Pharmacokinetics of cefazolin in guinea pigs.
The occurrence of antibiotic-related enterocolitis in guinea pigs restricts the use of many common antibiotics in this species. Cephaloridine, an antibiotic frequently recommended for this species, is no longer available and a substitute has yet to be explored. In this study, the potential therapeutic efficacy of cefazolin, also a first generation cephalosporin, was evaluated in guinea pigs by assessing pharmacokinetics, toxicity and the minimal inhibitory concentration for selected animal pathogens. Pharmacokinetics and toxicity were evaluated in four phases: single intramuscular injections, multiple intramuscular injections over 30 hours, multiple intramuscular injections over 5 days, and serum-protein binding studies. Antibiotic-related enterocolitis and irritation at the injection site occurred following high (100 mg/kg) repeated doses. At all dose levels, blood values exceeded the minimum inhibitory concentration for Bordetella bronchiseptica for only 1 hour postinjection. For Streptococcus and Staphylococcus sp., the drug half-life was 0.5 hours with peak concentrations occurring within 0.25 hours of injection. The volume of distribution of 0.5 l/kg indicated that there was extensive tissue distribution. Serum protein binding was approximately 85%. The short half-life and rapid plasma clearance rate (10.4 ml/min/kg) indicated that cefazolin is eliminated very rapidly from the guinea pig and may be of questionable therapeutic value.
Department of Comparative Medicine, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
P E
PE
Fritz
W J
WJ
Hurst
W J
WJ
White
C M
CM
Lang
D000818:Animals; D001884:Bordetella / Q000187:drug effects; D002437:Cefazolin / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000633:toxicity; D005260:Female; D006168:Guinea Pigs / Q000378:metabolism*; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D013211:Staphylococcus aureus / Q000187:drug effects; D013291:Streptococcus / Q000187:drug effects
D002437:Cefazolin