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.
Fritz
P E
PE
Department of Comparative Medicine, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
Hurst
W J
WJ
White
W J
WJ
Lang
C M
CM
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