Pharmacokinetic-Pharmacodynamic Study of Ampicillin-Cloxacillin Combination in Indian Thoroughbred Horses (Equus caballus) and Safety Evaluation of the Computed Dosage Regimen.

The research article concerns the study of the pharmacokinetics and pharmacodynamics of the ampicillin-cloxacillin combination in Indian thoroughbred horses, with an objective of identifying an appropriate and safe dosing strategy.

Understanding Pharmacokinetics and Pharmacodynamics

• In the pharmacological universe, pharmacokinetics (PK) and pharmacodynamics (PD) play vital roles. Pharmacokinetics involves the study of how a drug moves through a body, including its absorption, distribution, metabolism, and excretion. Pharmacodynamics, on the other hand, investigates how a drug affects the body, including the biochemical and physiological effects of the drug.

Research Methodology

• Six clinically presented Indian thoroughbred horses were administered the ampicillin-cloxacillin combination as a single intravenous dose of 10 mg.kg (5 mg.kg of ampicillin and 5 mg.kg of cloxacillin).
• The drug concentrations in plasma were determined using a technique called High Performance Liquid Chromatography (HPLC), which is commonly used in biochemistry and analytical chemistry to identify, quantify, and purify individual components of a mixture.
• The pharmacokinetic parameters were derived through a non-compartmental analysis using software named WinNonlin.
• The Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) of the ampicillin-cloxacillin combination were determined against strains of Escherichia coli and Staphylococcus aureus, which were grown in Muller Hinton Broth, using the broth microdilution method.

Results

• The researchers discovered specific measurements known as the ‘Area Under the Curve’ (AUC), the ‘Mean Residence Time’ (MRT), and ‘Clearance’ (Cl), for both ampicillin and cloxacillin.
• The PK-PD integration led to the conclusion that to maintain a minimum inhibitory concentration time (also known as %T > MIC) value 50% for bacteria with MIC ≤ 0.4 µg.ml, the appropriate dosage regimen of ampicillin-cloxacillin combination for thoroughbred horses would be 15 mg.kg (that is, 7.5 mg.kg of ampicillin and 7.5 mg.kg of cloxacillin). This dose should be repeated every 12 hours.

Safety Evaluation

• The safety profile of this suggested regimen was established as it did not significantly alter any of the 16 biochemical or haematological parameters that were studied. This indicated that the proposed dosage was safe for the subject horses.