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)

Ondansetron is a 5-hydroxytryptamine3 receptor antagonist for the treatment of chemotherapy- and radiotherapy-induced nausea and emesis. A sensitive, accurate, and precise HPLC method for the determination of ondansetron in plasma is described. Samples are prepared by solid-phase extraction and, after chromatography of the extracts on a silica analytical column, ondansetron is detected by UV absorbance at 305 nm. The method is sensitive down to 1 ng/mL, at which concentration the coefficient of variation was 6.2% in a single assay run. Repeated analyses of quality control samples, nominally at 2 ng/mL, were carried out over a number of assay runs with a coefficient of variation of 5.5%. The method is specific for ondansetron with respect to endogenous plasma components, identified phase I metabolites, and some co-administered chemotherapeutic drugs. In sustained use over several months, and in support of the clinical development of ondansetron, the method has been shown to be robust. An application of the assay in the investigation of the pharmacokinetics of ondansetron in the young and elderly is described.
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PMID:Determination of ondansetron in plasma and its pharmacokinetics in the young and elderly. 183 13

To compare ondansetron (GR 38032F), a 5-hydroxytryptamine3-receptor antagonist, with metoclopramide in the prophylaxis of acute cisplatin-induced emesis, we conducted a double-blind crossover study in 97 patients scheduled to receive cisplatin (80 to 100 mg per square meter of body-surface area) for treatment of cancer. None had received chemotherapy before this trial. Among the 76 patients who satisfactorily completed both parts of the study, complete or nearly complete control of emesis (i.e., no episodes of emesis occurred, or only one or two) was achieved in 57 of 76 treatments (75 percent) with ondansetron and in 32 of 76 treatments (42 percent) with metoclopramide (P less than 0.001). Ondansetron was also more effective in controlling acute nausea, as assessed with a visual-analogue scale (P = 0.019) or a graded scale (P = 0.024). There was a significant preference among patients for ondansetron (55 vs. 26 percent; P = 0.006). Dystonic reactions were observed during three treatments with metoclopramide; both agents were otherwise well tolerated. We conclude that ondansetron is more effective than metoclopramide in the control of cisplatin-induced nausea and vomiting, and that this suggests that serotonin is an important mediator of this side effect.
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PMID:Comparison of the 5-hydroxytryptamine3 (serotonin) antagonist ondansetron (GR 38032F) with high-dose metoclopramide in the control of cisplatin-induced emesis. 213 3

In a cross-over design of a study of prevention of emesis induced by cancer chemotherapy done in Saitama Cancer Center, the efficacy of oral lorazepam was superior to that of i.v. domperidone. And then, we proceeded a parallel study with use of oral lorazepam and oral domperidone. However, in this situation lorazepam was not superior to domperidone despite accrual of more than 60 patients. Recently, a multi-institutional study has been started in October of 1988 in an evaluation of the efficacy and safety of the new anti-emetic drug of a 5HT3 receptor antagonist, ondansetron. Two methods of its administration were designed. In one study ondansetron was given 2 hr prior to non-platinum chemotherapy as an 2 or 8 mg dose by oral administration, followed by receiving it 6 hr and 12 hr after chemotherapy. In another study, it was given 15 min prior to cisplatin including chemotherapy as an 2 or 8 mg loading dose by i.v. injection over 5 min, followed by continuous infusion at a rate of 0.25 mg/h or 1 mg/h for 24 h, respectively. Efficacy was assessed by measurement of the number of episodes of retching and vomiting occurring in the 24h after administration of chemotherapy and by an assessment of nausea during the same period. This time the major efficacy category was adopted, which is made up of the complete responder and major responder categories of both vomiting and nausea. 19 patients were evaluable for efficacy in the non-platinum group; the major efficacy rates showed 45% in 2 mg-given group and 88% in 8 mg-given group, respectively. 108 patients were evaluable for efficacy in the cisplatin group: the major efficacy rates showed more than 70% in both 2 mg and 8 mg-given group. However, in the patients given more than 75 mg/mg2 of cisplatin, the major efficacy rates were 55% in the 2 mg-given group, compared to 73% in the 8 mg-given group. Ondansetron was well tolerated, with no significant drug-related adverse events.
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PMID:[Gastrointestinal toxicity induced by anticancer drugs--including new antiemetic drugs]. 214 Apr 98

Seventy-five breast cancer patients scheduled to receive a first course (in a new cycle) of cyclophosphamide, fluorouracil, and doxorubicin (FAC) or epirubicin (FEC) participated in a double-blind crossover study to compare the antiemetic efficacy and safety of ondansetron (GR38032), a 5-hydroxytryptamine3 (5-HT3) receptor antagonist, and metoclopramide. Ondansetron was given as an 8 mg loading dose (4 mg intravenously [IV] plus 4 mg orally) before chemotherapy followed by 8 mg every 8 hours orally for 3 to 5 days. Metoclopramide was given as an 80 mg loading dose (60 mg IV plus 20 mg orally) before chemotherapy followed by 20 mg every 8 hours orally for 3 to 5 days. A "period" interaction in the analysis of emetic response in the first 24 hours necessitated a parallel group analysis of first treatments only, 68 patients being assessable for this parameter. In the first 24 hours, complete or major control (zero to two emetic episodes) of emesis was achieved in 30 of 35 (86%) patients receiving ondansetron and in 14 of 33 (42%) patients receiving metoclopramide (P less than .001). Ondansetron was also more effective in reducing acute nausea. On days 2 to 3, the complete or major responses were significantly better with ondansetron (81% v 65%; P = .033), but there was no statistical difference in the control of nausea. There was a significant patient preference for ondansetron (63% v 26%; P = .001). Extrapyramidal reactions were observed in two metoclopramide treatments; both treatments were otherwise well tolerated. These results are consistent with serotonin (5-HT), being a significant neurotransmitter of cyclophosphamide/doxorubicin- or epirubicin/fluorouracil-induced emesis.
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PMID:A randomized double-blind comparison of ondansetron and metoclopramide in the prophylaxis of emesis induced by cyclophosphamide, fluorouracil, and doxorubicin or epirubicin chemotherapy. 214 Aug 54

The efficacy of ondansetron was compared with metoclopramide in the prophylaxis of nausea and vomiting induced by cyclophosphamide greater than or equal to 500 mg/m2 in combination with doxorubicin greater than or equal to 40 mg/m2 or epirubicin greater than or equal to 40 mg/m2. complete anti-emetic protection in the 24 h following chemotherapy was achieved in 26 of 40 (65%) patients treated with ondansetron compared with 17 of 42 (41%) patients treated with metoclopramide. Severe nausea was present in 3% of patients in the ondansetron group and 31% in the metoclopramide group. A worst day analysis of control of emesis and nausea on days 2 and 3 following chemotherapy also demonstrated ondansetron to be more effective than metoclopramide. Both treatments were well tolerated. Ondansetron is more effective as an anti-emetic than metoclopramide in this type of cytostatic therapy.
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PMID:A comparison of ondansetron with metoclopramide in the prophylaxis of chemotherapy-induced nausea and vomiting: a randomized, double-blind study. International Emesis Study Group. 214 87

Ondansetron, a 5HT3 antagonist, was given to 20 children aged 4 to 18 years who were undergoing treatment with the Australian and New Zealand Childhood Cancer Study Group Acute Lymphocytic Leukaemia (ALL) Study V Protocol. The study was open, dose ranging, and noncomparative, and designed to evaluate safety and efficacy of ondansetron in preventing nausea and vomiting caused by cyclophosphamide intravenous (IV) 1,000 mg/m2 day 1, and cytarabine IV subcutaneously (SC) 75 mg/m2 on days 2 to 5. Ten patients were given ondansetron 5 mg/m2 IV (group A) and subsequently another 10 patients were given ondansetron 3 mg/m2 IV (group B). Oral ondansetron was given for 14 doses, at the same dosage for both groups, commencing simultaneously with the IV infusion and continuing at 8 hourly intervals, ie, until day 5. The oral dose was based on surface area with the following schedule: 0.3 to 0.6 m2, 2 mg; 0.6 to 1 m2, 3 mg; and greater than 1 m2, 4 mg. Vomiting on the first day of chemotherapy was reported in group A by one patient and by one patient in group B. Vomiting during days 2 to 5 was reported by two group-A patients and by three group-B patients. Nausea was recorded on day 1 by one patient in group A, and two in group B, and on days 2 to 5 by three patients in group A, and by seven in group B. All patients were alert during treatment with ondansetron and there was no dystonia. There were no changes in renal function or hematology values that could be ascribed to the study drug. Transient elevations in bilirubin and liver enzymes were observed. We conclude that our results indicate that ondansetron is a safe and extremely effective single-agent antiemetic with minimal side effects, when administered both IV and orally.
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PMID:Prevention of cyclophosphamide/cytarabine-induced emesis with ondansetron in children with leukemia. 214 19

40 patients with metastatic breast cancer, under treatment with epirubicin (greater than 50 mg/m2) and cyclophosphamide (greater than 500 mg/m2), had an antiemetic therapy with Ondansetron 3 x 8 mg day, for a maximum of 10 cycles. A total of 128 treatment cycles were analysed. There was no reduction in antiemetic efficacy, regarding vomits/day and grade of nausea. 77% (31/40) had a steady or better control of vomiting during the whole treatment period. Only 23% experienced a reduction in the antiemetic efficacy in repeated therapy. 60-100% of the patients also had control of nausea (mild or none). Generally, there were no signs for a reduction of the antiemetic efficacy of Ondansetron in repeated therapy. There were neither clinically relevant side effects nor changes in laboratory values related to Ondansetron.
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PMID:[Long-term results of the anti-emetic effectiveness of the 5-HT3 antagonist ondansetron]. 214 77

Sixty five chemotherapy naive patients receiving cisplatin (50-120 mg/m2) containing chemotherapy participated in an evaluation of ondansetron, a 5-HT3 receptor antagonist, in the prophylaxis of acute and delayed nausea and emesis. Ondansetron was given as three 0.15 mg/kg doses intravenously (0.5 h before, 3.5 h and 7.5 h after cisplatin) for acute emesis followed by 8 mg orally 8-hourly for five days at 24 h post-cisplatin for delayed emesis. For acute emesis (first 24 h, n = 63), complete control was achieved in 34 patients (54%) and major control (1-2 episodes) in 16 patients (25%). Complete protection from acute nausea was achieved in 48 patients (76%). For delayed emesis (days 2-6, n = 55), 33 patients (60%) were completely protected or reported one to two episodes during the entire 5-day observation period; 63% reported only mild or no nausea. Ondansetron was well tolerated with no significant drug-related adverse events. These results are consistent with serotonin being a significant transmitter of cisplatin-induced emesis.
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PMID:Ondansetron (GR38032) in the prophylaxis of acute and delayed cisplatin-induced emesis. 214 9

Emesis in chemotherapy containing Cisplatinum (DDP) is still a therapeutical dilemma. Emesis and nausea cause the cessation of a potential curative therapy in up to 10% of patients treated with DDP. We studied the antiemetic effectiveness of the selective Serotonin (5HT3)-receptor-antagonist Ondansetron (GR 38032F, Glaxo) in patients receiving high dose platinum chemotherapy. All patients suffered from severe emesis and were refractory to any standard antiemetic regimen (Metoclopramid). We studied the efficacy of the new drug against acute and delayed emesis following platinum chemotherapy. All adverse events are listed. Thirty four courses (n = 17 patients) of a platinum-containing regimen were analyzed so far. A sufficient antiemetic efficacy was observed in 56% of the courses. In 32 of 34 course (94%) the patients preferred the new drug compared with the standard antiemetic regime (Metoclopramid). In most cases only minor adverse events--which do not require any medical therapy--occurred. The most common adverse events were headache, constipation, dry mouth, abdominal discomfort and elevation of liver enzyme level without any clinical symptoms. One patient needed bowel surgery for severe constipation based on widespread intra-abdominal carcinosis.
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PMID:[Refractory vomiting with cisplatin therapy. Prospective study with the serotonin receptor antagonist GR 38032F]. 215 May 51

In an open, drug-oriented phase-II/III-study 24 patients were treated with the 5-HT3-antagonist Ondansetron as an antiemetic drug for chemotherapy-induced nausea and emesis. Patients with treatment regimen containing cisplatin were excluded. All patients had suffered from severe nausea and vomiting under conventional antiemetic drugs during a previous identical chemotherapy cycle and were treated with 8 mg Ondansetron t.d. on the day of the chemotherapy and on the four following days. The drug was given with 90 cytostatic cycles ranging from 1 to 14 cycles per patient. Only 2 patients (8%) did not experience an improvement of their symptoms in any of the treatment cycles as measured by a self-conducted grading of nausea and by the frequency of vomiting in comparison to a previous treatment cycle under conventional antiemetic therapy. Eleven out of 18 patients, who were treated with Ondansetron more than once (61%) noted a diminished frequency of vomiting in each treatment cycle with Ondansetron. Sixty of the 90 therapy cycles with Ondansetron resulted in complete (no vomiting) or major (one to two vomits within 24 h following chemotherapy) protection from emesis (37 and 29 per cent, respectively). The most frequent side effect noted was obstipation (7 patients), followed by slight diffuse abdominal pain (4 patients, probably also due to chemotherapy) and slight to severe headache (3 patients, 1 patient was therefore withdrawn from the study). No other side effects were seen. In conclusion, our study indicates that Ondansetron is an effective and safe drug for the treatment of cytostatic drug-induced nausea and vomiting.
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PMID:[Ondansetron (GR 38032F), a competitive 5-HT3 receptor antagonist as an antiemetic in cytostatic drug-induced nausea and vomiting. An open, substance-oriented phase II/III study]. 215 May 52


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