Population Pharmacokinetics of Isoniazid, Pyrazinamide, and Ethambutol in Pregnant South African Women with Tuberculosis and HIV.
NAT2
NONMEM
modeling
pharmacometrics
pregnancy
simulation
Journal
Antimicrobial agents and chemotherapy
ISSN: 1098-6596
Titre abrégé: Antimicrob Agents Chemother
Pays: United States
ID NLM: 0315061
Informations de publication
Date de publication:
21 02 2020
21 02 2020
Historique:
received:
01
10
2019
accepted:
05
12
2019
pubmed:
18
12
2019
medline:
22
12
2020
entrez:
18
12
2019
Statut:
epublish
Résumé
Tuberculosis is an important cause of maternal morbidity, but little is known about the effects of pregnancy on antituberculosis drug concentrations. We developed population pharmacokinetic models to describe drug dispositions of isoniazid, pyrazinamide, and ethambutol in pregnant women with tuberculosis and HIV. HIV-positive pregnant women with tuberculosis receiving standard first-line tuberculosis treatment and participating in Tshepiso, a prospective cohort study in Soweto, South Africa, underwent sparse pharmacokinetic sampling at >36 weeks of gestation and 7 weeks postpartum. The effects of pregnancy on the pharmacokinetics of isoniazid, pyrazinamide, and ethambutol were investigated via population pharmacokinetic modeling. Isoniazid, pyrazinamide, and ethambutol concentrations were available for 29, 18, and 18 women, respectively. Their median weight was 66 kg while pregnant and 64 kg postpartum. No significant differences were observed in drug clearance, volume of distribution, or bioavailability during and after pregnancy. The model-estimated isoniazid, pyrazinamide, and ethambutol area under the concentration-time curve from 0 to 24 h (AUC
Identifiants
pubmed: 31844002
pii: AAC.01978-19
doi: 10.1128/AAC.01978-19
pmc: PMC7038290
pii:
doi:
Substances chimiques
Antitubercular Agents
0
Pyrazinamide
2KNI5N06TI
Ethambutol
8G167061QZ
Isoniazid
V83O1VOZ8L
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : P30 AI094189
Pays : United States
Organisme : FDA HHS
ID : R01 FD004794
Pays : United States
Organisme : NIAID NIH HHS
ID : K23 AI080842
Pays : United States
Organisme : Wellcome Trust
ID : 206379/Z/17/Z
Pays : United Kingdom
Organisme : NICHD NIH HHS
ID : R01 HD064354
Pays : United States
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : FIC NIH HHS
ID : D43 TW010340
Pays : United States
Organisme : NIAID NIH HHS
ID : K24 AI150349
Pays : United States
Organisme : NIAID NIH HHS
ID : K23 AI129854
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI106701
Pays : United States
Informations de copyright
Copyright © 2020 American Society for Microbiology.
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