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

Abstact Intravenous (iv), subcutaneous (sq), and topical (tp) lidocaine was administered to six horses in a cross‐over, randomized design study. Samples were collected for up to 72 hr. Compartmental models were used to investigate the pharmacokinetics of (LD) and its metabolites 3‐hydroxylidocaine (3‐OH), 4‐hydroxylidocaine (4‐OH), and monoethylglycinexylidide (MEGX). Metabolites 3‐OH and 4‐OH were present in conjugated forms, whereas LD and metabolite MEXG were present primarily in the un‐conjugated form. Plasma concentrations of LD after iv administration (100 mg) were described by three‐compartment model with an additional three compartments to describe the elimination of metabolites. Median (range) elimination micro‐constants (Ke) for LD, 3‐OH, 4‐OH, and MEXG were 4.12 (2.62–6.23), 1.25 (1.10–2.15), 1.79 (1.22–2.39), and 1.69 (1.03–1.99)/hr, respectively. Median (range) values of alpha (t½α), beta (t½β), and gamma (t½γ) half‐lives were 0.08 (0.07–0.13), 0.57 (0.15–1.25), and 4.11 (0.52–7.36) hr. Plasma concentrations of LD after sq (200 mg) administration were described by absorption and two‐compartment elimination model. The median (range) of the LD absorption half‐life (t½ab) was 0.47 (0.29–0.61) hr. The Ke for LD, 3‐OH, 4‐OH, and MEXG was 3.91 (1.48–9.25), 1.00 (0.78–1.08), 1.76 (0.96–2.11), and 1.13 (0.69–1.33)/hr. The median (range) of t½α and t½β was 0.15 (0.06–0.27) and 3.04 (2.53–6.39) hr. Plasma concentrations of LD after tp (400 mg) application were described by one‐compartment model with a t½ab of 8.49 (5.16–11.80) hr. The Ke for LD, 3‐OH, and MEXG was 0.24 (0.10–0.81), 0.41 (0.08–0.93), and 0.38 (0.26–1.14)/hr.