Human metabolism of dolasetron mesylate, a 5-HT3 receptor antagonist.

Article Details

Citation

Copy to clipboard

Reith MK, Sproles GD, Cheng LK

Human metabolism of dolasetron mesylate, a 5-HT3 receptor antagonist.

Drug Metab Dispos. 1995 Aug;23(8):806-12.

PubMed ID

7493546 [ View in PubMed

]

Abstract

Dolasetron mesylate is a selective and potent 5-HT3 receptor antagonist. This drug is currently in development for the treatment of nausea and vomiting in chemotherapy. The metabolism of dolasetron mesylate was studied in six healthy male volunteers who were given a single 300 mg oral dose of [14C]dolasetron mesylate. An average of 59% of the total radioactivity was recovered in the urine and 25% in the feces. Metabolites were quantitated in urine samples taken up to 36 hr postdose. Reduced dolasetron (RD) accounted for 17-54% of the dose in urine. Hydroxylated metabolites of RD made up no more than 9% of the dose in urine. Most of the remaining urinary radioactivity consisted of conjugated metabolites of RD and hydroxy RD. Hydrolysis of selected urine samples showed that the glucuronide of RD was the most abundant conjugate in urine. A small percentage of the dose (< 1%) in urine was identified as the N-oxide of RD. Analysis of urine samples by chiral HPLC indicated that the R(+):S(-) ratio of RD was approximately 9:1.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Dolasetron	5-hydroxytryptamine receptor 3A	Protein	Humans	Yes	Antagonist	Details