Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Selective 5-HT3 antagonists have proven to be safe and effective for the prevention of chemotherapy-induced nausea and vomiting. Dolasetron is a new highly selective addition to this class of antiemetics that has been shown to have significant antiemetic activity in patients receiving cisplatin-containing regimens. This pilot study was designed to evaluate the antiemetic efficacy of dolasetron in cancer patients receiving doxorubicin and/or cyclophosphamide. This study used an open-label, non-randomized design to evaluate the efficacy and safety of intravenous dolasetron in the prevention of emesis in patients receiving doxorubicin (25-75 mg/m2) and/or cyclophosphamide (400-1200 mg/m2). Sixty-nine patients received a single, intravenous dose of dolasetron over 15-20 min beginning 30 min prior to the start of chemotherapy. Dose levels of dolasetron studied were: 0.3, 0.6, 1.2, 1.8 and 2.4 mg/kg. Patients were monitored for emesis, nausea and adverse events for 24h after the start of chemotherapy. Overall, 61% of patients experienced complete control of emesis. No significant trend towards increased antiemetic efficacy (P = 0.076) or nausea control with increasing dolasetron dose was noted, although the power to detect significant differences was limited by the small number of patients on the 0.3-mg/kg and 2.4-mg/kg dose levels. Age, gender, and type of chemotherapy were significant predictors of complete antiemetic control. Adverse events were generally mild and included headache, chills, lightheadedness, fever, diarrhea, dizziness, and asymptomatic prolongation of ECG intervals. Intravenous dolasetron is safe and effective in the prevention of emesis induced by doxorubicin and/or cyclophosphamide.
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PMID:Dose-ranging evaluation of the antiemetic efficacy of intravenous dolasetron in patients receiving chemotherapy with doxorubicin or cyclophosphamide. 867 51

The aim of this work was to measure the safety and efficacy of single i.v. doses of dolasetron mesilate for the control of emesis caused by single high-dose (at least 6 Gy) radiotherapy to the upper abdomen. The double-blind, placebo-controlled, multicenter study stratified patients on the basis of being naive or nonnaive to radiotherapy. Patients with or without a history of previous chemotherapy were enrolled. Patients were randomized to receive placebo or 0.3, 0.6, or 1.2 mg/kg dolasetron mesilate 30 min before radiotherapy, then monitored for 24 h. Antiemetic efficacy was assessed from the time to the first emetic episode or rescue, from whether there was a complete response (0 emetic episodes /no rescue medication) or a complete-plus-major response (0-2 emetic episodes/no rescue medication), from the severity of nausea (rated by patients and the investigator), and from the investigator's assessment of efficacy. Fifty patients completed the study (owing to changing medical practice, enrollment objectives were not met; consequently, no significant linear dose trend was expected). Pooled dolasetron was superior to the placebo in its effect on the time to first emesis or rescue in radiotherapy-nonnaive patients (P = 0.015). Dolasetron was statistically superior to the placebo in the overall population on the basis of a complete plus major response: 54%, 100%, 93%, and 83% for the placebo and 0.3-, 0.6-, and 1.2-mg/kg doses respectively (P = 0.002). The low response in the highest dose group may be due to an imbalance in the number of chemotherapy-nonnaive patients in that group. Dolasetron was superior to the placebo on the basis of nausea assessed by the investigator (P = 0.024) and administration of rescue medication (P = 0.006). Complete response at the 0.3-mg/ kg dose was superior to results with the placebo (P = 0.050). Treatment-related adverse events were rare, mild to moderate in intensity, and evenly distributed across the four groups. Overall, dolasetron mesilate was effective and well-tolerated in the control of single, high-dose radiotherapy-induced emesis.
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PMID:A double-blind, placebo-controlled trial of i.v. dolasetron mesilate in the prevention of radiotherapy-induced nausea and vomiting in cancer patients. 888 32

The potent serotonin receptor (5-HT3) antagonists are new highly selective agents for the prevention and control of chemotherapy-induced nausea and vomiting that have been shown to be comparable to or more effective than traditional metoclopramide regimens. This study was designed to compare the antiemetic efficacy of dolasetron and metoclopramide in chemotherapy-naive and non-naive cancer patients receiving high-dose cisplatin-containing chemotherapy. This multicentre, double-blind, randomized trial compared the efficacy and safety of single i.v. doses of dolasetron mesilate salt (1.2 or 1.8 mg/kg) and metoclopramide (7 mg/kg) in 226 patients for the prevention of acute emesis and nausea associated with the administration of high-dose (> or = 80 mg/m2) cisplatin. Efficacy and safety were evaluated for 24 h. Complete responses were achieved by 57%, 48%, and 35% of patients given dolasetron mesilate 1.8 mg/kg (P = 0.0009 vs metoclopramide), dolasetron mesilate 1.2 mg/kg (P = 0.0058 vs metoclopramide), and metoclopramide, respectively. Overall, dolasetron was significantly more effective than metoclopramide for time to first emetic episode, nausea, patient satisfaction, and investigator global assessment of efficacy. Males, chemotherapy-naive patients, and alcoholics had higher response rates. Dolasetron was well tolerated, with mild-to-moderate headache most commonly reported. Twelve percent of patients receiving metoclopramide reported extrapyramidal symptoms compared with 0% of patients receiving dolasetron. In conclusion, dolasetron mesilate was effective for the prevention of CINV with high-dose cisplatin. Single i.v. doses of dolasetron mesilate were more effective than 7 mg/kg metoclopramide in preventing nausea and vomiting induced by highly emetogenic cisplatin-containing chemotherapy. In addition, 1.8 mg/kg dolasetron mesilate consistently produced the highest response rates and appears to be the most effective dose for further clinical development.
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PMID:A double-blind, multicentre comparison of intravenous dolasetron mesilate and metoclopramide in the prevention of nausea and vomiting in cancer patients receiving high-dose cisplatin chemotherapy. 901 Sep 86

The newer 5-hydroxytryptamine type 3 (5-HT3) antagonists are sometimes considered for routine prophylaxis of postoperative nausea and vomiting (PONV) in high-risk patients. This multicenter, randomized, double-blind, placebo-controlled study compared the efficacy and safety of three single intravenous (IV) doses of dolasetron mesylate salt (12.5, 25, or 50 mg) for the prevention of PONV in 635 females undergoing outpatient laparoscopic gynecologic surgery. Antiemetic efficacy was evaluated over a 24-h postoperative period by recording the number and timing of emetic episodes; effects on nausea were evaluated by a visual analog scale (VAS). The proportion of complete responders (no emetic episodes and no escape medication in 24 h) was significantly higher with each dolasetron mesylate dose (> 50% for each dose; P < or = 0.0003) than with placebo (30.6%). Fewer patients given dolasetron required or requested escape antiemetic medication compared with placebo (P < 0.0003). Dolasetron-treated patients had significantly (P < 0.0357) lower median postdose maximum nausea VAS scores compared with placebo-treated patients. Patient satisfaction with dolasetron was high and, overall, was significantly (P = 0.0131) greater than that with placebo. Dolasetron was an effective and well tolerated preventive treatment for PONV resulting from laparoscopic gynecologic surgery.
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PMID:Intravenous dolasetron for the prevention of postoperative nausea and vomiting after outpatient laparoscopic gynecologic surgery. 902 22

Fractionated cisplatin-containing regimens are routinely used for chemotherapy in certain types of cancer. Dolasetron has been shown to be effective in preventing acute emesis related to high-dose cisplatin chemotherapy over 24 h; its effectiveness has not been evaluated in fractionated cisplatin-containing chemotherapy. This trial was designed to assess the efficacy of dolasetron alone or dolasetron plus dexamethasone in preventing nausea and vomiting related to fractionated cisplatin chemotherapy. The patients were 210 cancer in-patients, who were randomised to receive 100 mg dolasetron i.v. or 100 mg dolasetron i.v. plus 20 mg dexamethasone before chemotherapy primarily with cisplatin (15-50 mg/m2) infused over < or =4 h for at least 2 but not more than 5 consecutive days. Dolasetron was administered to all patients 30 min before cisplatin. Dexamethasone was administered in double-blind fashion 5 min before cisplatin. Efficacy was measured at hour 24 of each study day using complete response (no vomiting and no rescue medication) and maximum severity of nausea, self-assessed by patients using a 100mm visual analogue scale. Most (198) of the patients completed the study and were evaluable. Overall complete response rates were significantly higher in the dolasetron plus dexamethasone group than in the dolasetron only group (72.9% vs. 40.8%, respectively; P<0.0001). Complete response rates on each study day were also significantly higher with dolasetron plus dexamethasone than with dolasetron alone (P<0.029), with an attenuated efficacy in the delayed phase in both groups. Chi-square test and logistic regression applied to daily response rates indicated a significant influence of treatment (day 1: P = 0.0002, day 2: P<0.0001, day 3: P = 0.0007, day 4: P = 0.0007, day 5: P = 0.029). Treatment and duration of chemotherapy exerted the only statistically significant subgroup effects on complete response (P<0.0001). Both treatments were administered safely. As seen with other 5-HT3 receptor antagonist antiemetics, the addition of dexamethasone to dolasetron significantly increases effectiveness in preventing nausea and vomiting related to fractionated cisplatin chemotherapy. Both dolasetron and dolasetron plus dexamethasone were well tolerated.
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PMID:A double-blind, randomised, parallel study comparing intravenous dolasetron plus dexamethasone and intravenous dolasetron alone for the management of fractionated cisplatin-related nausea and vomiting. 1065 Aug 98

In a multicentre, randomized, double-blind, placebo-controlled dose-ranging study, 1030 patients undergoing outpatient surgery with general anaesthesia received i.v. dolasetron mesylate (12.5, 25, 50, or 100 mg) or placebo. The principal outcome measure was the proportion of patients who were free of emesis or rescue medication for the 24-h period after the study drug was given; the subsidiary outcome measure was survival time without rescue medication. Effects on nausea were quantified using a visual analogue scale. Compared with placebo, a complete response was significantly higher when all four dolasetron doses were combined (49% vs. 58%, P =0.025). In females, dolasetron, 12.5-mg, dolasetron provided maximum clinical benefit (effectiveness compared with adverse events), with no additional benefit in complete response rates or nausea visual analogue scale scores at higher doses. No significant differences were observed in complete response for any dolasetron dose in males compared with placebo. The majority of adverse events reported were mild or moderate. Dolasetron provided well-tolerated, safe, and effective prophylaxis for post-operative nausea and vomiting with maximum effectiveness observed at a dose of 12.5 mg.
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PMID:Dolasetron for the prevention of postoperative nausea and vomiting following outpatient surgery with general anaesthesia: a randomized, placebo-controlled study. The Dolasetron PONV Prevention Study Group. 1075 40

BACKGROUND: The relative efficacy of antiemetics for the treatment of postoperative nausea and vomiting (PONV) is poorly understood. METHODS: Systematic search (MEDLINE, Embase, Cochrane Library, bibliographies, any language, to 8.2000) for randomised comparisons of antiemetics with any comparator for the treatment of established PONV. Dichotomous data on prevention of further nausea and vomiting, and on side effects were combined using a fixed effect model. RESULTS: In seven trials (1,267 patients), 11 different antiemetics were tested without placebos; these data were not further analysed. Eighteen trials (3,809) had placebo controls. Dolasetron 12.5-100 mg, granisetron 0.1-3 mg, tropisetron 0.5-5 mg, and ondansetron 1-8 mg prevented further vomiting with little evidence of dose-responsiveness; with all regimens, absolute risk reductions compared with placebo were 20%-30%. The anti-nausea effect was less pronounced. Headache was dose-dependent. Results on propofol were contradictory. The NK1 antagonist GR205171, isopropyl alcohol vapor, metoclopramide, domperidone, and midazolam were tested in one trial each with a limited number of patients. CONCLUSIONS: Of 100 vomiting surgical patients receiving a 5-HT3 receptor antagonist, 20 to 30 will stop vomiting who would not have done so had they received a placebo; less will profit from the anti-nausea effect. There is a lack of evidence for a clinically relevant dose-response; minimal effective doses may be used. There is a discrepancy between the plethora of trials on prevention of PONV and the paucity of trials on treatment of established symptoms. Valid data on the therapeutic efficacy of classic antiemetics, which have been used for decades, are needed.
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PMID:Treatment of established postoperative nausea and vomiting: a quantitative systematic review. 1173 64

In a randomized, placebo-controlled, double-blind trial, we compared the efficacy of dolasetron, dexamethasone, and metoclopramide in a preventing postoperative nausea and vomiting in women undergoing breast surgery. Patients were allocated randomly to one of four groups (20 patients each): group A received 12.5 mg dolasetron, group B received 8 mg dexamethasone, group C received 20 mg metoclopramide, and group D received placebo intravenously. If patients complained of retching or vomiting or if patients demanded an antiemetic, 1.25 mg droperidol was administered intravenously. To quantify postoperative nausea and vomiting, the following score was used: 0 = no nausea, 1 = nausea, 2 = retching, 3 = single vomiting, 4 = multiple vomiting. Dolasetron and dexamethasone reduced the postoperative nausea and vomiting score significantly (p < 0.02 versus metoclopramide; p < 0.0001 versus placebo). Metoclopramide also reduced the postoperative nausea and vomiting score (p < 0.02 versus placebo). Fisher's exact test showed a significant reduction of vomiting in the dolasetron and dexamethasone groups compared with metoclopramide-treated patients (p < 0.007) and placebo-treated patients (p < 0.000006) and a significantly lower rate of nausea in comparison to the placebo group (p < 0.009). There were no significant differences between the metoclopramide and the placebo groups (using Fisher's exact test). The use of postoperative droperidol was significantly lower in both the dolasetron group (p < 0.04 versus metoclopramide; p < 0.0001 versus placebo) and dexamethasone group (p < 0.04 versus metoclopramide; p < 0.0001 versus placebo), as well as in the metoclopramide group (p < 0.02 versus placebo). Intravenous dolasetron and dexamethasone were equally effective and both are more effective than metoclopramide for preventing vomiting after breast surgery. Also both were significantly superior to either metoclopramide or placebo for postoperative nausea and vomiting and the need for droperidol rescue.
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PMID:Dolasetron decreases postoperative nausea and vomiting after breast surgery. 1636 99

This study assessed the efficacy and safety of dolasetron compared with ondansetron for the prevention of nausea and vomiting during high-dose myeloablative chemotherapy followed by peripheral blood stem cell support. Twenty centers randomized 197 patients to receive dolasetron 100 mg intravenously (I.V.) followed 8-12 hours later by a single oral dose of dolasetron 100 mg or ondansetron 32 mg I.V., followed 8-12 hours later by a single oral dose of ondansetron 8 mg during high-dose chemotherapy (HDC) regimens for breast cancer (n = 96; 48.7%), non-Hodgkin's lymphoma (n = 83; 42.1%), or Hodgkin's disease (n = 18; 9.1%). All patients received a daily I.V. bolus of dexamethasone 10 mg with study antiemetic agents and a continuous infusion of diphenhydramine, lorazepam, and dexamethasone (ie, BAD pump) throughout the course of the study, with patient-controlled on-demand bolus doses as needed. After completing a daily diary of emetic episodes and rescue medication use, 164 of 197 patients were evaluable. Total plus complete responses (no emesis, no nausea, no rescue) over the entire study period were achieved in 45.7% and 46.9% of patients on the dolasetron and ondansetron arms, respectively. Dolasetron and ondansetron were well-tolerated. This study demonstrates that dolasetron and ondansetron are equally safe and effective in the prevention of nausea and vomiting associated with HDC (P = 0.955).
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PMID:A randomized, multicenter, open-label comparison of the antiemetic efficacy of dolasetron versus ondansetron for the prevention of nausea and vomiting during high-dose myeloablative chemotherapy. 1862 98

Objectives The objectives were to evaluate the pharmacokinetics (PK) of subcutaneous (SC) and intravenous (IV) dolasetron and the pharmacodynamics (PD) of SC dolasetron in healthy cats. Methods Five cats with unremarkable complete blood count, serum biochemistry and urinalyses were utilized. In the PK study, cats received 0.8 mg/kg SC and IV dolasetron in a crossover format. Serum samples were obtained via a jugular catheter at 0, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 36 and 48 h after the administration of dolasetron. Dolasetron and the active metabolite hydrodolasetron were measured using liquid chromatography/tandem mass spectrometry. Non-compartmental PK analysis was performed. In the PD study, SC dolasetron (0.8 mg/kg and 1.0 mg/kg) and saline were administered 30 mins prior to administration of 0.44 mg/kg intramuscular xylazine in a randomized three-way crossover. Number of emetic events, lip licks, time to onset of emesis and visual nausea score were scored by a blinded observer. Results In the PK study, dolasetron was quickly metabolized to the active metabolite hydrodolasetron, limiting assessment of dolasetron PK parameters. Median (range) PK parameters for IV hydrodolasetron were as follows: maximum serum concentration (Cmax) 116 ng/ml (69-316 ng/ml), time to maximum concentration (Tmax) 0.5 h (0.3-0.5 h), half-life 3.3 h (2.9-7.2 h) and area under the curve until the last measurable concentration (AUClast) 323 h/ng/ml (138-454 h/ng/ml). Median (range) PK parameters for SC hydrodolasetron were as follows: Cmax 67.9 ng/ml (60.4-117 ng/ml), Tmax 0.5 h (0.5-1.0 h), half-life 3.8 h (2.9-5.3 h) and AUClast 437 h/ng/ml (221.5-621.8 h/ng/ml). There was no significant difference in exposure to hydrodolasetron between the routes of administration. With regard to PD, when dolasetron was administered prior to xylazine, there was no significant difference in the mean number of emetic events, lip licks, time to onset of emesis or visual nausea score when compared with saline. Conclusions and relevance Administration of 0.8 mg/kg dolasetron does not maintain serum concentrations of active metabolite for 24 h. Administration of dolasetron at 0.8 mg/kg and 1 mg/kg did not prevent xylazine-induced vomiting. Additional feline dose studies are needed to determine if a higher dose is efficacious.
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PMID:Preliminary pharmacokinetics of intravenous and subcutaneous dolasetron and pharmacodynamics of subcutaneous dolasetron in healthy cats. 2890 67


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