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Antimicrobial Agents and Chemotherapy, April 2000, p. 916-919, Vol. 44, No. 4
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Pharmacokinetics of an Everninomicin (SCH 27899) in Mice, Rats, Rabbits, and Cynomolgus Monkeys following Intravenous Administration

C. Lin,1,* S. Gupta,1 D. Loebenberg,2 and M. N. Cayen1

Department of Drug Metabolism and Pharmacokinetics1 and Department of Chemotherapy,2 Schering-Plough Research Institute, Kenilworth, New Jersey 07033

Received 7 July 1999/Returned for modification 30 November 1999/Accepted 27 December 1999

The pharmacokinetics of SCH 27899, a novel oligosaccharide compound of the everninomicin class with excellent activity against gram-positive strains, was studied with mice, rats, rabbits, and cynomolgus monkeys following intravenous administration as SCH 27899-N-methylglucamine-hydroxypropyl beta -cyclodextrin. Concentrations of SCH 27899 in mouse serum, rat plasma, and rabbit serum were determined by a high-pressure liquid chromatography method on a poly(styrene-divinyl benzene) column, and those in monkey plasma were determined by a paired-ion chromatographic method. Plasma and serum concentrations of SCH 27899 exhibited a biexponential decline in all species following intravenous administration. The half-lives at beta  phase were 3.0 to 7.9 h in mice, rats, and rabbits and 24 h in cynomolgus monkeys. There was a linear relationship between the area under the curve extrapolated to infinity [AUC(I)] in mice and dose. Rabbits also exhibited dose proportionality in AUC(I). However, in rats, increasing the dose from 3 to 60 mg/kg of body weight resulted in a 49-fold increase in AUC(I). When the species was changed from mouse to rat, rabbit, or cynomolgus monkey, AUC(I) increased, whereas clearance (CL) decreased. It was concluded that the pharmacokinetics of SCH 27899 in animals varied with species; CL was the highest in mice and rats, followed by rabbits and cynomolgus monkeys.

* Corresponding author. Mailing address: Department of Drug Metabolism and Pharmacokinetics, Schering-Plough Research Institute, 2015 Galloping Hill Rd., Kenilworth, NJ 07033. Phone: (908) 740-3450. Fax: (908) 740-3966. E-mail: chin_chung{at}spcorp.com.

Antimicrobial Agents and Chemotherapy, April 2000, p. 916-919, Vol. 44, No. 4
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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