The excretion of coumarin and hydroxycoumarins by the avian kidney in vivo.

The mechanics involved in the renal excretion of C14-labeled coumarin (C), 7-hydroxycoumarin (7HC) and 4-hydroxycoumarin (4HC) were studied in unanesthetized chickens by use of the Sperber technique. Analysis of urine collected during unilateral portal infusion of C, 4HC or 7HC indicated that the chicken excreted these coumarins almost entirely in conjugated form. Both 7HC and 4HC appeared in the urine only as the corresponding glucuronide. During C infusion, 84% of excreted radioactivity was identified as 7HC-glucuronide with only 8% appearing as a conjugate of open-ring metabolite o-hydroxyphenylacetic acid (HPAA). This demonstrated that, unlike other commonly-used laboratory animals, the chicken excretes C in a manner similar to man and suggests that this species is the most appropriate model for C pharmacodynamic studies applicable to humans. Comparative analysis of urines from the infused and control side kidneys indicated that neither C or 4HC undergoes net tubular secretion. In contrast 7HC was excreted by an active process which was significantly inhibited by simultaneous probenecid infusion. In addition it was demonstrated that the renal tubule cells conjugate 7HC as it crosses from blood to lumen suggesting that the kidney may contribute to the metabolism of C.