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.

Concentrations of Retinol and α-Tocopherol in Tissue Samples From Anna's Hummingbirds (Calypte anna).

Retinol (vitamin A) and α-tocopherol (vitamin E) concentrations were measured in tissue samples (liver, heart, pectoral muscle, and brain) from Anna's Hummingbirds (Calypte anna). Hummingbirds were after-hatch year birds that were sourced from various rehabilitation centers throughout California. Tissues samples were analyzed using high-performance liquid chromatography (HPLC). Minimum, maximum, mean, standard deviation (SD), and median ppm concentrations were calculated for each vitamin and tissue sample type. A novel analytical method was developed to analyze small mass tissue samples, with the smallest sample mass being 0.05 g for which analysis can be performed. Mean ± standard deviation (SD) concentrations of retinol in hummingbird livers, hearts, and pectoral muscle samples were 269.0 ± 216.9 ppm, 1.8 ± 2.2 ppm, and 0.3 ± 0.1 ppm, respectively. Mean ± SD α-tocopherol concentrations were 6.9 ± 4.6 ppm, 5.5 ± 4.0 ppm, 3.7 ± 2.2 ppm, and 9.1 ± 3.2 ppm for liver, heart, pectoral muscle, and brain samples, respectively. Vitamin concentrations from varying tissue types were compared to determine which were best associated with liver concentrations, the most commonly analyzed tissue for these vitamins. For both retinol and α-tocopherol, heart samples were most strongly associated with the liver samples. The results of this study provide baseline retinol and α-tocopherol concentrations in different tissue types from Anna's hummingbirds. These baseline values may be utilized in conservation efforts to avoid hypervitaminosis and hypovitaminosis of rehabilitated and/or captive hummingbirds by providing guidelines for nutritional targets which could be assessed on post-mortem examinations. Post-mortem examination of birds and measurement of vitamin concentrations in tissues may allow for dietary changes that aid captive hummingbirds.