A pharmacokinetic study of peritoneal absorption of glucose and alanine in rats: nutritional implications.

Abstract

The aim of this work was to study the serum bioavailability of glucose and alanine after bolus injection into the peritoneal cavity in Wistar rats and to determine the influence of their metabolism on the rate of absorption of these nutrients. A group of animals (n = 14) was infused intraperitioneally (i.p.) or i.v. with 2 microCi of nonmetabolizable L-[1-14C] glucose diluted in 5 mL of 5% D-glucose/250 g body wt, after which plasma radioactivity was determined. A second group of animals (n = 14) received, either i.p. or i.v., 3 microCi of nonmetabolizable D-[U-14C] alanine diluted in 2 mL of an iso-os-molar L-amino acid solution/250 g body wt, after which both plasma radioactivity and L-alanine concentration were determined. The constants of absorption from peritoneal cavity (Ka) and elimination from plasma (Ke) and the serum absolute bioavailability (BA(a)) after 8 h were calculated assuming a bicompartment pharmacokinetic model. L-glucose: Ka = 3.05 +/- 0.97 h-1; Ke = 0.40 +/- 0.12 h-1; BA(a) = 94% +/- 4%. D-alanine: Ka = 1.08 +/- 0.40 h-1; Ke = 0.11 +/- 0.06 h-1; BAa = 90% +/- 11%. L-alanine: Ka = 1.75 +/- 0.273 h-1; Ke = 0.02 +/- 0.01 h-1; BA(a) = 99% +/- 1%. No hyperglycemia, hypoglycemia, or glycosuria appeared in any case. The absorption rate from peritoneal cavity is nearly 10-fold higher than the elimination rate from plasma for the three substrates. Eight hours after i.p. injection an absolute bioavailability almost as high as after i.v. injection (i.e., close to 100%) was achieved. The metabolism of the nutrients seems to help the peritoneal absorption, as L-alanine is better absorbed then D-alanine. These results show that upon i.p. injection the studied nutrients are almost completely absorbed in a short period of time without hyperglycemia or neoglucogenesis and so suggest that their administration may be a feasible approach to feeding patients receiving peritoneal dialysis. This model could be applied to other compounds, such as peptides and disaccharides.