Phamacokinetics of 14C-teicoplanin in healthy volunteers

Buniva, G.; Favero, A. Del; Bernareggi, A.; Patoia, L.; Palumbo, Renato

doi:10.1093/jac/21.suppl_a.23

Cited by 36 publications

(18 citation statements)

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“…injection of 3 mg/kg, a mean peak serum level of 7.12 μg/ mL was reached in 2 h and thereafter serum levels followed those attained after an identical i.v. dose, being greater than 2 μg/mL at 24 h. The elimination half-life of the drug was about 47 h. Similar results were obtained by Buniva et al ( 1988 ), who gave 400 mg of teicoplanin i.v. over 60 s to volunteers.…”

Section: Pk Of Teicoplaninsupporting

confidence: 83%

Glycopeptides

Gyssens

2013

Fundamentals of Antimicrobial Pharmacokinetics and Pharmacodynamics

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Glycopeptides are a class of antibiotic drugs that is composed of glycosylated cyclic or polycyclic nonribosomal peptides. Older molecules used in clinical practice are vancomycin and teicoplanin. Oritavancin, dalbavancin, and telavancin belong to the subclass of lipoglycopeptides. Glycopeptides inhibit bacterial cell wall peptoglycan synthesis of aerobic and anaerobic Gram-positive bacteria. Glyco (lipo)peptides are not absorbed orally and have to be administered intravenously. In this chapter, the pharmacokinetics (Pk) and the pharmacodynamics (Pd) of the glycopeptides are studied. Pk in serum as well as protein binding and elimination are reviewed. Pharmacodynamic data include MICs of Gram-positive bacteria, PK/Pd effects in in vitro systems, animal models and human studies. Adverse effects of glycopeptides on the host are concentration related nephro-and ototoxicity. In the past, because of fear of toxicity, the older glycopeptides have been underdosed in many settings. The implementation of Pk/Pd knowledge into clinical practice by e.g. administering higher doses of vancomycin and teicoplanin and using continuous infusion of vancomycin is urgently needed. This chapter contains clinical vignettes showing the benefi t of Therapeutic Drug Monitoring of glycopeptides.

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Section: Pk Of Teicoplaninsupporting

confidence: 83%

Glycopeptides

Gyssens

2013

Fundamentals of Antimicrobial Pharmacokinetics and Pharmacodynamics

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“…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.…”

supporting

confidence: 72%

Teicoplanin metabolism in rats

Zerilli¹,

Cavenaghi²,

Bernareggi³

et al. 1989

Antimicrob Agents Chemother

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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...

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“…Results of previous pharmacokinetic studies, including studies with [14C]teicoplanin, indicated that teicoplanin is predominantly renally eliminated (3,4). The finding of a lower CLR than CLT in early studies probably reflects the failure to collect urine for a sufficiently long period of time.…”

Section: Methodsmentioning

confidence: 99%

Teicoplanin pharmacokinetics in healthy volunteers after administration of intravenous loading and maintenance doses

Outman

Nightingale

Sweeney

et al. 1990

Antimicrob Agents Chemother

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Teicoplanin is an investigational glycopeptide antibiotic that is structurally and microbiologically similar to vancomycin. Since teicoplanin possesses a very long elimination half-life, the manufacturer suggests that the drug be administered every 12 h for the first day of therapy and once daily thereafter. We studied the multiple-dose (6 mg/kg per dose) pharmacokinetics of teicoplanin in volunteers following intravenous administration every 12 h for 5 days and then every 24 h for 9 days in an attempt to identify the optimal duration of the every-12-h loading-dose regimen. Multiple serum samples were obtained throughout the study, including intensive sampling after the first and last doses; urine was collected during the entire study. A three-exponential equation was fitted to the serum concentration data. The mean terminal-phase half-life was 157 +/- 93 h. Concentrations of teicoplanin in serum similar to those observed after the administration of the last dose (day 14) were observed following the fourth or fifth dose given every 12 h. Therefore, it is suggested that for clinical dosing regimens for teicoplanin, dosing every 12 h for approximately 48 h should be used, followed by once-daily dosing thereafter.

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Phamacokinetics of 14C-teicoplanin in healthy volunteers

Cited by 36 publications

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Glycopeptides

Glycopeptides

Teicoplanin metabolism in rats

Teicoplanin pharmacokinetics in healthy volunteers after administration of intravenous loading and maintenance doses

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