Therapeutic drug monitoring of rifampicin, isoniazid, and pyrazinamide in newly-diagnosed pulmonary tuberculosis outpatients in Denpasar area

Abstract

Background: Therapeutic drug monitoring (TDM) has the potency to enhance the therapeutic outcome of rifampicin, isoniazid, and pyrazinamide, the backbone of first-line anti-tuberculosis (TB) therapy. The implementation of TDM is understudied for newly-diagnosed lung TB outpatients in the Denpasar area. Aim: To determine the prevalence of low plasma concentration of three first-line anti-TB drugs (rifampicin, isoniazid, and pyrazinamide). Methods: Subjects were newly-diagnosed lung TB adult outpatients from the Denpasar area, aged >18 years old, without comorbidity (HIV or diabetes), not pregnant and not using comedications for at least two days before the test. The subjects received daily anti-TB drugs for at least ten days before the test. SGOT, SGPT, and albumin levels were tested at the time before administration of RHZE 4-FDC tablet. Subjects were tested for plasma concentration at 2 and 6 hours after ingestion of RHZE 4-FDC tablet. Plasma levels of rifampicin, isoniazid, and pyrazinamide were analyzed using HPTLC spectrophotodensitometry method. Results: 28 of 32 subjects had low plasma concentrations of rifampicin, 9 of 24 subjects had low plasma concentrations of isoniazid, 4 of 24 subjects had high plasma concentrations of isoniazid, and 14 of 31 subjects had low levels of pyrazinamide; 3 subjects had plasma concentration of three drugs within the expected range simultaneously. Conclusion: Almost all subjects had low plasma concentration of rifampicin, isoniazid, and pyrazinamide. Only a limited number of subjects had plasma concentration within the target range of the three drugs simultaneously.