Effect of cisplatin on the disposition of endogenous serotonin and its main metabolite, 5-hydroxyindole-3-acetic acid, in rats and dogs.
Emesis after the administration of cisplatin is a severe complication, and its treatment is an important problem clinically. Cisplatin forces the release of serotonin (5-HT) from enterochromaffin cells in the mucosa, and emesis occurs by the stimulation of 5-HT3 receptors. In this study, we established a simple and simultaneous method of determining 5-HT and its main metabolite, 5-hydroxyindole-3-acetic acid (5-HIAA), in plasma and urine by high performance liquid chromatography with electrochemical detection (HPLC-ECD), and determined the disposition of endogenous 5-HT and 5-HIAA after the administration of cisplatin in rats and dogs. In rats, we found no change in the plasma concentration of 5-HIAA after cisplatin administration, while a distinct increase was shown in the plasma concentration of 5-HT, but it was not significantly different from that of the control rats. The urinary excretion of 5-HIAA was also not different between the two groups. In dogs, we observed intense vomiting in all cisplatin treated dogs. However, we could not detect any change in the 5-HIAA or 5-HT level in the dog plasma. Furthermore, no significant difference in the urinary excretion of 5-HIAA was observed between the cisplatin group and the controls. From these results, the plasma concentration of 5-HT and the urinary excretion of 5-HIAA may not be suitable markers for the evaluation of emesis induced by anticancer drugs in dogs.
Nakajima
Y
Y
Department of Pharmacy, University of Tokyo Hospital, Japan.
Yamamoto
K
K
Yamada
Y
Y
Sawada
Y
Y
Iga
T
T
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D002945:Cisplatin / Q000494:pharmacology*; D004285:Dogs; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*
D000970:Antineoplastic Agents; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D002945:Cisplatin