-
Cancer Research and Treatment Dec 2004The aim of this study is to compare the antiemetic efficacy and tolerability of intravenous dolasetron mesylate and ondansetron in the prevention of acute and delayed...
Open-label, randomized comparison of the efficacy of intravenous dolasetron mesylate and ondansetron in the prevention of acute and delayed cisplatin-induced emesis in cancer patients.
PURPOSE
The aim of this study is to compare the antiemetic efficacy and tolerability of intravenous dolasetron mesylate and ondansetron in the prevention of acute and delayed emesis.
MATERIAL AND METHODS
From April 2002 through October 2002, a total of 112 patients receiving cisplatin- based combination chemotherapy were randomized to receive a single i.v. dose of dolasetron 100 mg or ondansetron 8 mg, 30 minutes before the initiation of chemotherapy. In the ondansetron group, two additional doses of ondansetron 8 mg were given at intervals of 2 to 4 hours. To prevent delayed emesis, dolasetron 200 mg p.o. daily or ondansetron 8 mg p.o. bid was administered from the 2(nd) days to a maximum of 5 days. The primary end point was the proportion of patients that experienced no emetic episodes and required no rescue medication (complete response, CR) during the 24 hours (acute period) and during Day 2 to Day 5+/-2 days (delayed period), after chemotherapy. The secondary end points included the incidence and severity of emesis.
RESULTS
105 patients were evaluable for efficacy. CR rates during the acute period were 36.0% for a single dose of dolasetron 100 mg, and 43.6% for three doses of ondansetron 8 mg. CR rates during the delayed period were 8.0% and 10.9%, respectively. There was no significant difference in the efficacy between the two groups. Adverse effects were mostly mild to moderate and not related to study medication.
CONCLUSIONS
A single i.v. dose of dolasetron 100 mg is as effective as three i.v. doses of ondansetron 8 mg in preventing acute and delayed emesis after cisplatin-based chemotherapy, with a comparable safety profile.
PubMed: 20368831
DOI: 10.4143/crt.2004.36.6.372 -
Journal of Clinical Pharmacology Oct 1996Dolasetron mesylate (MDL 73,147EF, Anzemet; Hoechst Marion Roussel, Laval, Canada) is a 5-HT3 receptor antagonist undergoing clinical evaluation for use as an antiemetic... (Comparative Study)
Comparative Study
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.
Topics: Aged; Antiemetics; Biological Availability; Chromatography, High Pressure Liquid; Cross-Over Studies; Humans; Indoles; Metabolic Clearance Rate; Quinolizines; Statistics, Nonparametric
PubMed: 8930777
DOI: 10.1002/j.1552-4604.1996.tb04757.x -
Anesthesiology Feb 1999
Topics: Anesthesia; Antiemetics; Granisetron; Humans; Indoles; Ondansetron; Postoperative Nausea and Vomiting; Quinolizines
PubMed: 9952135
DOI: 10.1097/00000542-199902000-00003 -
Journal of the American Animal Hospital... 2000
Review
Topics: Animals; Antiemetics; Cat Diseases; Cats; Dog Diseases; Dogs; Indoles; Nausea; Quinolizines; Vomiting
PubMed: 11105883
DOI: 10.5326/15473317-36-6-481 -
Biopharmaceutics & Drug Disposition Jan 1998Anzemet (dolasetron mesylate) is being developed for the prevention of chemotherapy-induced emesis and postoperative nausea and vomiting. Twenty-four healthy male... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Anzemet (dolasetron mesylate) is being developed for the prevention of chemotherapy-induced emesis and postoperative nausea and vomiting. Twenty-four healthy male subjects were orally dosed with dolasetron mesylate, 200 mg, after either an overnight fast or a high-fat breakfast. The ratio of the mean area under the plasma concentration-time curve of the reduced active metabolite (MDL 74,156) to infinity (AUC(0-infinity)) values in fed compared to fasting subjects was 86.3% with a 90% confidence interval for the ratio within (80, 125)%, indicating bioequivalence. The ratio of the mean MDL 74,156 maximum plasma concentration (Cmax) values was 70.6% in fed versus fasted subjects. The time to Cmax was statistically significantly longer after the high-fat breakfast (mean values, 1.11 h fasting and 1.80 h fed), probably due to delayed gastric emptying. It may be concluded that, although the rate of absorption was somewhat delayed, the extent of absorption did not change significantly when dolasetron mesylate was given with food.
Topics: Adult; Area Under Curve; Biological Availability; Chromatography, Liquid; Cross-Over Studies; Fasting; Food-Drug Interactions; Half-Life; Humans; Indoles; Mass Spectrometry; Quinolizines; Serotonin Antagonists; Tablets
PubMed: 9510981
DOI: 10.1002/(sici)1099-081x(199801)19:1<17::aid-bdd71>3.0.co;2-# -
Anesthesia and Analgesia May 2011
PubMed: 21451086
DOI: 10.1213/ANE.0b013e31821a9648 -
Annals of Oncology : Official Journal... Mar 2006Important progress in the prophylaxis of chemotherapy-induced acute and delayed emesis has been achieved but some fundamental needs still remain that requires new,... (Review)
Review
BACKGROUND
Important progress in the prophylaxis of chemotherapy-induced acute and delayed emesis has been achieved but some fundamental needs still remain that requires new, efficacious antiemetic drugs.
METHODS
A critical review of the results of published studies of aprepitant, a new NK1 receptor antagonist, and of palonosetron, a 5-HT3 receptor antagonist with a longer half-life.
RESULTS
Aprepitant combined with dexamethasone and a 5-HT3 antagonist significantly increased the control of acute emesis with respect to dexamethasone and a 5-HT3 antagonist alone after cisplatin and moderately emetogenic chemotherapy. For cisplatin nausea, aprepitant combined with dexamethasone significantly increased the control of delayed emesis with respect to dexamethasone alone, while for moderately emetogenic chemotherapy aprepitant is superior to a 5-HT3 antagonist in the control of delayed emesis. Palonosetron showed superior or similar efficacy to ondansetron and dolasetron in patients submitted to moderately emetogenic chemotherapy and similar efficacy to ondansetron in patients submitted to cisplatin.
CONCLUSIONS
More studies are necessary comparing aprepitant alone or combined with dexamethasone with respect to the recommended antiemetic drugs for the prevention of delayed emesis induced by cisplatin and moderately emetogenic chemotherapy as well as for palonosetron combined with dexamethasone with respect to other 5-HT3 antagonists combined with dexamethasone.
Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Dexamethasone; Drug Therapy, Combination; Humans; Isoquinolines; Medical Oncology; Morpholines; Nausea; Neoplasms; Palonosetron; Quinuclidines; Receptors, Serotonin, 5-HT3; Serotonin Antagonists; Vomiting
PubMed: 16608997
DOI: 10.1093/annonc/mdj936 -
Journal of Pharmaceutical and... Jan 1997A direct chiral HPLC method has been developed and validated to quantitate the enantiomers of MDL 74156, the primary metabolite of dolasetron mesylate, in human plasma...
A direct chiral HPLC method has been developed and validated to quantitate the enantiomers of MDL 74156, the primary metabolite of dolasetron mesylate, in human plasma over the concentration range 1.70-340 ng ml-1. Dolasetron mesylate is a 5-HT3 receptor antagonist that is currently being developed as an antiemetic. Both enantiomers of MDL 74154 and the internal standard (granisetron) were first extracted from alkanized plasma using methyl t-butyl ether. The analytes were then back-extracted into formic acid, separated on a ovomucoid-bonded HPLC column, and detected by native fluorescence (excitation wavelength of 274 nm and emission wavelength of 345 nm). The complete validation demonstrated the method to be accurate, precise, and specific for the direct quantitation of MDL 74156 enantiomers in human plasma. This procedure has been used on a routine basis to quantify the relative concentrations of each enantiomer of MDL 74 156 in both oral and intravenous pharmacokinetic studies of dolasetron mesylate in normal human volunteers.
Topics: Chromatography, High Pressure Liquid; Drug Stability; Humans; Indoles; Quinolizines; Reference Standards; Serotonin Antagonists; Stereoisomerism
PubMed: 8953495
DOI: 10.1016/s0731-7085(96)01827-4 -
Anaesthesia Sep 2005
Topics: Antiemetics; Female; Humans; Indoles; Middle Aged; Postoperative Care; Postoperative Nausea and Vomiting; Quinolizines; Tachycardia, Supraventricular
PubMed: 16115265
DOI: 10.1111/j.1365-2044.2005.04347.x -
Journal of Clinical Anesthesia Dec 2007A 52-year-old woman with hypertension and Graves' disease was scheduled for surgical removal of a meningioma. Intraoperative events were significant for hypotension...
A 52-year-old woman with hypertension and Graves' disease was scheduled for surgical removal of a meningioma. Intraoperative events were significant for hypotension requiring a vasopressin infusion. Prophylactic dolasetron was administered to the patient before emergence. The patient's trachea was easily extubated and she was neurologically intact at the end of the surgical procedure. On transport to the neurological intensive care unit, the patient developed torsades de pointes, requiring cardiopulmonary resuscitation, before a return to normal sinus rhythm.
Topics: Adrenergic beta-Antagonists; Amiodarone; Anti-Arrhythmia Agents; Antiemetics; Cardiopulmonary Resuscitation; Electrocardiography; Female; Follow-Up Studies; Graves Disease; Humans; Hypertension; Hypotension; Indoles; Intraoperative Complications; Intubation, Intratracheal; Meningeal Neoplasms; Meningioma; Middle Aged; Postoperative Complications; Propanolamines; Quinolizines; Risk Factors; Torsades de Pointes; Vasoconstrictor Agents; Vasopressins
PubMed: 18083478
DOI: 10.1016/j.jclinane.2007.03.012