Pharmacokinetics of pimobendan following oral administration to New Zealand White rabbits (Oryctolagus cuniculus).

OBJECTIVE: To determine the pharmacokinetics and potential adverse effects of pimobendan after oral administration in New Zealand White rabbits (Ocytolagus cuniculi). ANIMALS: 10 adult sexually intact (5 males and 5 females) rabbits. PROCEDURES: 2 pilot studies were performed with a pimobendan suspension or oral tablets. Eight rabbits received 7.5 mg of pimobendan (mean 2.08 mg/kg) suspended in a critical care feeding formula. Plasma concentrations of pimobendan and O-demethylpimobendan (ODMP) were measured, and pharmacokinetic parameters were calculated for pimobendan by noncompartmental analysis. Body weight, food and water consumption, mentation, urine, and fecal output were monitored. RESULTS: Mean ± SD maximum concentration following pimobendan administration was 15.7 ± 7.54 ng/mL and was detected at 2.79 ± 1.25 hours. The half-life was 3.54 ± 1.32 hours. Plasma concentrations of pimobendan were detectable for up to 24 hours. The active metabolite, ODMP, was detected in rabbits for 24 to 36 hours. An adverse event occurred following administration of pimobendan in tablet form in 1 pilot study, resulting in death secondary to aspiration. No other adverse events occurred. CLINICAL RELEVANCE: Plasma concentrations of pimobendan were lower than previously reported for dogs and cats, despite administration of higher doses, and had longer time to maximum concentration and half-life. Based on this study, 2 mg/kg of pimobendan in a critical care feeding formulation should maintain above a target plasma concentration for 12 to 24 hours. However, further studies evaluating multiple-dose administration as well as pharmacodynamic studies and clinical trials in rabbits with congestive heart failure are needed to determine accurate dose and frequency recommendations.

Therapeutic effects of bezafibrate and gemfibrozil in hyperlipoproteinaemia type IIa and IIb.

Fifty-nine patients with hyperlipoproteinaemia Type IIa and IIb who had failed to respond to 1-month's dietary therapy were treated over a 4-month period with either bezafibrate (600 mg/day) or gemfibrozil (1200 mg/day) in addition to their diet. Fasting serum lipid (cholesterol, HDL-cholesterol and triglycerides) and blood glucose levels were measured on entry and at monthly intervals, and routine laboratory investigations were carried out before and after treatment to monitor hepatic, renal and haematic tolerance. The results showed that whilst both drugs produced significant reductions from baseline in total cholesterol, LDL-cholesterol and triglyceride levels from Day 30 onwards, the reductions were more marked in the bezafibrate group. There was a trend for HDL-cholesterol levels to increase. Fasting blood glucose levels decreased significantly in the bezafibrate group and to a greater extent than in patients on gemfibrozil. Only 1 patient on bezafibrate did not tolerate bezafibrate whereas 13 patients on gemfibrozil reported side-effects, mainly gastro-intestinal, and 4 had to withdraw from the study during the first or second month.