Meeting Abstract

P2.85A  Thursday, Jan. 5  A comparison of pharmacokinetic methods for in vivo studies of non-mediated glucose absorption NAPIER, K.R.*; MCWHORTER, T.J.; MARTINEZ DEL RIO, C.; FLEMING, P.A.; Murdoch Univ., Western Australia and Univ. of Wyoming, Laramie; Murdoch Univ., Western Australia and Univ. of Adelaide, South Australia; Univ. of Wyoming, Laramie; Murdoch Univ., Western Australia knapier@uwyo.edu

Two pharmacokinetic methods are primarily used to assess systematic bioavailability (f) of orally dosed water-soluble compounds in vivo. The ‘area under the curve’ (AUC) method employs a single oral dose of probe compounds followed by multiple blood sampling to obtain plasma concentration time curves. Fractional elimination rate (Kel) and distribution pool space (S) are estimated from multiple blood samples following a separate injection of probes. The ‘steady-state feeding’ method relies on ad libitum feeding of a marked diet, with the concentration probes during steady-state feeding measured with one blood sample. Kel is estimated from the decline in probe concentration in excreta with S estimated from one blood sample. We compared these methods in the Australian red wattlebird measuring absorption of 3H-L-glucose. Kel values estimated using the steady-state feeding protocol were significantly higher, and estimates of S and f consequently lower, compared with the AUC protocol. The steady-state feeding method appears sensitive to disruptions of steady-state feeding. Higher Kel values may also reflect differences in renal function, since animals fed ad libitum. The AUC method relies on fewer assumptions and allows simultaneous comparisons of absorption by mediated and non-mediated (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.