A review of the pharmacology, pharmacokinetics and behavioral effects of procaine in thoroughbred horses.

The research paper focuses on studying the pharmacology, pharmacokinetics, and behavioral effects of procaine in thoroughbred horses. Since procaine possesses local anaesthesia and central stimulant properties, it’s banned from racing horses. The study explores the absorption, distribution, and elimination of procaine based on different methods of administration.

Pharmacokinetics of Procaine

• Procaine was administered intravenously at a dosage of 2.5 mg/Kg in thoroughbred mares and its presence in the bloodstream was analysed. The plasma levels of procaine were reduced rapidly half within 5 minutes, and then at a slower pace with a half-life of 50.2 minutes.
• A two-compartment open model was used to fit these kinetics, which gave an estimated apparent Vdbeta (volume of distribution in the beta phase) for procaine in the horse at around 3,500 liters. After considering that procaine was around 45% bound to equine plasma protein this suggests a true Vdbeta of about 6,500 liters.

Procaine Distribution after Subcutaneous and Intramuscular Injections

• After procaine was injected subcutaneously at a dosage of 3.3 mg/Kg, plasma levels peaked at around 400 ng/ml and then lessened with a half-life of approximately 75 minutes. These data were also well matched by the two compartment open model when modified to include a simple first order absorption.
• After intramuscular injection of procaine penicillin (33,000 I.U./Kg), plasma levels hit a peak around 270 ng/ml and then reduced with a half-life of about 9 hours. These data were approximated using the modified two compartment model along with an assumed first order rate constant for procaine absorption.
• Following intramuscular injection of procaine HC1 (10 mg/Kg), plasma levels of procaine spiked quickly at around 600 ng/ml but thereafter dropped sluggishly (+ 1/2 = 2 hours). Modelling this intramuscular data was challenging, but an approximation was obtained assuming the existence of two intramuscular drug compartments.

Pharmacokinetics after Intra-Articular Administration

• After intra-articular administration of procaine (0.33 mg/Kg), peak plasma levels of the drug reached about 17 ng/ml before declining with a half-life of roughly 2 hours. These data were not modeled.