ABSTRACT

Drug-elimination times for 13 drugs were extracted from published reports of drug-studies in four species of ranid frogs and compared to elimination-times in man, rat and mouse. The frogs had been studied under conditions that minimized drug loss by transcutaneous diffusion. Frog/mammal ratios for elimination-times were compared to expectations based on scaling to the inverse of their relative metabolic rates or to allometric scaling adjusted for differences between taxa. Estimates based on either scaling procedure were similar. Nine of the 13 drugs were studied in the bullfrog, Rana catesbeiana. In these the average bullfrog/rat-t½ ratio was 19.6 while the average bullfrog/man-t½ was 5.3. These ratios were close to expectations based on energy metabolism or adjusted allometric scaling. More importantly, however, these ratios showed a pronounced biphasic distribution with very slow elimination of drugs dependant on renal excretion (average bullfrog/rat-t½ = 45.0, n=3, SD 6.9) contrasting with an unexpectedly rapid elimination of drugs dependent on metabolic elimination (average bullfrog/rat-t½ = 6.9, n=6, SD 3.7). It is concluded that mammal to frog scaling based on energy turnover or body size adjusted for differences in taxa is valuable as an overall perspective but is very imprecise when applied to individual drugs; and that such estimates need to be “tailored” to take into account the distinctive characteristics of individual groups. In ranid frogs these would include a possible decrease in glomerular filtration attending drug administration and metabolic pathways that permit very rapid elimination of some lipophilic drugs.