A Physiologically Based Pharmacokinetic Model of Isoniazid and Its Application in Individualizing Tuberculosis Chemotherapy.

ABSTRACT: Due to its high early bactericidal activity, isoniazid (INH) plays an essential role in tuberculosis treatment. Genetic polymorphisms of N-acetyltransferase type 2 (NAT2) cause a trimodal distribution of INH pharmacokinetics in slow, intermediate, and fast acetylators. The success of INH-based chemotherapy is associated with acetylator and patient health status. Still, a standard dose recommended by the FDA is administered regardless of acetylator type or immune status, even though adverse effects occur in 5 to 33% of all patients. Slow acetylators have a higher risk of development of drug-induced toxicity, while fast acetylators and immune-deficient patients face lower treatment success rates. To mechanistically assess the trade-off between toxicity and efficacy, we developed a physiologi

SUBMITTER: Cordes H 

PROVIDER: S-EPMC5038291 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature