Pharmacokinetics of proline-rich tripeptides in the pig

Tripeptides may possess bioactive properties. For instance, blood pressure lowering is attributed to the proline-rich tripeptides Ile-Pro-Pro (IPP), Leu-Pro-Pro (LPP), and Val-Pro-Pro (VPP). However, little is known about their absorption, distribution, and elimination characteristics. The aim of this study was to characterize the pharmacokinetic behavior of IPP, LPP, and VPP in a conscious pig model. Synthetic IPP, LPP, and VPP were administered intravenously or intragastrically (4.0 mg kg(-1) BW in saline) to 10 piglets (approximately 25 kg body weight) in the postabsorptive state. After intravenous dosing, the elimination half-life for IPP was significantly higher (P<0.001) than for LPP and VPP (2.5+/-0.1, 1.9+/-0.1, and 2.0+/-0.1 min, respectively). After intragastric dosing, however, the elimination half-lives were not significantly different between the peptides (9+/-1, 15+/-4, and 12+/-6 min, respectively). Maximum plasma concentrations were about 10 nmol l(-1) for the three tripeptides. The fraction dose absorbed was 0.077+/-0.010, 0.059+/-0.009, and 0.073+/-0.015%, for IPP, LPP, and VPP, respectively. Proline-rich tripeptides reach the blood circulation intact, with an absolute bioavailability of about 0.1% when administered via a saline solution. Because half-lives of absorption and elimination were maximally about 5 and 15 min, respectively, this suggests that under these conditions a bioactive effect of these tripeptides would be rather acute.