
Aldawsari, Mohammed F.; Lau, Vivian W.; Babu, Ramapuram J.; Arnold, Robert D.; Platt, Simon R.
Pharmacokinetic evaluation of novel midazolam gel formulations following buccal administration to healthy dogs
Източник: AMERICAN JOURNAL OF VETERINARY RESEARCH
Година на издаване: 2018 г.
Брой: 79, 1
Страници: p. 73-82
Държател: TUN
Сигнатура: А 182
Ключови думи: dogs
Анотация: OBJECTIVE To determine the physiochemical properties and pharmacokinetics of 3 midazolam gel formulations following buccal administration to dogs. ANIMALS 5 healthy adult hounds. P ROCEDURES In phase I of a 2-phase study, 2 gel formulations were developed that contained 1 percent midazolam in a poloxamer 407 (PI) or hydroxypropyl methylcellulose (HI) base and underwent rheological and in vitro release analyses. Each formulation was buccally administered to 5 dogs such that 0.3 mg of midazolam/kg was delivered. Each dog also received midazolam hydrochloride (0.3 mg/kg, IV). There was a 3-day interval between treatments. Blood samples were collected immediately before and at predetermined times for 8 hours after drug administration for determination of plasma midazolam concentration and pharmacokinetic analysis. During phase 2, a gel containing 2 percent midazolam in a hydroxypropyl methylcellulose base (H2) was developed on the basis of phase I results. That gel was buccally administered such that midazolam doses of 0.3 and 0.6 mg/kg were delivered. Each dog also received midazolam (0.3 mg/kg, IV). All posttreatment procedures were the same as those for phase I. RESULTS The HI and H2 formulations had lower viscosity, greater bioavailability, and peak plasma midazolam concentrations that were approximately 2-fold as high, compared with those for the PI formulation. The mean peak plasma midazolam concentration for the H2 formulation was 187.0 and 106.3 ng/mL when the midazolam dose administered was 0.6 and 0.3 mg/kg, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that buccal administration of gel formulations might be a viable alternative for midazolam administration to dogs



