Melanin affinity: a possible explanation of isoxsuprine retention in the horse

Isoxsuprine is used in veterinary medicine as a vasodilating agent. The drug has been detected in the urine of horses up to 6 weeks after the cessation of administration. In the present study, the distribution pattern of 3H-isoxsuprine was investigated using whole body autoradiography in mice to find a possible site of retention. Melanin was the only place of retention identified. Additional in vitro studies showed an affinity of isoxsuprine to both melanin and keratin. The K(d) values were 0.02 mmol/l and 1 mmol/l, and the B(max) values were 0.2 micromol/mg and 2 micromol/mg, respectively. A low affinity site with approximately the same K(d) and B(max) as keratin was also detected for melanin. 3H-isoxsuprine was found to have affinity to pigmented horse skin after incubation in vitro and microautoradiography. We believe that affinity to melanin and possibly also to keratin can cause retention of the drug in the body and therefore explain the prolonged excretion of low levels of isoxsuprine in the horse.