Interaction of hydrophobic components in female urine before and after childbirth with P-glycoprotein in vitro

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Various endogenous substances including substrates for ABC and SLC transporters expressed in the kidney are excreted into urine. In this study, the first urine in the morning (total 15 samples) and urine in the daytime (total 4 days, 18 samples) were collected at intervals from a young healthy woman before and after childbirth, to examine possible interactions of hydrophobic urine components (methanol extracts) with P-glycoprotein (P-gp) and multidrug resistance-associated proteins (MRPs). Four urine samples out of 12 collected before childbirth and one sample out of three obtained after childbirth suppressed P-gp function significantly. No relationship was observed between the P-gp inhibitory potencies of urine extracts and the timing of childbirth. The daytime urine samples showed a clear circadian rhythm, in which three first urine samples in the morning out of four showed the greater P-gp inhibitory potencies than other samples. Interaction of urine extracts with MRPs was no detected in Caco-2 cells. In conclusion, urine contains various endogenous P-gp substrates/inhibitor(s), and the concentration of endogenous P-gp inhibitor(s) was higher in the first urine in the morning. Pregnancy and lactation did not affect the P-gp inhibitory potencies of urine extracts.