A Comparison of Pharmacokinetic Methods for In Vivo Studies of Nonmediated Glucose Absorption

Abstract

Two pharmacokinetic methods are used primarily to assess systematic bioavailability of orally dosed water-soluble compounds in vivo, but there have been no direct comparisons of the estimates obtained. The "area under the curve" (AUC) method employs a single oral dose of probe compound(s) followed by multiple blood sampling to obtain plasma concentration time curves. Separate injection of probe(s) followed by multiple blood sampling is used to calculate fractional elimination rate (K(el)) and distribution pool space (S). The "steady state feeding" method relies on ad lib. feeding of a marked diet, with a single blood sample taken to measure steady state feeding concentration of probe(s); K(el) is estimated from the decline in probe concentration in excreta after injection, with a single blood sample taken to estimate S. We compared these methods directly in the Australian red wattlebird (Anthochaera carnunculata), measuring absorption of (3)H-L-glucose. The K(el) values estimated using the steady state feeding protocol were significantly higher, and estimates of S and bioavailability consequently lower, compared with the AUC protocol. The AUC method relies on fewer assumptions and allows simultaneous comparisons of absorption by mediated and nonmediated (i.e., paracellular) mechanisms but cannot be easily applied to freely feeding animals. The steady state feeding method allows work with smaller species and exploration of the effects of feeding on nutrient uptake but requires careful attention to the validity of assumptions that increase error in the calculations.