We have located open access text paper links.
Pharmacokinetics and pharmacodynamics of high-dose isoniazid for the treatment of rifampicin- or multidrug-resistant tuberculosis in Indonesia.
Journal of Antimicrobial Chemotherapy 2024 March 10
BACKGROUND: Pharmacokinetic data on high-dose isoniazid for the treatment of rifampicin-/multidrug-resistant tuberculosis (RR/MDR-TB) are limited. We aimed to describe the pharmacokinetics of high-dose isoniazid, estimate exposure target attainment, identify predictors of exposures, and explore exposure-response relationships in RR/MDR-TB patients.
METHODS: We performed an observational pharmacokinetic study, with exploratory pharmacokinetic/pharmacodynamic analyses, in Indonesian adults aged 18-65 years treated for pulmonary RR/MDR-TB with standardized regimens containing high-dose isoniazid (10-15 mg/kg/day) for 9-11 months. Intensive pharmacokinetic sampling was performed after ≥2 weeks of treatment. Total plasma drug exposure (AUC0-24) and peak concentration (Cmax) were assessed using non-compartmental analyses. AUC0-24/MIC ratio of 85 and Cmax/MIC ratio of 17.5 were used as exposure targets. Multivariable linear and logistic regression analyses were used to identify predictors of drug exposures and responses, respectively.
RESULTS: We consecutively enrolled 40 patients (median age 37.5 years). The geometric mean isoniazid AUC0-24 and Cmax were 35.4 h·mg/L and 8.5 mg/L, respectively. Lower AUC0-24 and Cmax values were associated (P < 0.05) with non-slow acetylator phenotype, and lower Cmax values were associated with male sex. Of the 26 patients with MIC data, less than 25% achieved the proposed targets for isoniazid AUC0-24/MIC (n = 6/26) and Cmax/MIC (n = 5/26). Lower isoniazid AUC0-24 values were associated with delayed sputum culture conversion (>2 months of treatment) [adjusted OR 0.18 (95% CI 0.04-0.89)].
CONCLUSIONS: Isoniazid exposures below targets were observed in most patients, and certain risk groups for low isoniazid exposures may require dose adjustment. The effect of low isoniazid exposures on delayed culture conversion deserves attention.
METHODS: We performed an observational pharmacokinetic study, with exploratory pharmacokinetic/pharmacodynamic analyses, in Indonesian adults aged 18-65 years treated for pulmonary RR/MDR-TB with standardized regimens containing high-dose isoniazid (10-15 mg/kg/day) for 9-11 months. Intensive pharmacokinetic sampling was performed after ≥2 weeks of treatment. Total plasma drug exposure (AUC0-24) and peak concentration (Cmax) were assessed using non-compartmental analyses. AUC0-24/MIC ratio of 85 and Cmax/MIC ratio of 17.5 were used as exposure targets. Multivariable linear and logistic regression analyses were used to identify predictors of drug exposures and responses, respectively.
RESULTS: We consecutively enrolled 40 patients (median age 37.5 years). The geometric mean isoniazid AUC0-24 and Cmax were 35.4 h·mg/L and 8.5 mg/L, respectively. Lower AUC0-24 and Cmax values were associated (P < 0.05) with non-slow acetylator phenotype, and lower Cmax values were associated with male sex. Of the 26 patients with MIC data, less than 25% achieved the proposed targets for isoniazid AUC0-24/MIC (n = 6/26) and Cmax/MIC (n = 5/26). Lower isoniazid AUC0-24 values were associated with delayed sputum culture conversion (>2 months of treatment) [adjusted OR 0.18 (95% CI 0.04-0.89)].
CONCLUSIONS: Isoniazid exposures below targets were observed in most patients, and certain risk groups for low isoniazid exposures may require dose adjustment. The effect of low isoniazid exposures on delayed culture conversion deserves attention.
Full text links
Related Resources
Trending Papers
A Guide to the Use of Vasopressors and Inotropes for Patients in Shock.Journal of Intensive Care Medicine 2024 April 14
Prevention and treatment of ischaemic and haemorrhagic stroke in people with diabetes mellitus: a focus on glucose control and comorbidities.Diabetologia 2024 April 17
British Society for Rheumatology guideline on management of adult and juvenile onset Sjögren disease.Rheumatology 2024 April 17
Diagnosis and Management of Cardiac Sarcoidosis: A Scientific Statement From the American Heart Association.Circulation 2024 April 19
Albumin: a comprehensive review and practical guideline for clinical use.European Journal of Clinical Pharmacology 2024 April 13
Eosinophilic Esophagitis: Clinical Pearls for Primary Care Providers and Gastroenterologists.Mayo Clinic Proceedings 2024 April
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app