Teicoplanin metabolism in rats

Abstract

This study was done to see whether teicoplanin undergoes metabolic transformation in rats. Sprague-Dawley rats were given 7.6 mg of ['4Cjteicoplanin (904 U/mg, 7.6 ,uCi/mg) per kg intravenously; 73.2 ± 4.0% of the administered radioactivity and 59.1 4.8% of the administered microbiological activity were recovered in the 24-h urine samples. The difterence between these two values was due to adsorption of teicoplanin to the urinary sediment, making some of the antibiotic not available for microbiological determination. In fact, after a sample of urine was filtered through an Acrodisc (0.45-,Im pore size), radiochemical and microbiological data for the filtrate were very similar. Possible metabolites were looked for by high-performance liquid chromatographic analysis of the teicoplanin complex composition in the urine samples, with both UV and radioactivity detection.The quantitation, based on the 14C percentage in each peak, showed that no more than 3 to 5% of the [14Cjteicoplanin underwent metabolic and/or chemical transformation.The glycopeptide antibiotic teicoplanin (8, 14) was recently introduced in parenteral treatment of severe infections caused by gram-positive aerobic and anaerobic bacteria (13). Teicoplanin is a complex of six major components which, on the basis of separation by reversed-phase highpressure liquid chromatography (HPLC), are classified into two groups, T-A2 (five compounds) and T-A3 (one compound). T-A3 has been shown to be a hydrolysis product of group T-A2 (i). Minor quantities of related substances are also present (4, 7).The in vitro activity against gram-positive clinical isolates of staphylococci and streptococci, the in vivo activity in mice with septicemic infections (50% effective dose given subeutaneously); and the acute toxicity in mice (50% lethal dose given intraperitoneally) of the individual components of the T-A2 group are similar (5). The T-A3 component shows an in vitro activity comparable to those of the individual components of the T-A2 group against some microorganisms, but it is less active against other bacterial species (11).The disposition of teicoplanin was studied in SpragueDawley rats giveh the 14C-labeled teicoplanin complex intravenodsly (3). The plasma concentration profiles of both total radioactivity and microbiological activity fitted a threeexponential equation, but levels of radioactivity were constantly higher than those determined microbiologically. The mean retoveries of teicoplanin in urine were 76.3% as determihed by radioactivity and 47.1% as determined by microbiology. These data are in keeping with the findings in humans (6,16). In this study we aimed at understanding the reasons for this difference and detecting possible metabolic derivatives of teicoplanin. MATERIALS AND METHODSChemicals.[14C]teicoplanin complex 1 was prepared by mixing the two fractions, T-A2-1/2/3 and T-A2-4/5, of the batch Midland 9/84 API, kindly supplied by C. Snipes (Dow Chemical Co., Midland, Mich.), who obtained it by fermentation with 14C-labeled p-hydroxyphenyl-glyc...

Teicoplanin metabolism in humans

“…A study in rats with i.v. administration of teicoplanin showed little metabolic transformation of the antibiotic; in urine collected over 0 to 24 h after drug administration, no more than 3 to 5% of the dose eliminated was found to be metabolized (17). In humans, following i.v.…”