Although systemic exposure to peptides, such as Gly–Pro–Hyp, Pro–Hyp, and Gly–Pro, has been reported following administration of collagen hydrolysates from fish scale and porcine skin in vivo, the individual peptide pharmacokinetics remain unknown. We administered the three peptides individually to rats via the intravenous (5 mg/kg) and intragastric (100 mg/kg) routes and then monitored systemic exposure and urinary excretion. The peptides in biological samples were analyzed via liquid chromatography/tandem mass spectrometry. Gly–Pro–Hyp tended to exhibit higher first-pass metabolism than Pro–Hyp; the absolute oral bioavailabilities of Gly–Pro–Hyp and Pro–Hyp were 4.4% and 19.3%, respectively. Gly–Pro levels were very low in the systemic circulation. Pro–Hyp biotransformed from Gly–Pro–Hyp behaved similarly to Pro–Hyp alone when administered orally. Flip-flop kinetics (elimination rate ≫ absorption rate) were evident, probably reflecting transporter-mediated slow absorption. A double-peak phenomenon was observed for Gly–Pro–Hyp and Pro–Hyp when administered orally, and 5.9% ± 2.6% and 1.9% ± 0.3% of each dose were excreted in urine after intravenous administration, respectively. Urinary recovery of Gly–Pro was limited to 0.4% ± 0.5% of the intravenous dose. This work represents the first individual pharmacokinetics of Gly–Pro–Hyp, Pro–Hyp, and Gly–Pro in vivo.

中文翻译：

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胶原二肽（Gly–Pro 和 Pro–Hyp）和三肽（Gly–Pro–Hyp）在大鼠体内的药代动力学


尽管已有报道在体内施用来自鱼鳞和猪皮的胶原蛋白水解物后全身暴露于肽，例如Gly-Pro-Hyp、Pro-Hyp和Gly-Pro，但单个肽的药代动力学仍然未知。我们通过静脉注射（5 mg/kg）和胃内注射（100 mg/kg）途径分别给大鼠施用三种肽，然后监测全身暴露和尿液排泄。通过液相色谱/串联质谱分析生物样品中的肽。 Gly-Pro-Hyp 往往表现出比 Pro-Hyp 更高的首过代谢； Gly-Pro-Hyp 和 Pro-Hyp 的绝对口服生物利用度分别为 4.4% 和 19.3%。体循环中的 Gly-Pro 水平非常低。口服给药时，由 Gly-Pro-Hyp 生物转化的 Pro-Hyp 表现与单独的 Pro-Hyp 相似。触发器动力学（消除率≫吸收率）很明显，可能反映了转运蛋白介导的缓慢吸收。口服给药时，Gly-Pro-Hyp和Pro-Hyp出现双峰现象，静脉给药后各剂量分别有5.9%±2.6%和1.9%±0.3%从尿中排出。尿中 Gly-Pro 的回收率仅限于静脉剂量的 0.4% ± 0.5%。这项工作代表了 Gly-Pro-Hyp、Pro-Hyp 和 Gly-Pro 体内第一个单独的药代动力学。