title: Pharmacokinetics of rifampin in adult sheep.
abstract: Pharmacokinetics and bioavailability of rifampin in adult sheep were investigated by use of high-performance liquid chromatography for determination of serum concentrations. Eight adult ewes were given rifampin PO at the rate of 50 mg of rifampin/kg of body weight. Three weeks after the first experiment, the sheep were given rifampin PO and IV at the rate of 20 mg/kg in a cross-over design, with 1 week between treatments. Serum obtained over a 36-hour period was analyzed for rifampin and a potential metabolite, 25-desacetyl-rifampin, using reverse-phase chromatography with UV detection at 254 nm. Data were analyzed by compartmental and noncompartmental models. Analysis by the noncompartmental model of rifampin serum concentrations after IV administration yielded a mean +/- SD total body clearance of 1.16 +/- 0.21 ml/min/kg, apparent volume of distribution at steady state of 0.45 +/- 0.06 L/kg, and terminal elimination rate constant of 0.15 +/- 0.04 hour-1. The harmonic mean of the elimination half-life was 4.56 hours. Because of incomplete and continuing absorption, bioavailability was extremely variable after oral administration. Desacetyl-rifampin was not detected. On the basis of pharmacokinetic values, serum concentrations measured in this study, and published minimal inhibitory concentrations, the dosage of 20 mg of rifampin/kg, PO, every 24 hours should provide adequate serum concentrations for treatment of rifampin-susceptible bacterial infections in sheep.
authors.affiliation: Department of Veterinary Physiology, College of Veterinary Medicine, Ohio State University, Columbus 43210.
authors.forename: A D
authors.initials: AD
authors.lastname: Jernigan
authors.forename: G D
authors.initials: GD
authors.lastname: St Jean
authors.forename: D M
authors.initials: DM
authors.lastname: Rings
authors.forename: R A
authors.initials: RA
authors.lastname: Sams
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006207:Half-Life; D011897:Random Allocation; D012293:Rifampin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012756:Sheep / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D012293:Rifampin