Publications

Azithromycin is the first of a class of antibiotics classified as azalides. Six ball pythons (Python regius) were given a single dose of azithromycin at 10 mg/kg p.o. and i.v. in a crossover design. Serial blood samples were collected for unchanged azithromycin and to determine, if possible, the structure and number of circulating azithromycin metabolites. After a 4-month wash-out period, the snakes were given azithromycin p.o. as a single dose of 10 mg/kg for the study of azithromycin metabolism and metabolite tissue distribution. Bile, liver, lung, kidney, and skin samples were analyzed for the metabolites identified from the first experiment. Unchanged azithromycin accounted for 80, 68, and 60% of the total material at 12, 24, and 48 h postadministration in plasma, independent of route of administration. At both 24 and 72 h postadministration, azithromycin accounted for 70% of total azithromycin- associated material in bile. In liver and kidney, unchanged azithromycin accounted for 40% of the total azithromycin-associated material; this doubled in lung and skin. Fifteen metabolites were positively or tentatively identified in plasma, bile, or tissues of all snakes. Four of these possible metabolites: 3'-desamine-3-ene-azithromycin, descladinose dehydroxy-2-ene-azithromycin, 3'-desamine-3-ene descladinose-azithromycin, and 3'-N-nitroso,9a-N-desmethyl-azithromycin are unique to this species. Descladinose-azithromycin, 3'-N-desmethyl,9a-N-desmethyl-azithromycin, and 3'-N-desmethyl, 3'-O-desmethyl-azithromycin were the only metabolites identified in skin. Kidney tissue contained a greater number of metabolites than liver tissue, with 3'-N-didesmethyl-azithromycin being identified only in the kidney. Compared with the dog and cat, a greater number of metabolites were identified in ball python plasma. The percentage of unchanged azithromycin in bile is not different between the three species.

This method is the first analytical method for the detection and quantitation of carfentanil and naltrexone at clinically relevant concentrations using liquid chromatography-mass spectrometry. Samples were alkalinized with 100 microl of 1 M NaOH and extracted 2x with 2 ml of toluene. The extractions were combined and dried under N(2) at 40 degrees C in a H(2)O bath. Chromatography was performed using a Zirchrom PBD column and a mobile phase of 30:70 acetonitrile/10 mM ammonium acetate and 0.1 mM citrate (pH=4.4) at a flow rate of 0.3 ml/min. The lower limit of quantitation was 8.5 pg/ml for carfentanil and 0.21 ng/ml for naltrexone.

Lack of approved pharmaceutical agents and/or pharmacokinetic data in the literature for exotic, wildlife, and zoo species is a major issue for veterinarians. These practitioners must take approved agents (veterinary or human) and extrapolate their use to non-approved species with little or no scientific basis to support this decision. There is little information concerning pharmacokinetic parameters for drugs in non-domestic species. Zoo veterinarians often have to formulate the medication(s) into a meal, hoping that the animal will ingest it. Due to lack of patient compliance, the veterinarian may have to resort to other means of drug administration. Additionally, due to the value of these animals, the traditional method of 'trial and error' for treatment selection and resulting compliance is often inappropriate, and lends itself to a mentality where no zoo veterinarian wants to be the first to administer an agent/formulation in an untested species. This review intends to present the current state of zoological pharmacology and the direction it may be heading.