Pharmacokinetics of diphenhydramine following single-dose intravenous and oral administration in non-fasted adult horses.

Diphenhydramine is an H1 receptor antagonist used to control urticaria and other allergic signs caused by type I hypersensitivity reactions in horses (Equus caballus). Limited studies have been conducted on pharmacokinetics of this drug in horses, with no studies involving oral formulations. Our study investigated pharmacokinetics of an oral diphenhydramine formulation compared to intravenous administration in non-fasted adult horses. Six healthy horses underwent a single administration of three different doses of diphenhydramine (1 mg/kg intravenously, 1 mg/kg intragastrically, and 5 mg/kg intragastrically) with a two-week washout period between doses. Bioavailability of intragastric diphenhydramine was less than one percent and six percent for 1 mg/kg and 5 mg/kg intragastric doses, respectively. This poor bioavailability is similar to what is reported in dogs. Two of six horses experienced transient side effects after intravenous diphenhydramine administration, emphasizing the need for determining therapeutic plasma levels in efforts to determine the lowest effective dose minimizing risk of adverse effects. The main conclusion of our study was that oral diphenhydramine at doses up to 5 mg/kg are unlikely to achieve therapeutic plasma levels in adult horses.

Preparation of acetaminophen capsules containing beads prepared by hot-melt direct blend coating.

Twelve hydrophobic coating agents were assessed for their effects on drug release after coating sugar cores by a flexible hot-melt coating method using direct blending. Drug-containing pellets were also produced and used as cores. The cores were coated with single or double wax layers containing acetaminophen (APAP). The harder the wax, the slower the resultant drug releases from single-coated beads. Wax coating can be deposited on cores up to 28% of the beads final weight and reaching 58% with wax and drug. Carnauba-coated beads dissolved in approximately 6 h releasing 80% of the loaded drug. Applying another wax layer extended drug release over 20 h, while still delivering 80% of the loaded drug. When drug-containing pellets (33-58% drug loading) were used as cores, double wax-coated pellets exhibited a near zero-order drug release for 16 h, releasing 80% of the loaded drug delivering 18 mg/h. The simple process of hot-melt coating by direct blending of pellet-containing drug-coated formulations provides excellent options for immediate and sustained release formulations when higher lipid coating or drug loading is warranted. Predicted plasma drug concentration time profiles using convolution and in vitro drug release properties of the beads were performed for optimal formulations.