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Pharmacokinetics of marbofloxacin in two male and four female adult ball pythons (Python regius) was determined after i.v. and p.o. administration of a single dose. Using a crossover design, each snake was given a single 10 mg/kg dose of marbofloxacin i.v. and p.o. Blood samples were collected prior to and 0.5, 1, 1.5, 3, 6, 12, and 24 hr after marbofloxacin administration. Marbofloxacin was quantitated by use of liquid chromatography-mass spectrometry. Following p.o. administration, marbofloxacin had a peak plasma concentration (Cmax) of 9.40 microg/ml and a time to Cmax (Tmax) of 9.0 hr. Based on the plasma pharmacokinetics generated in this study and pending any further studies to evaluate potential toxicity and multi-dose pharmacokinetics, we suggest a dosage for marbofloxacin in ball pythons of 10 mg/kg p.o. at least every 48 hr, depending on the sensitivity of the pathogen and as a basis for further research.

OBJECTIVE: To determine the pharmacokinetics of marbofloxacin after single IV and orally administered doses in blue and gold macaws.

ANIMALS: 10 healthy blue and gold macaws.

PROCEDURES: In a crossover study, marbofloxacin (2.5 mg/kg) was administered orally (via crop gavage) to 5 birds and IV to 5 birds. Blood samples were obtained at 0, 0.5, 1, 3, 6, 12, 24, 48, 72, and 96 hours after marbofloxacin administration. After a 4-week washout period, the study was repeated, with the first 5 birds receiving the dose IV and the second 5 birds receiving the dose orally. Serum marbofloxacin concentrations were quantitated by use of a validated liquid chromatography-mass spectrometry assay.

RESULTS: After oral administration, mean +/- SD area under the curve was 7.94 +/- 2.08 microg.h/mL, maximum plasma concentration was 1.08 +/- 0.316 microg/mL, and bioavailability was 90.0 +/- 31%. After IV administration of marbofloxacin, the apparent volume of distribution was 1.3 +/- 0.32 L/kg, plasma clearance was 0.29 +/- 0.078 L/h/kg, area under the curve was 9.41 +/- 2.84 microg.h/mL, and the harmonic mean terminal half-life was 4.3 hours.

CONCLUSIONS AND CLINICAL RELEVANCE: Single IV and orally administered doses of marbofloxacin were well tolerated by blue and gold macaws. The orally administered dose was well absorbed. Administration of marbofloxacin at a dosage of 2.5 mg/kg, PO, every 24 hours may be appropriate to control bacterial infections susceptible to marbofloxacin in this species.

Interspecies scaling is a useful tool for the prediction of pharmacokinetic parameters from animals to humans, and it is often used for estimating a first-time in human dose. However, it is important to appreciate the mathematical underpinnings of this scaling procedure when using it to predict pharmacokinetic parameter values across animal species. When cautiously applied, allometry can be a tool for estimating clearance in veterinary species for the purpose of dosage selection. It is particularly valuable during the selection of dosages in large zoo animal species, such as elephants, large cats and camels, for which pharmacokinetic data are scant. In Part I, allometric predictions of clearance in large animal species were found to pose substantially greater risks of inaccuracies when compared with that observed for humans. In this report, we examine the factors influencing the accuracy of our clearance estimates from the perspective of the relationship between prediction error and such variables as the distribution of body weight values used in the regression analysis, the influence of a particular observation on the clearance estimate, and the 'goodness of fit' (R(2)) of the regression line. Ultimately, these considerations are used to generate recommendations regarding the data to be included in the allometric prediction of clearance in large animal species.

The pharmacokinetic parameters of carfentanil and naltrexone were determined in the common eland (Taurotragus oryx). Six adult females were immobilized with xylazine (0.23 +/- 0.03 mg/kg i.m.) and carfentanil (0.0169 +/- 0.0005 mg/kg i.m.) for a 45-min period, during which time routine health care procedures were performed. Heart and respiration rates and body temperatures were monitored throughout the immobilization period. A single intramuscular injection of naltrexone (1.66 +/- 0.08 mg/kg i.m.) was sufficient for reversal. The eland were intermittently restrained in a hydraulic squeeze chute for serial blood sample collection via jugular venipuncture during immobilization and up to 48 hr post-immobilization. The quantification of carfentanil and naltrexone in the plasma was performed by liquid chromatography and mass spectroscopy methods. Carfentanil was rapidly absorbed following administration, with the peak plasma concentration (C(max)) at 13.8 min. Naltrexone was readily absorbed and reached C(max) at 23.4 +/- 16.8 min after administration. All animals stood 2.7 +/- 2.2 min after naltrexone administration. Carfentanil has a half-life of 7.7 hr, whereas naltrexone has a much shorter half-life of 3.7 hr. Although respiratory rates appeared to fluctuate widely among animals, heart rates and body temperature remained stable throughout the immobilization. Renarcotization was not noted as a major complication.

Interspecies scaling is a useful tool for the prediction of pharmacokinetic parameters from animals to humans, and it is often used for estimating a first-time in human dose. The knowledge of pharmacokinetics in veterinary species is important for dosage selection, particularly in the treatment of large zoo animal species, such as elephants, giant cats and camels, for which pharmacokinetic data are scant. Therefore, the accuracy in clearance predictions in large animal species, with and without the use of correction factors (rule of exponents), and the impact of species selection in the prediction of clearance in large animal species was examined. Based upon this analysis, it was determined that there is a much larger risk of inaccuracies in the clearance estimates in large animal species when compared with that observed for humans. Unlike in humans, for large animal species, correction factors could not be applied because there was no trend between the exponents of simple allometry and the appropriate correction factor for improving our predictions. Nevertheless, we did see an indication that the exponents of simple allometry may alert us as to when the predicted clearance in the large animal may be underestimated or overpredicted. For example, if a large animal is included in the scaling, the predicted clearance in a large animal should be considered overestimated if the exponent of simple allometry is >1.3. Despite the potential for extrapolation error, the reality is that allometric scaling is needed across many veterinary practice situations, and therefore will be used. For this reason, it is important to consider mechanisms for reducing the risk of extrapolation errors that can seriously affect target animal safety, therapeutic response, or the accuracy of withdrawal time predictions.

Three captive loggerhead sea turtles, Caretta caretta, were used in four trials, one i.v. and three i.m., to determine the pharmacokinetic properties of a single dose of ticarcillin. For the i.v. study, each turtle received a single 50 mg/kg dose and blood samples were collected at 0, 0.5, 1, 2, 4, 6, 8, and 12 hr and at 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, and 14 days after administration. For the i.m. study, each turtle received one of three dosages (25, 50, or 100 mg/kg) in a randomized complete block design and blood samples were collected at the same time intervals. Each trial was separated by a minimum of 28 days to allow for complete drug clearance. Drug concentration in plasma was determined by a validated liquid chromatography-mass spectrometry assay. For the i.v. study, the elimination half-life was 5.0 hr. The apparent volume of distribution and plasma clearance were 0.17 L/kg and 0.0218 L/hr/kg, respectively. For the i.m. study, mean time to maximum plasma concentrations ranged from 1.7 ( +/- 0.58) hr in the 50 mg/kg group to 3.7 (+/- 2.5) hr in the 100 mg/kg group. Mean bioavailability ranged from 45% ( +/- 15%) in the 50 mg/kg group to 58% (+/- 12%) in the 100 mg/kg group, and the mean residence time ranged from 7.5 ( +/- 2.6) hr in the 25 mg/kg group to 16 (+/- 6.8) hr in the 100 mg/kg group. Two turtles had slight alanine aminotransferase elevations that were not clinically apparent at two different dosages, but otherwise, blood chemistries were unaffected. Possible i.m. dosage regimens for loggerhead sea turtles are 50 mg/kg q24 hr or 100 mg/kg q48 hr. Liver enzymes should be monitored during treatment.

Captive elephants are prone to infections of the feet, lungs, and skin. Often treatment regimens are established with no pharmacokinetic data on the agents being used for treatment in these species. A pharmacokinetic study using ceftiofur (1.1 mg/kg) was conducted in four adult female captive Asian elephants (Elephas maximus) at Busch Gardens in Tampa, Florida. Elephants were given both i.v. and i.m. administrations in a complete crossover design with a 3-week washout period between treatments. Blood samples were collected prior to drug administration and at 0.33, 0.67, 1, 1.5, 2, 4, 8, 12, 24, 48 and 72 h postadministration. Ceftiofur analysis was performed using a validated liquid chromatography/mass spectrophotometric (LC/MS) assay. Plasma concentrations for the i.m. samples were lower than expected. The mean C(max) following i.m. administration was 1.63 microg/mL with a corresponding T(max) of 0.55 h. Following i.v. administration, the median V(d(ss)) was 0.51 L/kg and a median Cl(p) of 0.069 L/kg/h. Mean i.m. bioavailability was 19%. The results indicate that ceftiofur used at 1.1 mg/kg i.m. could be useful in elephants when given two to three times a day or alternatively, 1.1 mg/kg i.v. once daily, depending upon the MIC of the pathogen.

Azithromycin is classified as an azalide, a subclass of macrolide antimicrobials with a broad spectrum of activity in vitro against many potential bacterial pathogens including spirochetes, anaerobes, and Chlamydia trachomatis. Because of limited data on the use of azithromycin in avian medicine, this study was designed to determine the pharmacokinetics of azithromycin in blue and gold macaws (Ara ararauna), a species commonly seen in clinical practice. Azithromycin (10 mg/kg) was administered via crop lavage to five birds and intravenously to five birds, and blood samples were obtained at 0, 0.5, 1, 3, 6, 12, 24, 48, 72, and 96 hr post-azithromycin administration. Following a 4-wk washout period, the study was repeated with a complete crossover study performed. Concentration of azithromycin in plasma samples was quantified using a validated liquid chromatography/mass spectrometry assay. Pharmacokinetic parameters were determined using noncompartmental analysis. Based on the pharmacokinetic data generated from this study, a starting dose of azithromycin at 10 mg/kg p.o. every 48 hr for susceptible bacterial infections in blue and gold macaws is recommended.