Pharmacokinetics of ceftiofur sodium after intramuscular or subcutaneous administration in green iguanas (Iguana iguana)

OBJECTIVE: To determine the pharmacokinetics of ceftiofur sodium after IM and SC administration in green iguanas. ANIMALS: 6 male and 4 female adult green iguanas. PROCEDURE: In a crossover design, 5 iguanas received a single dose of ceftiofur sodium (5 mg/kg) IM, and 5 iguanas received the same dose SC. Blood samples were taken at 0, 20, and 40 minutes and 1, 2, 4, 8, 24, 48, and 72 hours after administration. After a 10-week washout period, each iguana was given the same dose via the reciprocal administration route, and blood was collected in the same fashion. Ceftiofur free-acid equivalents were measured via high-performance liquid chromatography. RESULTS: The first phase intercepts were significantly different between the 2 administration routes. Mean maximum plasma concentration was significantly higher with the IM (28.6 +/- 8.0 microg/mL) than the SC (18.6 +/- 8.3 microg/mL) administration route. There were no significant differences between terminal half-lives (harmonic mean via IM route, 15.7 +/- 4.7 hours; harmonic mean via SC route, 19.7 +/- 6.7 hours) and mean areas under the curve measured to the last time point (IM route, 11,722 +/- 7,907 microg x h/mL; SC route, 12,143 +/- 9,633 microg x h/mL). Ceftiofur free-acid equivalent concentrations were maintained > or = 2 microg/mL for > 24 hours via both routes. CONCLUSIONS AND CLINICAL RELEVANCE: A suggested dosing schedule for ceftiofur sodium in green iguanas for microbes susceptible at > 2 microg/mL would be 5 mg/kg, IM or SC, every 24 hours.     

Pharmacokinetics of inhaled anesthetics in green iguanas (Iguana iguana)

OBJECTIVE: To test the hypothesis that differences in anesthetic uptake and elimination in iguanas would counter the pharmacokinetic effects of blood:gas solubility and thus serve to minimize kinetic differences among inhaled agents. ANIMALS: 6 green iguanas (Iguana iguana). PROCEDURES: Iguanas were anesthetized with isoflurane, sevoflurane, or desflurane in a Latin-square design. Intervals from initial administration of an anesthetic agent to specific induction events and from cessation of administration of an anesthetic agent to specific recovery events were recorded. End-expired gas concentrations were measured during anesthetic washout. RESULTS: Significant differences were not detected for any induction or recovery events for any inhalation agent in iguanas. Washout curves best fit a 2-compartment model, but slopes for both compartments did not differ significantly among the 3 anesthetics. CONCLUSIONS AND CLINICAL RELEVANCE: Differences in blood:gas solubility for isoflurane, sevoflurane, and desflurane did not significantly influence differences in pharmacokinetics for the inhalation agents in iguanas.     

Alfaxalone anaesthesia in the green iguana (Iguana iguana)

ObjectiveTo characterise the anaesthetic effects of alfaxalone administered intramuscularly (IM) at 10, 20, and 30 mg kg^?1.Study designProspective, randomized cross-over study.AnimalsTen juvenile green iguanas (Iguana iguana) of mean body weight (±SD) 480 ± 134 g.MethodsAlfaxalone was administered IM in the triceps of both thoracic limbs. Times for anaesthetic induction, plateau and recovery periods were recorded. Skeletal muscle tone of the jaw, neck, thoracic limbs, pelvic limbs, and tail was scored. The palpebral, corneal and righting reflexes, and the response to painful stimuli were also assessed. Pulse rate and respiratory rate were recorded. Comparisons between different dosages and over time were made using anova.ResultsTimes are given for 10, 20 and 30 mg kg^?1 dosages respectively: mean time to maximal effect was 7.7 ± 2.2, 5.4 ± 1.7 and 3.9 ± 1.2 minutes; duration of the plateau phase was 11.3 ± 3.8, 22.1 ± 6.5 and 39.1 ± 11.5 minutes; recovery time was 10 ± 2.4, 17.5 ± 8.6 and 25 ± 7.1 minutes; and total anaesthetic duration was 29 ± 35.7, 45 ± 8.2 and 68 ± 9.8 minutes. Endotracheal intubation was possible in 40% of the subjects given 10 mg kg^?1 and in 100% subjects given both 20 and 30 mg kg^?1. Loss of response to a painful stimulus was seen in 0/10, 8/10 and 9/10 animals at 10, 20, and 30 mg kg^?1 respectively. There was an initial dose-dependent depression of respiration followed by a significant increase in frequency over time. In contrast, pulse rates decreased by 20% over the duration of the anaesthetic events.Conclusions and clinical relevanceIntramuscular administration of alfaxalone is a simple, rapid and reliable means of achieving relatively brief sedation or anaesthesia in healthy green iguanas. A dosage of 10 mg kg^?1 provides light sedation, appropriate for examination and venipuncture; 20 mg kg^?1 provides a level suitable for minor procedures or for endotracheal intubation and supplementation with inhalational anaesthesia; 30 mg kg^?1 produces an anaesthetic plane suitable for surgical procedures of limited duration (up to 40 minutes).     

Cutaneous melanophoroma in a green iguana (Iguana iguana)

An adult, male, green iguana (Iguana iguana) of unknown age was presented with a history of an enlarging, dark, skin mass in the right axillary region. The mass was excised because neoplasia was suspected. Impression smears of the cut surface of the mass were prepared for cytologic examination, and the mass was fixed for histologic examination. The impression smears contained numerous, discrete, pigmented, neoplastic cells consistent with melanin-producing neoplastic chromatophores. Histologic findings were consistent with a cutaneous melanophoroma. By transmission electron microscopy, the intracytoplasmic pigment granules corresponded to numerous melanosomes and lower numbers of premelanosomes. Tissue sections of the tumor were immunoreactive for Melan A antigen and were negative for S-100 antigen. The cytologic, histologic, electron microscopic, and immunohistochemical findings of the neoplasm were consistent with those of melanophoroma, an uncommon neoplasm of reptiles. The present report augments the limited body of knowledge on cytomorphologic and immunohistochemical characteristics of pigmented neoplasms in reptiles.     

Investigations on blood coagulation in the green iguana (Iguana iguana)

The prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time, kaolin clotting time (KCT), dilute Russell's viper venom time (DRVVT) and reptilase time, as well as five different plasma fibrinogen assays [gravimetry, Jacobsson method (extinction at 280 nm), Millar method (heat precipitation), kinetic turbidometry, Clauss method] and resonance thrombography were performed in 26 clinically healthy green iguanas. All assays were carried out in comparison with pooled normal canine plasma. In iguana plasma, the PT [median (x0.50) = 453-831 s, dependent on the reagent], APTT (x0.50 = 170-242 s, dependent on the reagent), thrombin time (x0.50 = 118 - > 1000 s, dependent on thrombin activity), KCT (x0.50 = 274 s), DRVVT (x0.50 = 349 s) and reptilase time (all samples > 1000 s) were widely scattered at the limit of measurability. Only fibrinogen concentrations measured using the Jacobsson method (x0.50 = 4.40 g/l) correlated well (r = 0.91) with gravimetry (x0.50 = 4.22 g/l). The results of this study indicate a limited suitability and a confined diagnostic significance of the selected methods in the green iguana. This may be caused by the species specificity of certain components of the reagents used, as well as a less optimal test system, i.e. relationship of test reagent to clotting factor concentrations in iguana plasma.     

Diagnosis and management of lymphoma in a green iguana (Iguana iguana)

CASE DESCRIPTION-A 2-year-old female green iguana was examined for anorexia and swelling and pain on palpation in the cranial cervical area. CLINICAL FINDINGS-Marked soft tissue swelling in the cranial cervical area with corresponding cystic swellings in the pharynx were noted. The iguana was considered to be 50% under the expected body weight, given diet and husbandry conditions. The WBC count was markedly elevated, characterized by heterophilia and lymphocytosis. Surgical exploration of the cranial cervical area and histologic and microbial testing identified lymphoma with secondary infection as the cause of the swelling. TREATMENT AND OUTCOME-The tumor was initially treated with a single 10-Gy fraction of radiation directed at the masses in the neck. A vascular access port was placed in the ventral abdominal vein, and a canine chemotherapy protocol was modified for use in the iguana. During the course of treatment, the protocol was modified twice. At 1,008 days from the initiation of treatment, the iguana appeared to be in remission. CLINICAL RELEVANCE-To our knowledge, this is the first reported use of radiation with doxorubicin, vincristine, cyclophosphamide, and prednisone to successfully manage lymphoma in a reptile. A vascular access port was used effectively for drug administration for an extended period. The doxorubicin, vincristine, cyclophosphamide, and prednisone protocol appeared to be safe and effective in this iguana for the management of lymphoma.     

Cytopathic herpesvirus infection in a green iguana (Iguana iguana).

A juvenile male green iguana (Iguana iguana) died 5 days following movement to a room 3-5 degrees C cooler than its previous housing. Gross necropsy lesions were limited to thin body condition. Histologically the animal had multifocal, random, moderate to severe, acute hepatocellular necrosis with intranuclear inclusion bodies at the periphery of the necrotic areas. Electron microscopy of the liver revealed icosahedral viral particles approximately 110 nm in diameter, consistent with a herpesvirus infection. Characteristics of the herpesvirus are similar to those described for iguanid herpesvirus 1.     

Pharmacokinetics of ceftazidime in loggerhead sea turtles (Caretta caretta) after single intravenous and intramuscular injections.

The pharmacokinetics of ceftazidime in yearling loggerhead sea turtles (Caretta caretta) following single i.m and i.v. injections were studied. Eight juvenile 1.25+/-0.18 kg turtles were divided into two groups. Four animals received 20 mg/kg of ceftazidime i.v. and four received the same dose i.m. Plasma ceftazidime concentrations were analyzed by reverse-phase high-performance liquid chromatography. The i.v. and i.m. administration half-lives were 20.59+/-3.24 hr and 19.08+/-0.77 hr, respectively. The volume of distribution was 0.42+/-0.07 L/kg, and the systemic clearance was 0.217+/-0.005 ml/min/kg. Ceftazidime was detected in all blood samples and its concentration exceeded the minimum inhibitory concentration for Pseudomonas for 60 hr after i.m. and i.v. injections.     

Pharmacokinetics of ticarcillin in the loggerhead sea turtle (Caretta caretta) after single intravenous and intramuscular injections.

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.     

Pharmacokinetics of florfenicol in loggerhead sea turtles (Caretta caretta) after single intravenous and intramuscular injections.

The pharmocodynamics of single injections of florfenicol in yearling loggerhead sea turtles (Caretta caretta) were determined. Eight juvenile loggerhead sea turtles weighing 1.25 (+/- 0.18) kg were divided into two groups. Four animals received 30 mg/kg of florfenicol i.v., and four received the same dose i.m. Plasma florfenicol concentrations were analyzed by reverse-phase high performance liquid chromatography. After the i.v. dose, there was a biphasic decline in plasma florfenicol concentration. The initial steep phase from 3 min to 1 hr had a half-life of 3 min, and there was a longer slow phase of elimination, with a half-life that ranged from 2 to 7.8 hr among turtles. The volume of distribution varied greatly and ranged from 10.46 to -60 L/kg. Clearance after the i.v. dose was 3.6-6.3 L/kg/hr. After the i.m. injection, there was a peak within 30 min of 1.4-5.6 microg/ml, and florfenicol was thereafter eliminated with a half-life of 3.2-4.3 hr. With either route, florfenicol plasma concentrations were below the minimum inhibitory concentrations for sensitive bacteria within 1 hr. Florfenicol does not appear to be a practical antibiotic in sea turtles when administered at these doses.     

Pharmacokinetics of oxytetracycline in loggerhead sea turtles (Caretta caretta) after single intravenous and intramuscular injections.

The pharmacokinetics of oxytetracycline in 2-yr-old loggerhead sea turtles (Caretta caretta) after single i.v. and i.m. injections were studied for biologic marking and therapeutic applications. Twenty juvenile turtles were divided into two treatment groups. Ten animals received 25 mg/kg of oxytetracycline i.v. and 10 received the same dosage i.m. Plasma oxytetracycline concentrations were analyzed by reverse-phase high-performance liquid chromatography. Data from the i.v. route best fit a three-compartment model, whereas noncompartmental analysis was used to compare data from both the i.v. and i.m routes. For the i.v. route, means for maximum plasma concentration, terminal phase half-life, systemic clearance, and apparent volume of distribution at steady state were 6.6 microg/ml, 66.1 hr, 290.7 ml/hr/kg, and 18.4 L, respectively. For the i.m. route, means for systemic availability, maximum plasma concentration, and elimination half-life were 91.8%, 1.6 microg/ml, and 61.9 hr, respectively. The remarkably high apparent volume of distribution may possibly be associated with a deep compartment of drug disposition such as bone deposition associated with the large skeletal mass of turtles and the fact that these were well-nourished, growing juveniles. Although maximum plasma concentration by i.m. administration was lower than for the i.v. route, the long elimination time indicates that an infrequent dosing interval may be effective for sensitive bacteria.     

Mycoplasmosis in green iguanas (Iguana iguana).

Mycoplasma iguanae was the suspected etiology of spinal disease in feral iguanas (Iguana iguana) from Florida. In an experimental infection study, juvenile iguanas were inoculated with M. iguanae intravenously or by instillation into the nares. Blood samples obtained at intervals postinoculation were all culture negative for mycoplasma. Gross anatomic and histologic findings at necropsy 12 wk postinoculation were unremarkable. Mycoplasmas were cultured in high numbers from the posterior choanae and upper trachea of some inoculated and control iguanas at necropsy. The 16S rDNA gene sequence of these isolates revealed they were all a previously undescribed strain, Mycoplasma insons proposed species nova. M. iguanae. Mycoplasma iguanae was not recovered from the conjunctivae, choanae, trachea, lung, coelomic cavity, blood, heart, liver, spleen, limb joints, brain, or spinal cord of inoculated iguanas, and the iguanas did not seroconvert. We conclude that M. iguanae is unlikely to be an agent of acute disease in iguanas and that M. insons can be considered as normal flora in the respiratory tract of iguanas.     

Pharmacokinetics of enrofloxacin after single intravenous, intramuscular and subcutaneous injections in lactating cows

Five Ayrshire cows were given enrofloxacin (5 mg/kg body weight) intravenously (i.v.), intramuscularly (i.m.) and subcutaneously (s.c). The antimicrobial activity was measured in milk and serum samples using the agar-diffusion technique. High-performance liquid chromatography (HPLC) assay was used to study the extent of metabolism of enrofloxacin to dprofloxacin. Analysis of the serum concentration-time data was based on statistical moment theory. Mean t _1/2β of antimicrobial activity in serum was 1.7, 5.9 and 5.6 h after i.v., i.m. and s.c. administration, respectively. Both i.m. and s.c. routes were associated with a marked flip-flop phenomenon. Based on HPLC analysis of serum samples, the half-lives of enrofloxacin and ciprofloxacin were approximately the same. A marked proportion of enrofloxacin was metabolized to ciprofloxacin. The enrofloxacin fraction bound in vitro to serum proteins was 36–45%. About 0.2% of the total enrofloxacin dose was found in milk during the first 24h and the amount transferred did not depend on the route of administration. Based on the HPLC data, enrofloxacin concentration in milk was parallel to that in serum, while ciprofloxacin was concentrated in milk. After i.v. injection, the peak concentration of enrofloxacin in milk was reached between 0.7 and 1.3 h but occurred much later for ciprofloxacin ( t _max 5–8 h). After i.m. and s.c. administration the concentration-time curves for both enrofloxacin and ciprofloxacin in milk were shallow and there were no obvious peaks.     

Lethal Ozolaimus megatyphlon infection in a green iguana (Iguana iguana rhinolopa).

An imported 2.5-yr-old female green iguana (Iguana iguana rhinolopa) kept in Greece was presented with a history of anorexia and allotriophagy of 1 mo duration. Upon clinical examination, it was cachectic and had severe abdominal distension and fibrous osteodystrophy. Despite treatment, it died a month later. On necropsy, massive accumulations of threadlike nematode parasites were observed in the large intestine, identified as Ozolaimus megatyphlon, a member of the Oxyuridae family of Pharyngodonidae, a usually nonpathogenic intestinal parasite of iguanas. To the authors' knowledge, its presence has not been reported previously in Europe, although one pathogenic infection has been reported previously in Japan. The animal was presumably infected before importation. Although death was attributed to the heavy parasitic overload, the poor diet and terrarium hygiene, and absence of an anthelminthic regime further contributed to the deterioration of the animal's condition. Recognition of this condition, which may be recently introduced or underdiagnosed, may help improve medical and trade standards concerning this species in practice.     

The cardiovascular dose-response effects of isoflurane alone and combined with butorphanol in the green iguana (Iguana iguana)

Objective To assess the cardiovascular effects (arterial blood pressure, heart rate, and metabolic acid–base status) of three doses (MAC multiples) of isoflurane alone and combined with butorphanol in the green iguana (Iguana iguana). Study design Prospective randomized double‐blind, two‐period cross‐over trial. Animals Six mature healthy green iguanas (Iguana iguana). Methods The iguanas received each of two treatments, saline 0.1 mL kg^?1 (SAL) and butorphanol 1.0 mg kg^?1 (BUT) during isoflurane anesthesia. Treatments were separated by at least 1 week. The iguanas were exposed to each of the three minimum alveolar concentration (MAC) multiples (1.0, 1.5, and 2.0) in random order. Anesthesia was induced with isoflurane and maintained using controlled ventilation. Instrumentation included use of an ECG, airway gas monitor, cloacal thermometer, esophageal pulse oximeter, and the placement of a femoral arterial catheter. Body temperature was stabilized and maintained at 32 °C. The treatment was administered, and the animals were equilibrated for 20 minutes at each MAC multiple. At each concentration, the heart rate, blood pressure (systolic, mean, diastolic), end‐tidal CO₂, and SpO₂ were measured. At 1.0 and 2.0 MAC, simultaneous blood samples were drawn from the tail vein/artery complex and femoral catheter for blood gas analysis. Data were analyzed using a two‐way analysis of variance for repeated measures looking for differences between treatments and among MAC multiples. Results There were no significant differences in any of the cardiovascular variables between the treatments. Significant differences among isoflurane MAC multiples were observed for HR, mean, diastolic, and systolic blood pressures. Blood pressure and heart rate decreased with an increasing dose of anesthetic. There were no significant differences between treatments or MAC multiples for any of the blood gas variables. The blood pH, PCO₂, HCO₃^?, and hemoglobin saturation differed significantly between sites. Pulse oximetry values measured from the carotid complex did not correlate with and were significantly different from the calculated hemoglobin saturation values determined using the gas analyzer. Conclusion and clinical relevance Cardiovascular depression associated with isoflurane anesthesia in the green iguana is dose dependent. The degree of cardiovascular depression was not significantly different when isoflurane was combined with butorphanol. This finding suggests that the pre‐emptive or intraoperative use of butorphanol is unlikely to be detrimental to cardiovascular function. Butorphanol may be a useful anesthetic adjunct to isoflurane anesthesia in the green iguana.