Oral bioavailability and pharmacokinetic characteristics of ketoprofen enantiomers after oral and intravenous administration in Asian elephants (Elephas maximus)

OBJECTIVE: To assess oral bioavailability (F) and pharmacokinetic characteristics of the R- and S-enantiomers of ketoprofen administered IV and orally to captive Asian elephants (Elephas maximus). ANIMALS: 5 adult Asian elephants. PROCEDURE: Elephants received single treatments of racemic ketoprofen at a dose of 2.2 mg/kg, administered IV and orally, in a complete crossover design. Blood samples were collected at intervals during the 24 hours following treatment. At least 4 weeks elapsed between drug administrations. Samples were analyzed for R- and S-ketoprofen with a validated liquid chromatography-mass spectroscopic assay. Pharmacokinetic parameters were determined by use of noncompartmental analysis. RESULTS: The enantiomers of ketoprofen were absorbed well after oral administration, with median F of 101% for R-ketoprofen and 85% for S-ketoprofen. Harmonic mean half-life ranged from 3.8 to 5.5 hours, depending on route of administration and enantiomer. The area under the concentration-time curve, mean residence time, apparent volume of distribution, plasma clearance, and maximum plasma concentration values were all significantly different between the 2 enantiomers for both routes of administration. CONCLUSIONS AND CLINICAL RELEVANCE: Ketoprofen has a long terminal half-life and complete absorption in this species. Based on the pharmacokinetic data, a dosage of ketoprofen of 1 mg/kg every 48 hours to 2 mg/kg every 24 hours, PO or IV, is recommended for use in Asian elephants, although the safety and efficacy of ketoprofen during long-term administration in elephants have not been determined.     

Pharmacokinetics and tissue concentrations of azithromycin in ball pythons (Python regius)

OBJECTIVE: To determine pharmacokinetics and tissue concentrations of azithromycin in ball pythons (Python regius) after IV or oral administration of a single dose. ANIMALS: 2 male and 5 female ball pythons. PROCEDURES: Using a crossover design, each snake was given a single dose of azithromycin (10 mg/kg) IV. After a 4-week washout period, each snake was given a single dose of azithromycin (10 mg/kg) orally. Blood samples were collected prior to dose administration and 1, 3, 6, 12, 24, 48, 72, and 96 hours after azithromycin administration. Azithromycin was quantitated by use of liquid chromatography-mass spectrometry. RESULTS: After IV administration, azithromycin had an apparent volume of distribution of 5.69 L/kg and a plasma clearance of 0.19 L/h/kg. Harmonic means for the terminal half-life were 17 hours following IV administration and 51 hours following oral administration. Mean residence times were 37 and 94 hours following IV and oral administration, respectively. Following oral administration, azithromycin had a peak plasma concentration (Cmax) of 1.04 microg/mL, a time to Cmax of 8.4 hours, and a prolonged mean absorption time of 57 hours. Mean oral bioavailability was 77%. Tissue concentrations ranged from 4 to 140 times the corresponding plasma concentration at 24 and 72 hours after azithromycin administration. CONCLUSIONS AND CLINICAL RELEVANCE: Azithromycin is well absorbed and tolerated by ball pythons. On the basis of plasma pharmacokinetics and tissue concentration data, we suggest an azithromycin dosage in ball pythons of 10 mg/kg, orally, every 2 to 7 days, depending upon the site of infection and susceptibil ity of the infective organism.     

Pharmacokinetics of a single dose of enrofloxacin administered orally to captive Asian elephants (Elephas maximus)

OBJECTIVE: To determine the pharmacokinetics of enrofloxacin after oral administration to captive elephants. ANIMALS: 6 clinically normal adult Asian elephants (Elephas maximus). PROCEDURE: Each elephant received a single dose of enrofloxacin (2.5 mg/kg, PO). Three elephants received their complete diet (pellets and grain) within 2 hours after enrofloxacin administration, whereas the other 3 elephants received only hay within 6 hours after enrofloxacin administration. Serum concentrations of enrofloxacin and ciprofloxacin were measured by use of high-performance liquid chromatography. RESULTS: Harmonic mean half-life after oral administration was 18.4 hours for all elephants. Mean +/- SD peak serum concentration of enrofloxacin was 1.31 +/- 0.40 microg/mL at 5.0 +/- 4.2 hours after administration. Mean area under the curve was 20.72 +/- 4.25 (microg x h)/mL. CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of enrofloxacin to Asian elephants has a prolonged elimination half-life, compared with the elimination half-life for adult horses. In addition, potentially therapeutic concentrations in elephants were obtained when enrofloxacin was administered orally at a dosage of 2.5 mg/kg. Analysis of these results suggests that enrofloxacin administered with feed in the manner described in this study could be a potentially useful antimicrobial for use in treatment of captive Asian elephants with infections attributable to organisms, such as Bordetella spp, Escherichia coli, Mycoplasma spp, Pasteurella spp, Haemophilus spp, Salmonella spp, and Staphylococcus spp.     

Population pharmacokinetics of isoniazid in the treatment of Mycobacterium tuberculosis among Asian and African elephants (Elephas maximus and Loxodonta africana)

We recently described the clinical presentation and treatment of 18 elephants from six herds infected with TB. Treatment protocols and methods varied between herds to include both oral and rectal dosing using multiple drug doses and formulations. In this paper we present information regarding the pharmacokinetics (PK) of isoniazid (INH) in elephants and provide suggestions regarding initial treatment regimens. Forty-one elephants received INH daily by either oral or rectal administration with different formulations. Population PK analysis was performed using Non-linear Mixed Effect Modeling (NONMEM). Results of oral administration indicated that compared with premixed INH solution, the drug exposure was highest with a suspension prepared freshly with INH powder. When INH was concomitantly given as an admixture over food, Tmax was delayed and variability in drug absorption was significantly increased. Compared with oral administration, similar drug exposures were found when INH was dosed rectally. The data generated suggest that a starting dose of 7.5 mg/kg of INH is appropriate for initial TB treatment in elephants when premixed solution is administered directly into the oropharynx or rectal vault and 4 mg/kg are when INH is administered following immediate suspension from powdered form.     

Population pharmacokinetics of pyrazinamide in elephants

This study was undertaken to characterize the population pharmacokinetics (PK), therapeutic dose, and preferred route of administration for pyrazinamide (PZA) in elephants. Twenty-three African (Loxodonta africana) and Asian (Elephas maximus) elephants infected with or in contact with others culture positive for Mycobacterium tuberculosis were dosed under treatment conditions. PZA was dosed daily at 20-30 mg/kg via oral (fasting or nonfasting state) or rectal (enema or suppository) administration. Blood samples were collected 0-24 h postdose. Population PK was estimated using nonlinear mixed effect modeling. Drug absorption was rapid with T(max) at or before 2 h regardless of the method of drug administration. C(max) at a mean dose of 25.6 (+/-4.6) mg/kg was 19.6 (+/-9.5 microg/mL) for PZA given orally under fasting conditions. Under nonfasting conditions at a mean dose of 26.1 +/- 4.2 mg/kg, C(max) was 25% (4.87 +/- 4.89 microg/mL) and area under concentration curve (AUC) was 30% of the values observed under fasting conditions. Mean rectal dose of 32.6 +/- 15.2 mg/kg yielded C(max) of 12.3 +/- 6.3 microg/mL, but comparable AUC to PZA administered orally while fasting. Both oral and rectal administration of PZA appeared to be acceptable and oral dosing is preferred because of the higher C(max) and lower inter-subject variability. A starting dose of 30 mg/kg is recommended with drug monitoring between 1 and 2 h postdose. Higher doses may be required if the achieved C(max) values are below the recommended 20-50 microg/mL range.     

Anatomic and radiographic study of the lacrimal apparatus of llamas.

The anatomy of the nasolacrimal duct of llamas was examined grossly and radiographically in 2 llamas. Dacryocystorhinography was performed on cadaver heads, using a radiographic aqueous contrast agent. Anatomic casts of the nasolacrimal apparatus were obtained by cannulation of the duct and use of polyurethane cast material. Dacryocystorhinography accurately revealed the nasolacrimal apparatus and compared favorably with gross dissections and polyurethane casts.     

ULTRASOUND IMAGING OF THE COELOMIC STRUCTURES IN THE BOA CONSTRICTOR (BOA CONSTRICTOR)

Transverse ultrasound images from three live boa constrictors ( Boa constrictor ) were compared to the corresponding gross sections of a euthanized boa constrictor. The snakes were anesthetized, placed into dorsal recumbency, and imaged through the ventral scutes. Ultrasound images were produced with a real time, B-mode scanner and a linear 7.5-MHz transducer. The heart, liver, stomach, gall bladder, pancreas, kidneys, and fat body were the coelomic structures most consistently recognized ultrasonographically. Results of this study indicate that ultrasound is a useful imaging technique in snakes.     

PNEUMOCOELOM ASSOCIATED WITH SERRATOSPICULUM AMACULATA IN A BALD EAGLE

Serratospiculum amaculata Nemutodes were identified radiographically in the air sacs of an eagle which developed acute respiratory distress several days after treatment for severe head trauma. The nematodes were found at necropsy within the air sacs and lungs. One of the nematodes was found protruding through a hole in the lung. Although this parasite was reported in a falcon which died post operatively this is the first report of death in an eagle related to the presence of this parasite and is also the first time the parasite itself has been observed in a raptor antemortem.