Interaction of endogenous compounds in human and rat urine with P-glycoprotein.
The effect of hydrophobic extracts of human and rat urine on in-vitro P-glycoprotein (P-gp) function was examined, in terms of intra-, inter-individual variations, and physiological states. Six urine samples out of 7, obtained from one male subject on different days, suppressed P-gp function with different potencies. Similarly, 11 samples out of 15 different individuals (8 males and 7 females) inhibited P-gp function. Among them, urine from one female, obtained 1 month after delivery, showed a potent inhibitory effect. Another urine from a pregnant female, obtained 1 week before delivery, showed further potent inhibition on P-gp function. In addition, urine from normal rats strongly inhibited P-gp function at much lower concentrations than human urine, and the inhibitory potencies varied in diseased states; control (without urine extract)=experimental acute renal failure<experimental acute hepatic failure<normal rat urine. When human urine extract was separated by a two-dimensional thin-layer chromatography, several spot fractions inhibited P-gp function, and equilin was identified in one fraction as an endogenous P-gp inhibitor. In conclusion, it was demonstrated that urine contains many endogenous P-gp inhibitors, and their inhibitory potencies on P-gp function vary with intra- and inter-individual variations, and under different physiological states.[1]References
- Interaction of endogenous compounds in human and rat urine with P-glycoprotein. Murakami, T., Fukuda, T., Yumoto, R., Nagai, J., Kuramoto, T., Takano, M. Drug Metab. Pharmacokinet. (2002) [Pubmed]
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