Oral and intravenous pharmacokinetics of taurine in sprague?￠????dawley rats: the influence of dose and the possible involvement of the proton?￠????coupled amino acid transporter, PAT1, in oral taurine absorption

摘要

Taurine is involved in various physiological processes, and one of the most abundant amino acids in human. The aim was to investigate the mechanism for intestinal absorption of taurine in????vivo using also in????vitro mechanistic studies. Taurine absorption was measured in male Sprague?￠????Dawley rats at 10?￠????997????mg/kg and 1?￠????30????mg/kg for oral and intravenous administration, respectively. Oral absorption was measured in the presence of substrates for the proton?￠????coupled amino acid transporter, PAT1, that is, 200????mg/kg proline (Pro) and sarcosine (Sar), and in the presence of 2?￠????Amino?￠????2?￠????norbornanecarboxylic acid (BCH) (200????mg/kg). BCH is not an inhibitor of PAT1 or the taurine transporter, TauT, hence it was included as a negative control. In vitro studies investigating the transport mechanism of taurine were conducted in human intestinal Caco?￠????2 cells. The pharmacokinetic investigations showed that intestinal taurine absorption was not saturable at the investigated doses, but that the time ( t max ) to reach the maximal plasma concentration ( C max ) increased with dose. Furthermore, Sar and Pro, but not BCH, decreased taurine C max . In vitro it was clearly shown that PAT1 mediated the cellular uptake of taurine and thereby facilitated the transepithelial taurine transport, which could be inhibited by Pro and Sar, but not BCH. In vivo and in????vitro results suggest that taurine absorption from the intestine is caused by PAT1.