Pharmacokinetics of Oral Pyrazinamide in Normal Subjects

Park, C. W.; Shin, S. G.; Lee, S. H.; Han, Y. C.; Lee, J. S.; Kim, S. G.; Kim, D. J.

doi:1986.33.2.88

Tuberc Respir Dis > Volume 33(2); 1986 > Article

Original Article

Tuberculosis and Respiratory Diseases 1986;33(2):88-94.
DOI: https://doi.org/10.4046/trd.1986.33.2.88 Published online June 1, 1986.

Pharmacokinetics of Oral Pyrazinamide in Normal Subjects

C. W. Park¹, S. G. Shin¹, S. H. Lee¹, Y. C. Han², J. S. Lee², S. G. Kim², D. J. Kim²

¹Department of Pharmacology, College of Medicine, Seoul National University
²Department of Internal Medicine, College of Medicine, Seoul National University

정상인에서의 경구용 Pyrazinamide의 약력학적 연구

박찬웅¹, 신상구¹, 이선희¹, 한용철², 이정상², 김성권², 김대중²

Abstract

The pharmacokinetics of single oral dose(l gm) of pyrazinamide was studied in 13-normal subjects. Three of them received the dose as the commercial tablet and again as the solution preparation with at least 7 days interval. Serum and urine samples were collected at frequent intervals for up to 12 and 24hr, respectively. Peak serum concentrations ranged from 22.05 to 39.92 μg/ml. The mean serum half-life of pyrazinamide was 8. 21±1. 38 hr. Unchanged drug excreted in urine up to 24 hr averaged 28.3 ± 5.9% of the dose administered. The rnean value for the volurne of distribution(Vl_daea/F) and total clearance(Cl_t/F) using a non-method was 0.52 ± 0.09 L/kg and 46.02 ± 9.46 rnl/hr/kg, respectively. Renal clearance ranged from 10.49 to 26.68 ml/hr/ kg, indicating dominant tubular reabsorption. Excretion ratio of pyrazinamide in two subjects with relatively constant urine flow during experiment was gradually increased parallel to the reduction of serum concentration, meaning existence of active tubular secretion. The mean in vivo dissolution time of pyrazinamide tablet was 0.62 ± 0.88 hr and its relative bioavailability to a aqueous solution was 1.03 ± 0.07.