Zoologic medicine practitioners take approved agents (veterinary or human) and extrapolate their use to nonapproved species. The decision on dose, duration, and interval is often made with limited species-specific pharmacokinetic information. Because of the monetary value of these animals or their status as endangered species, this method of "trial and error" for therapeutic dosage selection is inappropriate. In zoologic medicine, various methods have been used in an attempt to extrapolate or predict safe and effective dosage regimens. The simplest and typical method of extrapolating a dosage to a nondomestic species is to use a mg/kg dose established for another domestic species or humans. However, this calculation results in a linear increase in the amount of drug administered as body weight increases. Although common, this method tends to overdose large animals and underdose small animals. The second method is similar, except that it takes the approved dose in a specific species and makes an additional assumption that links the dosage to a physiologic function or anatomic feature. Examples are the use of basal metabolic rate or body-surface area as the basis for dosage extrapolation. Allometric scaling of pharmacokinetic parameters is the final method of dosage extrapolation between species. This is commonly used in the pharmaceutical industry to establish the first dosage in human drug investigations. Adaptation of this method for zoologic medicine may enhance our ability to estimate therapeutic dosages for nondomestic species. This review discusses and compares these three methods for dosage selection and provides examples of extrapolation from the literature.

Abstract. Acute phase protein (APP) immunoassays and serum protein electrophoresis (SPEP) are assays for evaluating the inflammatory response and have use as diagnostic tools in a variety of species. Acute phase proteins are markers of inflammation that are highly conserved across different species while SPEP separates and quantifies serum protein fractions based on their physical properties. In the current study, serum samples from 35 clinically healthy Asian elephants (Elephas maximus) were analyzed using automated assays for C-reactive protein, serum amyloid A, and haptoglobin and SPEP. Robust methods were used to generate reference intervals for the APPs: C-reactive protein (1.3-12.8 mg/l), serum amyloid A (0-47.5 mg/l), and haptoglobin (0-1.10 mg/ml). In addition, SPEP was performed on these samples to establish reference intervals for each protein fraction. A combination of APPs and SPEP measurements are valuable adjunctive diagnostic tools in elephant health care.Key words: Acute phase protein; acute phase response; Asian elephants; Elephas maximus; serum amyloid A; serum protein electrophoresis.Acute phase proteins in Asian elephants 617 inflammatory disease. 8,14 Acute phase proteins are impressively conserved among different species, and reagents made for human APPs have been demonstrated to be cross-reactive in many animal species. 1,2,[4][5][6][7][8][9]14,15,[17][18][19]26 Validation of these reagents has been based on standard methods in clinical pathology (coefficient of variation, linearity under dilution, and recovery analyses) and examination of samples from clinically abnormal animals with known inflammatory processes. 1,2,4,5,7,8,14,18,26 In captive nondomestic species, concurrent measurement of APPs and SPEP fractions are noninvasive assays that can supplement and extend the baseline information obtained from the complete blood cell count, fibrinogen, and standard serum chemistry panels.The objective of the current study was to provide preliminary reference intervals for both APP and SPEP fractions from healthy, captive, Asian elephants housed in North America. A secondary objective was to compare APPs and SPEP protein measurements and determine their potential clinical value from an opportunistic sampling of Asian elephants, categorized either as having observable clinical problems or as clinically healthy.Serum samples were obtained from 35 healthy Asian elephants (group A) ranging in age from 3 to 66 years. Within group A, there were 6 intact males, 1 castrated male, and 28 females. The clinical health of the animals was verified by a review of the medical history and visual physical examination. Elephants were kept in an indoor-outdoor enclosure during daylight hours at a private facility in central Florida. The animals were fed ad libitum grass and orchard hay, various browse species, supplemental bread, fresh fruit, and elephant supplement d-alpha-tocopherol polyethylene glycol 1,000 succinate (TPGS), a a form of vitamin E. Using standard phlebotomy techniques, approximately 6-9 ml of v...

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