DISTRIBUTION OF CHLORAMPHENICOL IN THE BOVINE GENITAL TRACT AND PHARMACOKINETIC STUDIES OF FLORFENICOL IN CATTLE

The objectives were to investigate selected aspects of the distribution of chloramphenicol (CAP) in the bovine genital tract and to conduct preliminary pharmacologic studies with florfenicol (FLO), a fluorinated analogue of thiamphenicol, in cattle.;After 8 hours' continuous intravenous (IV) infusion of CAP to 7 postpartum cows, steady state plasma-to-genital tissue ratios of CAP were approximately 3. After intrauterine infusion of 20 mg CAP/kg to 3 postpartum cows, approximately 40 percent of the dose was absorbed into the bloodstream. Tissue concentrations were high at 8 hours postdosing in tissues lining the uterine lumen but were below desired therapeutic concentrations in the myometrium of 2 of the cows.;Eighty cows with retained fetal membranes (RFM) were assigned to receive one of the following treatments: (1) removal of membranes only; (2) removal plus CAP; (3) nonremoval; (4) nonremoval plus CAP. CAP treatment consisted of 5 g administered IU twice daily for 3 days. The majority of cows in all groups acquired endometritis, although CAP reduced the prevalence and severity of the disease. There was no difference between treated groups and healthy herdmates in subsequent reproductive performance (days open, services per conception).;A quantitative assay for FLO in plasma was developed and validated on a high performance liquid chromatographic (HPLC) system.;The pharmacokinetics of FLO determined after IV administration of 50 mg FLO/kg to 5 cows were best described by a three-compartment model. The half-life of the drug was 3.2 hours and the volume of distribution was 0.67 L/kg.;FLO was approximately 18 percent bound to plasma proteins as determined by equilibrium dialysis and ultrafiltration.;In an in vitro system, 5, 125, or 1000 ug/ml of CAP had no effect on phagocytosis of ('32)P-labeled Staphylococcus aureus by blood neutrophils from 6 cows. The same concentrations of FLO all significantly reduced phagocytosis although the percent change was generally small (<10%). There was significant variation between neutrophils from different cows. The clinical relevance of this effect of FLO remains to be determined.