The equation MR=aMb is used to express the relationship between metabolic rate (MR) and body weight (M) in animals. The mass constant (a) and mass exponent (b) differ between taxonomic or ecologic groups. Within the broad category of allometric scaling, metabolic scaling relates pharmacokinetic parameters to metabolic rate. Metabolic scaling has been used for both people and animals and has become a fairly common technique in human and veterinary medicine for determination of drug dosages and frequency of administration.2 This technique is used both interspecifically, for species in which no pharmacokinetic information is available for a particular drug, and intraspecifically, for species that exhibit a wide range of body sizes. Metabolic scaling of drug dosages may be applicable to many animal species. Intraspecific metabolic scaling may be a particularly useful tool in reptile medicine as many reptiles show a tremendous variation in size with age, sex, and maturity, with green iguanas experiencing a 600-fold increase in size from a 10-g neonate to a 6000-g adult.
The use of metabolic scaling has become more common in exotic animal practice for which little pharmacokinetic or physiologic data may be available about a particular species.4,5 Data derived from pharmacokinetic studies in one species are used to mathematically determine an appropriate dose and interval of administration for a species in which no pharmacokinetic information is available. This methodology depends upon the metabolic allometric equation of the unknown species approximating that of the known species. Thus, the mass exponent and the mass constant in the equation relating metabolic rate for body mass should be approximately the same for both unknown and known species. If the mass constant and mass exponent in the unknown species fail to approximate that of the known species, then inappropriate dosing will occur. Further, physiologic and biochemical pathways may differ between different species, making metabolic scaling impractical. Allometric scaling may be most accurate when used intraspecifically, with pharmacokinetic information available for that species and adjustments made for size differences.
Allometric scaling of drug dosages in exotic animal medicine is based on the assumption that pharmacokinetic parameters, such as half-life and clearance, scale to body mass to the same power as metabolic rate scales to body mass. In theory, knowledge of the mass constant and exponent of the equation relating metabolic rate and body mass in green iguanas, combined with pharmacokinetic information, should allow the veterinarian to account for size differences in iguanas and formulate an appropriate dose. However, use of this dosing procedure has not been studied in reptiles and may not be more effective than traditional methods in which dosing is directly proportional to body weight and dosing interval is not adjusted to body mass. Scaling based on metabolic rate is often not as effective as is using allometry to scale each pharmacokinetic parameter separately for each individual drug.1,3 Furthermore, the kinetics of some drugs do not seem to lend themselves to prediction by either allometric or metabolic interspecific scaling in mammals.1,3
The objective of this study was to examine the relationship between pharmacokinetic parameters of enrofloxacin (Baytril, Bayer, Leverkusen, Germany) and body size in green iguanas. Enrofloxacin is a broad-spectrum fluoroquinolone antibiotic that is primarily cleared by the kidneys in mammals. Iguanas were maintained at 30°C. (86°F.) for 1 wk prior to and during the study and were fed a commercial iguana food (Zeigler Bros., Gardners, PA, USA). In the preliminary portion of this study, 10 green iguanas, ranging in size from 480–3,824 g, were given injectable enrofloxacin at 5 mg/kg intravenously by jugular catheter. Ten blood samples were taken between time 0 and 96 hr post-administration. The plasma concentrations of both ciprofloxacin and enrofloxacin were measured using liquid chromatography with ultraviolet or mass spectroscopy detectors at either North Carolina State University or University of California at Davis. The plasma concentration vs. time profile curve was analyzed non-compartmentally using Kinetica (InnaPhase, Champs sur Marne, France).
Clearance, half-life, mean residence time (MRT), volume of distribution at steady state (Vdss), and Vdarea were plotted against body mass on a double log plot with linear regression of the resulting curve. Both volume of distribution parameters were significantly correlated with body size with an R2=0.92 and 0.93 for Vdss and Vdarea, respectively, and scaled to body mass with a slope=0.81 and 0.78. Drug half-life, clearance, and MRT were not as strongly correlated to body mass, with R2=0.43, 0.55, and 0.58, and slope=0.38, 0.40, and 0.41.
The standard metabolic rate of green iguanas scales to body mass by approximately the 3/4 power (unpublished data). Preliminary results from this study indicate that metabolic scaling can be used to predict some pharmacokinetic parameters, such as volume of distribution, as both scale to a similar exponent. Metabolic scaling may not be effective in predicting other parameters, such as half-life, clearance, and MRT, as these either do not scale to body size or scale to a different exponent than does metabolic rate. Dose is dependent on volume of distribution, whereas half-life, clearance, and MRT determine the dosing interval. Therefore, although metabolic scaling can be used to adjust the dose of enrofloxacin in various-sized iguanas, its use may not be justified in adjusting the dosing interval to body size.
The University gratefully acknowledges and thanks Morris Animal Foundation for its financial, technical, and administrative assistance in funding and managing the research through which this information was discovered. Without the Foundation’s support and encouragement, this presentation would not be possible. We also thankfully acknowledge support from Bayer Corporation and Pet Care Trust. Additionally, Santa Fe Community College Teaching Zoo graciously provided care for the study animals.
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3. Riviere JE, T Martin-Jimenez, SF Sundlof, AL Craigmill. 1997. Interspecies allometric analysis of the comparative pharmacokinetics of 44 drugs across veterinary and laboratory animal species. J. Vet. Pharmacol. Therap. 20: 453–463.
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5. Sedgwick CJ. 1993. Allometric scaling and emergency care: the importance of body size. In: Fowler ME, ed. Zoo and Wild Animal Medicine. Current Therapy 3. W.B. Saunders Co., Philadelphia, PN, Pp. 34–37.