PHARMACOKINETIC STUDY ON TE-031 (A-56268) IN SUBJECTS WITH VARIOUS DEGREES OF RENAL DYSFUNCTION

• Published in: CHEMOTHERAPY Vol. 37; no. 1; pp. 15 - 21
• Main Authors: SHIGEOKA, HIDENOBU, TAKII, MASAHIDE, IBARAGI, KAZUO, KOHNO, KENJI, KUWAHARA, KENSUKE
• Format: Journal Article
• Language: Japanese
• Published: Japanese Society of Chemotherapy 1989; 公益社団法人 日本化学療法学会
• Subjects: Pharmacokinetics; Renal dysfunction; TE-031
• ISSN: 0009-3165; 1884-5894
• DOI: 10.11250/chemotherapy1953.37.15

We carried out a pharmacokinetic study on TE-031 (A-56268), a newly developed macrolide antibiotic, in 20 volunteers with various degrees of renal dysfunction. TE-031 was given orally at a dose of 200 mg, then blood and urine were collected at selected time intervals. Serum and urine concentrations of the drug were determined by agar-disk method, using M. luteus ATCC 9341 as a test organism, or high-performance liquid chromatography. The pharmacokinetic parameters of TE-031 were calculated from the average serum concentrations obtained by bioassay, according to a one-compartment open model. Cmax, Kel and AUC in normal subjects were 2.02 μg/ml, 0.291h-1 and 8.89μg·h/ml, while they were 3.54 μg/ml, 0.113h-1 and 36.89 μg·h/ml, in patients with severe renal dysfunction (Ccr=5ml/min). Ccr showed significant linear correlations with total body clearance, Kel and AUC, giving a linear regression equation of Kel=0.0991+0.0017 Ccr. This strongly suggests that TE-031 is mainly excreted via kidneys. The cumulative amount of TE-031 excreted in urine over 6 h in normal subjects was 26.5%, of the dose, but this was as little as 3.3% in patients with severe renal dysfunction. The metabolites of TE-031 in serum and urine were not significantly affected by the degree of renal dysfunction. Recommendations for dosing of TE-031 in patients with reduced renal function are given.