Isoniazid Levels in the Bronchoalveolar Lavage Fluid of Patients with Pulmonary Tuberculosis

Abstract

Isoniazid (INH) is one of the most important first line drugs in the treatment of tuberculosis. We utilized high performance liquid chromatography with a hydrazone extraction technique to measure INH in bronchoalveolar lavage (BAL) fluid specimens from six patients with active pulmonary tuberculosis. We found BAL fluid INH levels to be similar to 2-h peak serum levels. The concentration of INH in BAL fluid from lobes with infiltrate was similar to the concentration of INH in BAL fluid from lobes without infiltrate (0.062 microgram/ml and 0.073 microgram/ml, respectively). After adjusting for protein concentration in the BAL fluid, INH levels in lobes with infiltrate were threefold lower than in lobes without infiltrate. The correlation between the concentration of INH in serum and BAL fluid approached significance after correcting for protein (lobes with infiltrate, r2 = 0.60 (p = 0.07); lobes without infiltrate, r2 = 0.50 (p = 0.12). INH penetrates into bronchoalveolar fluid, and concentrations of INH in the BAL fluid suggest that assessment of the INH serum concentration is adequate to evaluate bioavailability of the drug in patients with pulmonary tuberculosis.

Pharmacokinetic Evaluation of the Penetration of Antituberculosis Agents in Rabbit Pulmonary Lesions

“…Overall, the estimated PC lesion values for RIF and MXF followed the same trend as the PCs reported for ELF in clinical studies (51,62), while the reported penetration of INH and PZA in ELF (10,11,43) is quite different from the corresponding PC lesion obtained in this study.…”

Population Modeling and Simulation Study of the Pharmacokinetics and Antituberculosis Pharmacodynamics of Isoniazid in Lungs

“…It is also acknowledged that study data were sparse, especially drug concentrations measured in lungs, as only a single sample obtained 2 h or 4 h after the dose was available for each subject (17,18). Our model-based estimates of drug AUC and PK profiles in lungs are based on this limited information; therefore, delayed diffusion and accumulation of INH in the ELF cannot be ruled out.…”

“…This was a retrospective analysis of primary pharmacokinetic data from three original studies published by Conte et al, O'Brien et al, and Katiyar et al (17)(18)(19). Details about subjects' characteristics, informed consent, and study design are fully available in those publications (17)(18)(19). Briefly, the study by Conte et al (17) included 80 adult volunteers without TB, i.e., 20 men with AIDS, 20 men without AIDS, 20 women with AIDS, and 20 women without AIDS.…”

“…For the determination of INH concentrations in ELF and AC, the volume of ELF recovered by BAL was calculated by using the urea dilution method (22), while the volume of AC was estimated from the cell count performed on the BAL fluid. The study by O'Brien et al (18) included 6 patients with active pulmonary TB, i.e., 1 woman with AIDS, 2 men without AIDS, and 3 men with unknown AIDS status. These subjects received 300 mg of INH, administered orally, once a day as part of a four-drug therapeutic regimen, for a minimum of 5 days.…”

Mutant Prevention Concentration of Isoniazid, Rifampicin and Rifabutin against <i>Mycobacterium tuberculosis</i>

“…Depending on the individual patient, the isoniazid concentration varies greatly in serum (0.3-7.1 g/ml 1 h after the dose) [13] and in bronchoalveolar lavage fl uid from lobes with 0.062 mg/l infi ltrate [14] . These levels are modifi ed by the type of food consumed.…”