Pharmacokinetics of intravenous, subcutaneous, and topical administration of lidocaine hydrochloride and metabolites 3-hydroxylidocaine, monoethylglycinexylidide, and 4-hydroxylidocaine in horse.

This research evaluates the metabolism and distribution (pharmacokinetics) of the drug Lidocaine and its metabolites in horses when given intravenously, subcutaneously, and as a topical application. It finds that the drug is handled differently based on the route of administration and that certain metabolites of the drug are more prevalent in specific forms of administration.

Research Method

• This study used six horses and applied a cross-over, randomized design study. Lidocaine and its metabolites were administered through three different routes: Intravenous (iv), Subcutaneous (sq), and Topical (tp).
• Samples for analysis were collected at intervals stretching to 72 hours after administration. The samples were analysed to determine the concentration of Lidocaine and the metabolites – 3-hydroxylidocaine (3-OH), 4-hydroxylidocaine (4-OH), and monoethylglycinexylidide (MEGX).
• The researchers then used compartmental models to scrutinize the pharmacokinetics of Lidocaine and its metabolites.

Findings

• The 3-OH and 4-OH metabolites of Lidocaine were found to be present in conjugated forms, whereas Lidocaine and the MEXG metabolite were primarily non-conjugated.
• The plasma concentration of Lidocaine (100 mg administration) followed a three-compartment model with an additional three compartments describing the elimination of the metabolites. The median elimination constants (K) for Lidocaine, 3-OH, 4-OH, and MEXG were reported.
• In case of Subcutaneous administration (200 mg), a two-compartment elimination model with absorption described the plasma concentrations of Lidocaine. The absorption half-life of Lidocaine and elimination constant of Lidocaine and its metabolites were determined.
• Topical application of Lidocaine (400 mg) showed a single-compartment model behavior with a determinedHalf-life. The elimination constant for Lidocaine, 3-OH, and MEXG in this method of administration was reported.
• These findings suggest distinct pharmacokinetic behaviors for lidocaine and its metabolites based on the route of drug administration.

Significance of the Study

• The study sheds light on the pharmacokinetics of Lidocaine when administered through different routes in horses. This information is important for determining the effective dose and route of administration in clinical settings.
• The research could also assist in predicting potential side effects and drug interactions, as the presence and ratio of different metabolites can differ based on the mode of administration.