First-pass metabolism limits the intestinal absorption of enteral α-ketoglutarate in young pigs

Abstract

Our results in a previous study indicated that the portal absorption of intragastrically fed α-ketoglutarate (AKG) was limited in young pigs. Our aim was to quantify the net portal absorption, first-pass metabolism, and whole-body flux of enterally infused AKG. In study 1, we quantified the net portal nutrient absorption in young pigs (n = 9) given an intraduodenal infusion of milk replacer [10 mL/(kg·h)] and either saline (control) or 930 μmol/(kg·h) AKG for 4 h. In study 2, we quantified the luminal disappearance of a duodenal AKG bolus in young pigs (n = 7). In study 3, we quantified the whole-body kinetics of 13C-AKG metabolism when infused either enterally (n = 9) or intravenously (n = 9) in young pigs. In study 1, when compared with the control group, enteral AKG infusion increased (P < 0.01) the arterial (13.8 ± 1.7 vs. 27.4 ± 3.6 μmol/L) and portal (22.0 ± 1.4 vs. 64.6 ± 5.9 μmol/L) AKG concentrations and the net portal absorption of AKG [19.7 ± 2.8 vs. 95.2 ± 12.0 μmol/(kg·h)]. The mean fractional portal appearance of enterally infused AKG was 10.23 ± 1.3%. In study 2, the luminal disappearance of AKG was 663 μmol/(kg·h), representing 63% of the intraduodenal dose. In study 3, the whole-body 13C-AKG flux [4685 ± 666 vs. 801 ± 67 μmol/(kg·h)] was higher (P < 0.05) when given enterally than intravenously, but 13CO2 recovery was not different (37.3 ± 1.0 vs. 36.2 ± 0.7%dose). The first-pass splanchnic 13C-AKG utilization was ∼80%, of which 30% was oxidized to 13CO2. We conclude that the intestinal absorption of AKG is limited in young pigs largely due to substantial first-pass gastrointestinal metabolism. © 2006 American Society for Nutrition.