phenotypically using the isoniazid elimination half-life and the acetylisoniazid/isoniazid metabolic ratio at 3 h postdose. The geometric mean AUC0-24s were as follows: isoniazid, 11.0 h · mg/liter; rifampin, 39.9 h · mg/liter; pyrazinamide, 344 h · mg/liter; and ethambutol, 20.2 h · mg/liter. The Cmax was below the reference range for isoniazid in 10/19 patients and for rifampin in 7/20 patients. In none of the patients were the Cmaxs for pyrazinamide and ethambutol below the reference range. Elimination half-life and metabolic ratio of isoniazid gave discordant phenotyping results in only 2/19 patients. A substantial proportion of patients had an isoniazid and/or rifampin Cmax below the reference range. Intake of TB drugs with food may partly explain these low drug levels, but such a drug intake reflects common practice. The finding of low TB drug concentrations is concerning because low concentrations have been associated with worse treatment outcome in several other studies. Copyright © 2013, American Society for Microbiology.
Authors & Co-Authors
Tostmann, Alma
Netherlands, Nijmegen
Radboud University Medical Center
Mtabho, Charles M.
Tanzania, Moshi
Kilimanjaro Christian Medical Centre
Semvua, Hadija Hamis
Tanzania, Moshi
Kilimanjaro Christian Medical Centre
van den Boogaard, Jossy
Netherlands, Nijmegen
Radboud University Medical Center
Tanzania, Moshi
Kilimanjaro Christian Medical Centre
Kibiki, Gibson S.
Tanzania, Moshi
Kilimanjaro Christian Medical Centre
Boeree, Martin Johan
Netherlands, Nijmegen
Radboud University Medical Center
Aarnoutse, Rob Edward
Netherlands, Nijmegen
Radboud University Medical Center
Statistics
Citations: 62
Authors: 7
Affiliations: 2
Identifiers
Doi:
10.1128/AAC.02599-12
ISSN:
00664804
e-ISSN:
10986596
Research Areas
Food Security
Infectious Diseases
Noncommunicable Diseases
Study Design
Cohort Study
Study Locations
Multi-countries