Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P46098 (5-HT3 receptor)
 2,290 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dolasetron mesylate (MDL 73,147EF, Anzemet; Hoechst Marion Roussel, Laval, Canada) is a 5-HT3 receptor antagonist undergoing clinical evaluation for use as an antiemetic agent. The pharmacokinetics of dolasetron and its reduced metabolite (MDL 74,156) were studied after administration of single intravenous and oral doses of dolasetron mesylate 2.4 mg/kg in 18 healthy elderly subjects. Expressed as the dolasetron base, this dose was 1.8 mg/kg. Dolasetron was rapidly metabolized to the reduced metabolite, which appeared in plasma within 10 minutes after intravenous or oral administration. The mean half-life (t1/2) of dolasetron was 0.24 hours after intravenous administration and 0.50 hours after oral administration. The pharmacokinetic parameters of the reduced metabolite were similar after intravenous and oral administration. The apparent absolute bioavailability of the reduced metabolite was 89%, and it had an elimination t1/2 of approximately 7 hours and an apparent volume of distribution (Vd beta) of 4.69 L/kg. Dolasetron was not detected in urine. Metabolites were excreted in urine almost completely within 24 hours of administration. The primary metabolite detected in urine was the (+)-enantiomer of the reduced metabolite, which accounted for 25.35% (+/- 7.79%) and 18.88% (+/- 7.65%) of the intravenous and oral doses, respectively. Hydroxylated metabolites accounted for 5% or less of the total dose via either route. The pharmacokinetics of the reduced metabolite after single intravenous or oral doses in elderly volunteers were consistent with pharmacokinetics observed in both young healthy men and cancer patients receiving high-dose cisplatin chemotherapy. Dosage adjustments of dolasetron mesylate on the basis of age do not appear to be necessary.
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PMID:Pharmacokinetics of single intravenous and oral doses of dolasetron mesylate in healthy elderly volunteers. 893 Jul 77

Nausea and vomiting continue to rank as important side effects for cancer patients receiving chemotherapy. The class of drugs known as the 5-HT3 receptor antagonists have become widely used for chemotherapy-induced nausea and vomiting, and are considered a standard part of care for moderately- and highly-emetogenic chemotherapy in combination with corticosteroids. Ondansetron (Zofran, Glaxo Wellcome), granisetron (Kytril, SmithKline Beecham) and dolasetron (Anzemet, Hoechst Marion Roussel) are commercially available in the US. Intravenous forms of all three drugs have demonstrated efficacy in preventing acute (< or = 24 h following chemotherapy) nausea and emesis due to moderately- and highly-emetogenic chemotherapy. Oral forms of the drugs have been shown to be effective in prevention of nausea and emesis due to moderately-emetogenic chemotherapy. More recently, oral 5-HT3 receptor antagonists have demonstrated efficacy in the prevention of nausea and vomiting due to highly-emetogenic chemotherapy as well. Comparative trials between the three agents have shown no clinically important differences in outcome and they should be considered clinically equivalent. Optimal oral anti-emetic regimens for high-dose chemotherapy with bone marrow or stem cell transplantation remain to be determined and future oral studies should target this population. In general, the decision of which 5-HT3 receptor antagonist to select for formulary inclusion should be based on the dose of anti-emetic used and the acquisition cost of the agents being compared. The oral route should be used whenever possible.
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PMID:Advances in use of the 5-HT3 receptor antagonists. 1124 43