Pharmacokinetics and bioavailability of cephalothin in horse mares.

The research investigates the pharmacokinetics (how a drug moves through the body) and bioavailability (amount of the drug that enters circulation) of the antibiotic cephalothin when administered to female horses either intravenously (IV) or intramuscularly (IM). The research found that cephalothin is rapidly metabolized and eliminated from the body, with the half-life and bioavailability significantly different between the two administration routes.

Study Methodology

• The study involved 6 horse mares, each given a dose of cephalothin at 11 mg/kg of body weight either intravenously (IV) or intramuscularly (IM).
• The researchers measured various pharmacokinetic parameters such as half-life, residence time, clearance, volume of distribution, and protein binding.
• The peak plasma concentrations of cephalothin and desacetylcephalothin (a metabolite of cephalothin) were also measured after administration.

Results: Intravenous Administration

• When cephalothin was given IV, it had a rapid dispotion phase characterised by a half-life of 2.89 minutes, followed by a slower elimination phase with a half-life of 14.7 minutes.
• The average residence time of cephalothin in the body was 10.6 minutes.
• The total plasma clearance of cephalothin, looking at how much cephalothin was removed from plasma per unit time, averaged 13.6 ml/min/kg, with both metabolism and renal elimination contributing.
• The renal clearance of cephalothin (amount of cephalothin cleared from the body through kidneys) averaged 1.32 ml/min/kg, contributing to around 10.1% of elimination.
• The volume at which cephalothin was distributed throughout the body, when in a steady state, averaged 151 mg/kg.
• About 17.9% of cephalothin in the plasma was bound to proteins.

Metabolization to Desacetylcephalothin

• Cephalothin was metabolized rapidly into desacetylcephalothin.
• The peak concentration of desacetylcephalothin in plasma was observed within 5 minutes of IV dose and averaged 22.9 micrograms/ml.
• The half-life of desacetylcephalothin in plasma was measured as 41.6 minutes.
• The average renal clearance of desacetylcephalothin was 4.49 ml/min/kg.
• An average of 33.9% of the administered dose was recovered in urine as desacetylcephalothin.

Results: Intramuscular administration

• The peak plasma concentration of cephalothin achieved after IM administration was 11.3 micrograms/ml.
• The terminal half-life after IM administration was found to be longer than after IV administration, at 47.0 minutes.
• The bioavailability of cephalothin, which looks at how much cephalothin reaches systemic circulation, ranged from 38.3% to 93.1%, with an average of 65.0%.