Prothionamide Dose Optimization Using Population Pharmacokinetics for Multidrug-Resistant Tuberculosis Patients.
Antimicrob Agents Chemother
; 66(9): e0189321, 2022 09 20.
Article
em En
| MEDLINE
| ID: mdl-35938799
ABSTRACT
Prothionamide, a second-line drug for multidrug-resistant tuberculosis (MDR-TB), has been in use for a few decades. However, its pharmacokinetic (PK) profile remains unclear. This study aimed to develop a population PK model for prothionamide and then apply the model to determine the optimal dosing regimen for MDR-TB patients. Multiple plasma samples were collected from 27 MDR-TB patients who had been treated with prothionamide at 2 different study hospitals. Prothionamide was administered according to the weight-band dose regimen (500 mg/day for weight <50 kg and 750 mg/day for weight >50 kg) recommended by the World Health Organization. The population PK model was developed using nonlinear mixed-effects modeling. The probability of target attainment, based on systemic exposure and MIC, was used as a response target. Fixed-dose regimens (500 or 750 mg/day) were simulated to compare the efficacies of various dosing regimens. PK profiles adequately described the two-compartment model with first-order elimination and the transit absorption compartment model with allometric scaling on clearance. All dosing regimens had effectiveness >90% for MIC values <0.4 µg/mL in 1.0-log kill target. However, a fixed dose of 750 mg/day was the only regimen that achieved the target resistance suppression of ≥90% for MIC values of <0.2 µg/mL. In conclusion, fixed-dose prothionamide (750 mg/day), regardless of weight-band, was appropriate for adult MDR-TB patients with weights of 40 to 67 kg.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Protionamida
/
Tuberculose Resistente a Múltiplos Medicamentos
Limite:
Adult
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Humans
Idioma:
En
Revista:
Antimicrob Agents Chemother
Ano de publicação:
2022
Tipo de documento:
Article