van der Pijl Pieter C, Kies Arie K, Ten Have Gabriella A M, Duchateau Guus S M J E, Deutz Nicolaas E P
Unilever Food & Health Research Institute, Olivier van Noortlaan 120, 3133 AT Vlaardingen, The Netherlands.
Peptides. 2008 Dec;29(12):2196-202. doi: 10.1016/j.peptides.2008.08.011. Epub 2008 Aug 23.
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.
三肽可能具有生物活性特性。例如，富含脯氨酸的三肽异亮氨酸 - 脯氨酸 - 脯氨酸（IPP）、亮氨酸 - 脯氨酸 - 脯氨酸（LPP）和缬氨酸 - 脯氨酸 - 脯氨酸（VPP）具有降血压作用。然而，关于它们的吸收、分布和消除特性知之甚少。本研究的目的是在清醒猪模型中表征IPP、LPP和VPP的药代动力学行为。将合成的IPP、LPP和VPP静脉内或胃内给药（以4.0 mg kg(-1)体重的盐水溶液）给10只处于吸收后状态的仔猪（体重约25 kg）。静脉给药后，IPP的消除半衰期显著高于LPP和VPP（分别为2.5±0.1、1.9±0.1和2.0±0.1分钟，P<0.001）。然而，胃内给药后，这些肽之间的消除半衰期没有显著差异（分别为9±1、15±4和12±6分钟）。三种三肽的最大血浆浓度约为10 nmol l(-1)。IPP、LPP和VPP的吸收剂量分数分别为0.077±0.010、0.059±0.009和0.073±0.015%。富含脯氨酸的三肽完整地进入血液循环，通过盐溶液给药时绝对生物利用度约为0.1%。由于吸收和消除半衰期分别最大约为5分钟和15分钟，这表明在这些条件下这些三肽的生物活性作用将相当迅速。
