Pharmacokinetics of minocycline in domestic cats

Abstract

Objectives: Recently, the increased cost and decreased availability of doxycycline has sparked an interest in using minocycline as an alternative. The purpose of this study was to determine the pharmacokinetics of minocycline in domestic cats in order to facilitate dosage decisions.

Methods: Purpose-bred, young adult cats were administered a single dose of either intravenous (IV; n = 4; 5 mg/kg) or oral (n = 6; 50 mg/cat) minocycline. Blood was collected from each at intervals up to 24 h afterwards. Minocycline was measured using high performance liquid chromatography with ultraviolet detection. A one-compartment pharmacokinetic model was fit to the oral data and a two-compartment model to the IV data via a computer program. Plasma protein binding was measured by fortifying blank plasma from untreated healthy cats with minocycline at two concentrations and applying an ultracentrifugation method.

Results: Two cats became transiently lethargic and tachypneic during IV drug infusion. One cat vomited 6.0 h after infusion, and two cats vomited either 1.5 h or ~5.0 h after oral drug administration. The mean oral dose administered was 13.9 ± 0.47 mg/kg. Oral bioavailability was approximately 62%. Plasma protein binding was 60% at 5 µg/ml and 46% at 1 μg/ml. After IV administration, elimination half-life (t(½)), apparent volume of distribution at steady-state, and systemic clearance were 6.7 h (coefficient of variation [CV] 14.4%), 1.5 l/kg (CV 34.5%) and 2.9 ml/kg/min (CV 40.8%), respectively. After oral administration the terminal t(½) and peak concentration (Cmax) were 6.3 h (CV 9%) and 4.77 µg/ml (CV 36%), respectively.

Conclusions and relevance: Because most bacteria will have a minimum inhibitory concentration of ⩽0.5 μg/ml, an oral dose of 8.8 mg/kg q24h would be adequate to meet pharmacokinetic-pharmacodynamic targets after adjusting for protein binding. Although some gastrointestinal upset may occur, one 50 mg capsule orally q24h would provide appropriate dosing for most cats.

Figure 1

Plasma concentrations of minocycline in cats after intravenous (IV) injection of 5 mg/kg (n = 4) and oral administration of 13.94 mg/kg (n = 6). The points represent mean ± SD concentrations, with lines overlaid representing the fitted lines from the pharmacokinetic model