Population Pharmacokinetics of Isoniazid, Pyrazinamide, and Ethambutol in South African Pregnant Women with Tuberculosis and HIV.

Population Pharmacokinetics of Isoniazid, Pyrazinamide, and Ethambutol in South African Pregnant Women with Tuberculosis and HIV. Antimicrob Agents Chemother. 2019 Dec 16;: Authors: Abdelwahab MT, Leisegang R, Dooley KE, Mathad JS, Wiesner L, McIlleron H, Martinson N, Waja Z, Letutu M, Chaisson RE, Denti P, Tshepiso Study Team Abstract Tuberculosis is an important cause of maternal morbidity, but little is known about the effects of pregnancy on anti-tuberculosis drug concentrations. We developed population pharmacokinetic models to describe drug disposition 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 gestation and 7 weeks postpartum. The effects of pregnancy on the pharmacokinetics of isoniazid, pyrazinamide, and ethambutol were investigated via population pharmacokinetic modelling.Isoniazid, pyrazinamide, and ethambutol concentrations were available for 29, 18, and 18 women respectively. 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 pregnancy and postpartum. The model-estimated isoniazid, pyrazinamide and ethambutol AUC0-24 medians...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research