SERUM VITAMIN D AND SELECTED BIOMARKERS OF CALCIUM HOMEOSTASIS IN ASIAN ELEPHANTS (ELEPHAS MAXIMUS) MANAGED AT A LOW LATITUDE.

An understanding of species-specific vitamin D metabolism and its role in calcium homeostasis is essential for correct diet formulation and development of husbandry protocols for managed nondomestic species. This study documented serum vitamin D metabolites and other analytes involved in calcium homeostasis in Asian elephants (Elephas maximus) managed at a latitude similar to their wild natural habitat. Serum values for 33 elephants managed at a low latitude were measured in the peak of summer, revealing low vitamin D2 (25(OH)D2 2.3 ± 0.6 ng/ ml and 24,25(OH)2D2 2.17 ± 0.52 ng/ml) and nondetectable vitamin D3. Serum minerals (calcium, phosphorus, magnesium), ionized calcium, and parathyroid hormone were within normal reported ranges. In comparison with previously reported values in elephants managed at a high latitude, 25(OH)D2 (P < 0.001), 24,25(OH)2D2 (P = 0.001), and magnesium (P = 0.013) were significantly lower, and parathyroid hormone was significantly higher (P < 0.001). The lack of D3 production during ample sun exposure at a low latitude suggests that Asian elephants are incapable of cutaneous photobiosynthesis of vitamin D, and that low serum D2 is normal for this species.

EVALUATION OF PLASMA CARDIAC TROPONIN I IN ASIAN ELEPHANTS (ELEPHAS MAXIMUS) USING TWO CLINICAL ANALYZERS.

Cardiac troponin I (cTnI) is specific to myocardial tissue, highly conserved across taxa, and a reliable indicator of myocardial disease in human and veterinary medicine. Biomarkers, like cTnI, may be useful for cardiac evaluation of elephants because the application of other modalities is complicated by the size of the animal. The goal of this study was to establish observed ranges for plasma cTnI in Asian elephants (Elephas maximus) measured by two point-of-care analyzers. Blood was collected from captive juvenile (≤15 yr; n = 9), adult (16-50 yr; n = 42), and geriatric (>50 yr; n = 16) elephants. Following centrifugation, heparinized plasma was stored at 5°C prior to and in between analyses on iSTAT (Abbott Point of Care Inc, Princeton, NJ 08540, USA) and HUBI-QUANpro (Humiasis Co, Ltd, Anyang-si 14042, South Korea) analyzers. With the exception of two results, plasma concentrations of cTnI were below the limit of quantification (LOQ < 0.05 ng/ml) for the HUBI-QUANpro (n = 64), which prohibited comparison between the two analyzers. Observed ranges were determined for plasma cTnI concentrations reported by the iSTAT for the entire population sampled (n = 58; mean 0.011 ng/ml; SD ± 0.013 ng/ml; range 0.00-0.07 ng/ml; 95% CI 0.008-0.015 ng/ml; median 0.01 ng/ml) and with outliers excluded (n = 50; mean 0.007 ng/ml; SD ± 0.007 ng/ml; range 0.00-0.02 ng/ml; 95% CI 0.005-0.009 ng/ml; median 0.01 ng/ml). No significant differences were observed between age classes (P = 0.70) or sexes (P = 0.34). Higher cTnI concentrations were significantly correlated with increasing age (Pearson's r = 0.426; P = 0.002). Future studies are warranted to investigate the diagnostic potential of plasma cTnI in Asian elephants.

Ovarian cyclicity and prolactin status of African elephants (Loxodonta africana) in North American zoos may be influenced by life experience and individual temperament.

Hyperprolactinemia is an endocrine disorder associated with infertility in many species, including elephants. In a recent survey of zoos accredited by the Association of Zoos and Aquariums (AZA), over half of African elephant females (N = 101) were not cycling normally, 30% of which exhibited hyperprolactinemia. We examined whether life experience and temperament predict ovarian cyclicity and circulating prolactin status in individual African elephant females. We hypothesized that, similar to humans, acyclicity and hyperprolactinemia in elephants will be associated with an apprehensive or fearful, anxious temperament, and an increased number of potentially challenging life events (transfers, deaths and births). Ninety-five adult African elephant females housed at 37 AZA institutions were included in this study. Blood samples were collected twice a month for 1 year to determine ovarian cycle (cycling, n = 44; irregular, n = 13; non-cycling, n = 38) and prolactin (normal, n = 44; low; n = 23; high; n = 28) status. Keeper ratings on a 6-point scale were obtained on 32 temperament traits in 85 of these elephants. We determined that giving birth and being exposed to herd mates entering the facility were positively associated with normal ovarian cycle and prolactin profiles. By contrast, age, serum cortisol, and an increased number of herd mates leaving a facility were negatively associated with both. Contrary to our hypothesis, hyperprolactinemia was associated with a popular and caring temperament rating, whereas consistently low prolactin was associated with a fearful, apprehensive temperament. These findings indicate that pituitary-ovarian function may be impacted by life history (cyclicity) and temperament (prolactin), which should be taken into consideration when making management decisions.

BIOLOGICAL VARIATION OF HEMATOLOGY AND BIOCHEMISTRY PARAMETERS FOR THE ASIAN ELEPHANT (ELEPHAS MAXIMUS), AND APPLICABILITY OF POPULATION-DERIVED REFERENCE INTERVALS.

The aim of this study was to objectively evaluate the biological variation of healthy Asian elephant (Elephas maximus) hematology and biochemistry parameters, therefore enabling evidence-based clinical decision-making to improve patient management. Ten clinically healthy elephants had blood samples collected weekly for 5 wk under standardized conditions. The analytical, between- and within-individual variation, index of individuality, and reference change values were calculated using previously reported methods. Large between-individual variation and small within-individual variation for almost all parameters indicated that individual normal values should be used for interpreting blood results from Asian elephants.

SEX DIFFERENCES IN THE REFERENCE INTERVALS OF HEALTH PARAMETERS IN SEMICAPTIVE ASIAN ELEPHANTS (ELEPHAS MAXIMUS) FROM MYANMAR.

The reference intervals of health parameters are valuable tools for veterinarians and conservationists to monitor the health status and viability of endangered species. Natural variation in the health of the long-lived Asian elephant (Elephas maximus) is poorly understood, particularly in relation to differences between males and females. Longitudinal health data were collected from clinical examination, hematology, and serum chemistry analyses over 3 yr from 227 healthy individually marked Asian elephants varying in age and sex. The study population was semicaptive and used in Myanmar's timber industry, but maintained natural feeding and breeding behavior. Body condition score (BCS) and blood pressure were investigated in clinical examinations. Hematological parameters included hematocrit, hemoglobin, total white blood cell count, and differential blood cell counts. Serum chemistry parameters included blood urea nitrogen, creatinine, total protein, albumin, globulins, aspartate aminotransferase, alkaline phosphatase, triglycerides, creatine kinase, glucose, calcium, potassium, sodium, and chloride. To the knowledge of the authors, this is the first description of BCS in an elephant population outside of zoos, and of blood pressure in this species using a novel adaptation of the Intelli Wrap Cuff pressure monitor. Several differences between the sexes were observed, with females generally having higher BCS and triglycerides, and males displaying higher alkaline phosphatase and glucose levels. This study provides important clinical tools that can be used to assess the health status and improve management in this endangered species.

Hyperprolactinemic African elephant (Loxodonta africana) females exhibit elevated dopamine, oxytocin and serotonin concentrations compared to normal cycling and noncycling, low prolactin elephants†.

Many zoo elephants do not cycle normally, and for African elephants, it is often associated with hyperprolactinemia. Dopamine agonists successfully treat hyperprolactinemia-induced ovarian dysfunction in women, but not elephants. The objective of this study was to determine how longitudinal dopamine, serotonin, and oxytocin patterns in African elephants are related to ovarian cycle function. We hypothesized that dopamine concentrations are decreased, while oxytocin and serotonin are increased in non-cycling, hyperprolactinemic African elephants. Weekly urine and serum samples were collected for eight consecutive months from 28 female African elephants. Females were categorized as follows: (1) non-cycling with average prolactin concentrations of 15 ng/ml or greater (HIGH; n = 7); (2) non-cycling with average prolactin concentrations below 15 ng/ml (LOW; n = 13); and (3) cycling with normal progestagen and prolactin patterns (CYCLING; n = 8). Both oxytocin and serotonin were elevated in hyperprolactinemic elephants. Thus, we propose that stimulatory factors may play a role in the observed hyperprolactinemia in this species. Interestingly, rather than being reduced as hypothesized, urinary dopamine was elevated in hyperprolactinemic elephants compared to CYCLING and LOW prolactin groups. Despite its apparent lack of regulatory control over prolactin, this new evidence suggests that dopamine synthesis and secretion are not impaired in these elephants, and perhaps are augmented.

Variation in metabolic factors and gonadal, pituitary, thyroid, and adrenal hormones in association with musth in African and Asian elephant bulls.

Longitudinal analyses of serum testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, glucose, insulin, triglycerides, cholesterol, total and free thyroxine (T4), total triiodothyronine (T3), thyroid stimulating hormone (TSH), and cortisol were conducted to investigate pituitary, metabolic, and adrenal changes related to testicular function and musth status in zoo-housed elephant bulls. Blood samples were collected twice a month for 12 months from 14 African and 12 Asian bulls at 17 facilities in North America. Building on previous studies, our results show that musth is associated with increased testosterone, LH, FSH, and cortisol secretion, and a decrease in thyroid hormone (total and free T4) production. In addition, glucose and triglycerides were higher during musth than non-musth periods, indicative of altered sugar and fat metabolism. There were significant differences associated with age for LH, FSH and testosterone, all increasing, whereas the glucose-to-insulin ratio (G:I) decreased with age. A species comparison found African and Asian elephants differed in measures of insulin, prolactin, cholesterol and the G:I. Across all hormones, high inter-individual variability was observed, making it difficult to define a general musth endocrine profile or to assess musth status from single samples. These results highlight the need for facilities hosting bulls to closely and consistently monitor each individual from an early age and throughout musth and non-musth periods to determine the pattern for each male.

USING IN-HOUSE HEMATOLOGY TO DIRECT DECISION-MAKING IN THE SUCCESSFUL TREATMENT AND MONITORING OF A CLINICAL AND SUBSEQUENTLY SUBCLINICAL CASE OF ELEPHANT ENDOTHELIOTROPIC HERPESVIRUS 1B.

A 3.5-yr-old asymptomatic female Asian elephant (Elephas maximus) with a high load of circulating EEHV1B DNA on qPCR on a routine blood sample, showed progressive depletion of monocytes, lymphocytes, and platelets. Twice daily IV ganciclovir, plasma transfusions, and fluid therapy coincided with a decreasing viral load, which may support potential efficacy of this antiviral drug. An increase in lymphocytes followed initial treatment and preceded the onset of clinical signs. Administration of short-acting glucocorticosteroids for two consecutive days preceded a reduction of lymphocytes, recovery and maturation of monocytes, and gradually decreasing clinical signs, illustrating the potential value of glucocorticosteroids in treatment of clinical EEHV. Three subsequent subclinical episodes with high monocyte and platelet counts did not require intervention. Decision-making was led not just by quantification of viral load and clinical signs, but more specifically by interpretation of the hematological changes using easily accessible, in-house blood smear analysis.

THROMBOELASTOGRAPHY IN THE HEALTHY ASIAN ELEPHANT ( ELEPHAS MAXIMUS): REFERENCE INTERVALS AND EFFECTS OF STORAGE.

Hemorrhagic disease associated with elephant endotheliotropic herpesvirus infection is the most-frequent cause of mortality in captive Asian elephants ( Elephas maximus). Survival relies on intensive monitoring of hemostatic status. Thromboelastography (TEG) utilizes whole blood samples containing all the blood components of hemostasis and is therefore a sensitive indicator of the clinical status in the patient. This study was performed to assess the practicability of TEG in Asian elephants in a zoo environment. Citrated stabilized whole blood samples were obtained from 44 healthy Asian elephants. Kaolin-activated TEG was performed on whole blood at 60 min and 24 hr postsampling (to replicate shipment to an external laboratory) as well as on freeze-thawed plasma samples, 12-14 mo postsampling. Reference intervals were calculated for fresh whole blood and freeze-thawed plasma samples. In the 24-hr analysis, storage artifacts, likely due to cellular degeneration, resulted in a hypercoagulable thromboelastogram and thus reduced sensitivity for detecting coagulopathies. Therefore, delayed analysis of whole blood samples is not recommended.

EFFECTS OF GONADOTROPIN-RELEASING HORMONE ANTAGONIST DEGARELIX ON MUSTH AND SERUM TESTOSTERONE CONCENTRATIONS IN ASIAN ELEPHANTS ( ELEPHAS MAXIMUS).

Two male Asian elephants (bulls 1 and 2) in musth were subcutaneously injected with a long-acting gonadotropin-releasing hormone (GnRH) antagonist, degarelix acetate (240 µg/kg; total dose of 960 mg). Musth behavior (MB) and temporal gland secretions (TGS) were monitored and serum testosterone concentrations were determined. In bull 1, MB and TGS ceased on day 1 and reappeared 5.5 mo after the treatment (day 0). During the subsequent musth cycle, MB and TGS ceased on day 1 and did not appear for 4 mo. In bull 2, MB and TGS ceased at day 7 after the treatment. Musth behavior and TGS recurred on Day 11 and continued for 1 wk, then disappeared for 8 mo. Serum testosterone concentrations decreased ( P < 0.05) in all occasions from day 0 (29.8 ± 15.8 ng/ml; mean ± SEM) to day 1 (2.2 ± 1.1 ng/ml), suggesting a sudden drop in circulating testosterone in musth elephants after the GnRH-antagonist treatment.

Blood species discrimination using proton nuclear magnetic resonance spectroscopy.

Blood species identification is an important challenge in forensic science. Conventional methods used for blood species analysis are destructive and associated with time-consuming sample preparation steps. Nuclear magnetic resonance (NMR) spectroscopy is known for its nondestructive properties and fast results. This research study presents a proton (1H) NMR method to discriminate blood species including human, cat, dog, elephant, and bison. Characteristic signals acting as markers are observed for each species. Moreover, the data are evaluated by principle component analysis (PCA) and support vector machines (SVM). A 100% correct species recognition between human and nonhuman species is achieved using radial basis kernel function (RBF) and standardized data. The research study shows that 1H NMR spectroscopy is a powerful tool for differentiating human and nonhuman blood showing a great significance to forensic science.

EVALUATION OF THE I-STAT PORTABLE CLINICAL ANALYZER FOR MEASUREMENT OF IONIZED CALCIUM AND SELECTED BLOOD CHEMISTRY VALUES IN ASIAN ELEPHANTS (ELEPHAS MAXIMUS).

Thei-STAT® portable clinical analyzer (PCA) provides patient-side results for hematologic, biochemical, and blood gas values when immediate results are desired. This analyzer is commonly used in nondomestic animals; however, validation of this method in comparison with traditional benchtop methods should be performed for each species. In this study, the i-STAT PCA was compared with the Radiometer ABL 800 Flex benchtop analyzer using 24 heparinized whole blood samples obtained from healthy E. maximus . In addition, the effect of sample storage was evaluated on the i-STAT PCA. Analytes evaluated were hydrogen ion concentration (pH), glucose, potassium (K+), sodium (Na+), bicarbonate (HCO3-), total carbon dioxide (TCO2), partial pressure of carbon dioxide (PCO2), and ionized calcium (iCa2+). Statistical analysis using correlation coefficients, Passing-Bablok regression analysis, and Bland-Altman plots found good agreement between results from samples run immediately after phlebotomy and 4 hr postsampling on the i-STAT PCA with the exception of K+, which is known to change with sample storage. Comparison of the results from the two analyzers at 4 hr postsampling found very strong or strong correlation in all values except K+, with statistically significant bias in all values except glucose and PCO2. Despite bias, mean differences assessed via Bland-Altman plots were clinically acceptable for all analytes excluding K+. Within the reference range for iCa2+, the iCa2+ values obtained by the i-STAT PCA and Radiometer ABL 800 Flex were close in value, however in light of the constant and proportionate biases detected, overestimation at higher values and underestimation at lower values of iCa2+ by the i-STAT PCA would be of potential concern. This study supports the use of the i-STAT PCA for the evaluation of these analytes, with the exception of K+, in the Asian elephant.

ASSESSMENT OF A LANCET-AND-SWAB BLOOD SAMPLING TECHNIQUE FOR SURVEILLANCE OF ELEPHANT ENDOTHELIOTROPIC HERPESVIRUS INFECTION.

Lancing a finger elicits minimal pain in humans and is applied routinely to obtain small volumes of blood for clinical diagnostics. A modified lancet bleeding method and several blood sampling matrices were evaluated in this study for the purpose of routine elephant endotheliotropic herpesvirus (EEHV) surveillance in Asian elephants (Elephas maximus). The procedure enabled weekly sampling from elephants as young as 9 mo of age. The blood sampling matrices were evaluated for their sensitivity measuring ß-actin, tumor necrosis factor α, and/or EEHV-1 by quantitative polymerase chain reaction assays. Foam and flocked swabs produced significantly (P < 0.05) lower quantitation cycles, ie, increased analytical sensitivity, than filter papers, Whatman® FTA cards, or conventional cotton-tipped swabs. The two swab types also demonstrated comparable analytical sensitivity to that of a similar volume of EDTA whole blood for the detection of EEHV-1 DNA. This lancet-and-swab technique proved satisfactory for the detection of EEHV-1 viremia in two Asian elephant calves, and in one instance viremia could be detected 5 days prior to the development of clinical signs. Low blood yield from the lancet application may reduce sensitivity and compromise early detection of viremia. Therefore, standard venipuncture remains the recommended blood sampling method, and training for consistent and regular vein access should continue to be the priority for collections holding elephants. However, if appropriate measures are taken to collect an optimum blood volume, this lancet-and-swab technique offers a suitable alternative for EEHV surveillance in situations where venipuncture may not be practical.

Ovarian acyclicity in zoo African elephants (Loxodonta africana) is associated with high body condition scores and elevated serum insulin and leptin.

The purpose of the present study was to determine whether excessive body fat and altered metabolic hormone concentrations in the circulation were associated with ovarian acyclicity in the world's largest land mammal, the African elephant. We compared body condition, glucose, insulin and leptin concentrations and the glucose-to-insulin ratio (G:I) between cycling (n=23; normal 14-16 week cycles based on serum progestagens for at least 2 years) and non-cycling (n=23; consistent baseline progestagen concentrations for at least 2 years) females. A validated body condition score (BCS) index (five-point scale; 1=thinnest, 5=fattest) was used to assess the degree of fatness of the study elephants. The mean BCS of non-cycling elephants was higher than that of their cycling counterparts. There were differences in concentrations of serum metabolic biomarkers, with non-cycling elephants in the BCS 5 category having higher leptin and insulin concentrations and a lower G:I ratio than cycling BCS 5 females. Using 'non-cycling' as the outcome variable in regression models, high BCS was a strong predictor of a non-cycling status. This study provides the first evidence that ovarian acyclicity in zoo African elephants is associated with body condition indicative of obesity, as well as elevated, perturbed biomarkers of metabolic status.

Pharmacokinetics of amoxicillin trihydrate in male Asian elephants (Elephas maximus) following intramuscular administration.

The purpose of this study was to investigate the pharmacokinetic characteristics of amoxicillin (AMX) trihydrate in male Asian elephants, Elephas maximus, following intramuscular administration at two dosages of 5.5 and 11 mg/kg body weight (b.w.). Blood samples were collected from 0.5 up to 72 h. The concentration of AMX in elephant plasma was measured using liquid chromatography electrospray ionization mass spectrometry. AMX was measurable up to 24 h after administration at two dosages. Peak plasma concentration (Cmax ) was 1.20 ± 0.39 µg/mL after i.m. administration at a dosage of 5.5 mg/kg b.w., whereas it was 3.40 ± 0.63 µg/mL at a dosage of 11 mg/kg b.w. A noncompartment model was developed to describe the disposition of AMX in Asian elephants. Based on the preliminary findings found in this research, the dosage of 5.5 and 11 mg/kg b.w. produced drug plasma concentrations higher than 0.25 mg/mL for 24 h after i.m. administration. Thereafter, i.m. administration with AMX at a dosage of 5.5 mg/kg b.w. appeared a more suitable dose than 11 mg/kg b.w. However, more studies are needed to determine AMX clinical effectiveness in elephants.

PHARMACOKINETICS OF A SINGLE DOSE OF METRONIDAZOLE AFTER RECTAL ADMINISTRATION IN CAPTIVE ASIAN ELEPHANTS (ELEPHAS MAXIMUS).

Metronidazole is a nitroimidazole antibacterial and antiprotozoal drug with bacteriocidal activity against a broad range of anaerobic bacteria. It is a recognized treatment for elephants diagnosed with anaerobic bacterial infection or protozoal disease or exhibiting signs of colonic impaction, diarrhea, and colic. This study evaluated the pharmacokinetics of rectally administered metronidazole (15 mg/kg) in five adult female Asian elephants (Elephas maximus). Serum samples were collected from each animal for 96 hr after rectal administration of metronidazole. Serum concentrations of metronidazole and its primary metabolite, hydroxymetronidazole, were measured via ultraperformance liquid chromatography. Data were analyzed via a noncompartmental pharmacokinetic approach. Results indicated that serum levels of metronidazole were quantifiable at the 0.25 hr time point and absent in all elephants by the 96 hr time point. The serum peak concentration (mean ± SD, 13.15 ± 2.59 µg/ml) and area under the curve from time 0 to infinity (mean ± SD, 108.79 ± 24.77 hr × µg/ml) were higher than that reported in domestic horses after similar usage. Concurrently, the time of maximum serum concentration (mean ± SD, 1.2 ± 0.45 hr) and terminal elimination half-life (harmonic mean ± pseudo-SD, 7.85 ± 0.93 hr) were longer when compared to equine reports. Rectal administration of metronidazole was well tolerated and rapidly absorbed in all study elephants. Based on the findings in this study, metronidazole administered at a single dose of 15 mg/kg per rectum in the Asian elephant is likely to result in serum concentrations above 4 µg/ml for 8 hr and above 2 µg/ml for 24 hr after treatment is administered. Dosing recommendations should reflect the mean inhibitory concentration of metronidazole for each pathogen.

EFFECT OF ε-AMINOCAPROIC ACID ON FIBRINOLYSIS IN PLASMA OF ASIAN ELEPHANTS (ELEPHAS MAXIMUS).

ε-Aminocaproic acid (EACA) is a lysine analogue antifibrinolytic drug used to treat bleeding disorders in humans and domestic animals. Use in zoological medicine is rare and dose recommendations are anecdotal, but EACA may be a valuable therapeutic option for bleeding disorders in exotic species, including Asian elephants ( Elephas maximus ). This study used an in vitro model of hyperfibrinolysis and a thromboelastograph-based assay to estimate the therapeutic plasma concentration of EACA in Asian elephants (61.5 µg/ml, 95% CI = 34.6-88.5 µg/ml). Substantial but incomplete inhibition of lysis was seen at relatively low concentrations of EACA (40 µg/ml). Asian elephants appear sensitive to EACA-mediated inhibition of hyperfibrinolysis. Doses published for domestic animals, targeting higher plasma concentrations, may be inappropriate in this species.

ISONIAZID AND RIFAMPIN PHARMACOKINETICS IN TWO ASIAN ELEPHANTS (ELEPHAS MAXIMUS) INFECTED WITH MYCOBACTERIUM TUBERCULOSIS.

This report describes the pharmacokinetic profiles of chronically administered oral isoniazid and rifampin in one adult male and one adult female Asian elephant ( Elephas maximus ) that were asymptomatically infected with Mycobacterium tuberculosis . Rifampin's half-life was reduced when compared to previous single-dose pharmacokinetic profiles of healthy uninfected Asian elephants. Both elephants experienced delayed absorption of isoniazid and rifampin as compared to previous pharmacokinetic studies in this species. The altered pharmacokinetics of both drugs in repeated-dosing clinical situations underscores the need for individual therapeutic drug monitoring for tuberculosis treatment.

Population pharmacokinetics of rifampin in the treatment of Mycobacterium tuberculosis in Asian elephants.

The objective of this study was to develop a population pharmacokinetic model for rifampin in elephants. Rifampin concentration data from three sources were pooled to provide a total of 233 oral concentrations from 37 Asian elephants. The population pharmacokinetic models were created using Monolix (version 4.2). Simulations were conducted using ModelRisk. We examined the influence of age, food, sex, and weight as model covariates. We further optimized the dosing of rifampin based upon simulations using the population pharmacokinetic model. Rifampin pharmacokinetics were best described by a one-compartment open model including first-order absorption with a lag time and first-order elimination. Body weight was a significant covariate for volume of distribution, and food intake was a significant covariate for lag time. The median Cmax of 6.07 µg/mL was below the target range of 8-24 µg/mL. Monte Carlo simulations predicted the highest treatable MIC of 0.25 µg/mL with the current initial dosing recommendation of 10 mg/kg, based upon a previously published target AUC0-24/MIC > 271 (fAUC > 41). Simulations from the population model indicate that the current dose of 10 mg/kg may be adequate for MICs up to 0.25 µg/mL. While the targeted AUC/MIC may be adequate for most MICs, the median Cmax for all elephants is below the human and elephant targeted ranges.

Effect of feeding different levels of wheat roti on nutrient utilization and blood metabolite profile in semi-captive Asian elephants (Elephas maximus).

This experiment was conducted to study the effect of different levels of wheat roti (WR) on nutrient utilization and blood metabolites in Asian elephants fed roughages ad libitum. Nine (3 M, 6 F) Asian elephants (14-52 years of age, 1909-3968 kg BW) were used in an experiment based on replicated Latin square design. Animals in each group (n = 3) were assigned to one of the three dietary treatments in a manner that animals in all the three groups were exposed to all the three treatments in three different periods. Each feeding trial comprised 30 days (25 days of adaptation and 5 days collection period). The amount of WR fed to the elephants was 0.18, 0.12 and 0.06% of BW in groups I, II and III, respectively. They were allowed to forage in the nearby forests for 6 h/day and to bathe for 2 h/day. The animals had ad libitum access to cut Rohini (Mallotus philippensis) trees in their night shelter. Intake and apparent digestibility of dry matter (DM), crude protein (CP), gross energy (GE), Ca, P, Fe, Cu and Zn were measured. Feed consumption was not significantly different among the groups. Significant (p < 0.01) decrease in digestibility of DM and GE and blood glucose concentration was observed with decreased level of WR in the diet. Feeding of WR at 0.06% of BW supplied adequate amount of DE, CP, Ca, P, Fe, Cu and Zn to meet requirement for adult maintenance. Feeding of WR in excess of 0.06% of BW supplied DE in excess of requirement, increased blood glucose concentration which may cause obesity and other associated health problems. It was concluded that the amount of WR should be restricted to 0.06% of BW in the diet of captive Asian elephants.