Ondansetron is effective in decreasing postoperative nausea and vomiting.

The efficacy of ondansetron, a selective 5-HT3 receptor antagonist, in preventing postoperative nausea and vomiting in surgical patients was studied. Fifty women were randomized in a double-blind manner to receive either two 8 mg doses of intravenous ondansetron or two doses of placebo vehicle: the first given just before general anesthesia induction and the second 8 hours later. During the first 24 postoperative hours, the number of emetic episodes was recorded and the subjects rated their nausea on a scale from 0 to 10. Ondansetron-treated subjects had fewer emetic episodes (p less than 0.001) and lower subjective nausea scores (p less than 0.001). The number of complete responders (no emetic episodes and no rescue therapy) was 1 of 24 (4%) and 15 of 26 (58%) in the placebo and ondansetron groups, respectively (p less than 0.001). Ondansetron is clearly more effective than placebo in the prophylaxis of postoperative nausea and vomiting. The adverse event profile for ondansetron was similar to that of placebo.

Dimeric 1,4-dihydropyridines as calcium channel antagonists.

A series of 1,n-alkanediylbis(1,4-dihydropyridines) (n = 2, 4, 6, 8, 10, 12) bridged at C3 of 2,6-dimethyl-3-carboxy-5-carbethoxy-4-(3-nitrophenyl)-1,4-dihydropyridin e were synthesized and evaluated in a radioligand binding assay, [3H]nitrendipine in intestinal smooth muscle, as Ca2+ channel ligands. Binding activity was comparable to that of nitrendipine itself but independent of chain length, suggesting the lack of a major binding contribution by the second 1,4-dihydropyridine group. Analogues lacking the second 1,4-dihydropyridine nucleus or possessing an inactive function (4-nitrophenyl) were no less active, confirming that this series of ligands likely does not bridge adjacent 1,4-dihydropyridine receptors of the Ca2+ channel.

A double-blind, placebo-controlled pilot study examining the effectiveness of intravenous ondansetron in the prevention of postoperative nausea and emesis.

STUDY OBJECTIVE: To compare the efficacy and safety profiles of ondansetron and a placebo when infused immediately prior to anesthesia induction for the prevention of postoperative nausea and emesis (vomiting or retching). DESIGN: Randomized, double-blind, placebo-controlled, parallel, multicenter pilot study. SETTING: Three U.S. ambulatory surgical facilities. PATIENTS: One hundred eighty ASA physical status I and II women scheduled to undergo ambulatory gynecologic surgical procedures while receiving general endotracheal anesthesia. INTERVENTIONS: Ondansetron 8 mg or a placebo (equivalent volume) was given intravenously (IV) prior to anesthesia induction to prevent postoperative nausea and vomiting. MEASUREMENTS AND MAIN RESULTS: For the first 24 hours following emergency from anesthesia, patients were monitored in the postanesthesia care unit by a research observer and at home via telephone contact and diary cards. More patients in the ondansetron group (62%) than in the placebo group (40%) were emesis-free over the 24-hour study period (p = 0.005). Ondansetron also was more efficacious than the placebo over the 24-hour study period when a surgery duration of more than 45 minutes was considered in the analyses. For all patients, regardless of surgery duration, there was a low degree of nausea during the course of the study. In all instances, the degree of nausea was slightly lower for ondansetron-treated patients than for placebo-treated patients; however, in no instances were the differences statistically significant. Ondansetron and placebo had similar safety profiles as established by laboratory test results, vital sign monitoring, and adverse event reporting. CONCLUSION: Ondansetron, infused IV before anesthesia induction, appears to be safe and effective when used in the prevention of postoperative nausea and emesis.

Ondansetron prevents postoperative emesis in male outpatients. S3A-379 Study Group.

STUDY OBJECTIVES: To determine (1) the efficacy and safety of ondansetron in the prevention of postoperative nausea and vomiting (PONV) in male outpatients; (2) prognostic factors for PONV in male outpatients; and (3) patients' perceptions of the debilitating effects of PONV in the ambulatory surgery setting. DESIGN: Prospective, randomized, stratified, double-blind study. SETTING: Multicenter-24 medical centers. PATIENTS: 468 ASA physical status I and II males at least 12 years of age scheduled for general anesthesia. INTERVENTIONS: All patients received intravenous ondansetron 4 mg or placebo prior to undergoing general balanced (opioid) anesthesia. MEASUREMENTS AND MAIN RESULTS: In the postanesthesia care unit (PACU), the number of emetic episodes, vital signs, adverse events, and nausea assessments were recorded by a blinded observer. After discharge, and until the end of the 24-hour study period, patients completed a diary that collected emetic episodes, adverse events, nausea, and pharmacoeconomic data. There were no differences in patient demographics or safety profiles between groups. The number of patients with no emesis and no nausea during the 24-hour study period was significantly greater (p < 0.05) with ondansetron 4 mg compared with placebo. Prognostic factors for an increased likelihood of developing PONV in males included a history of motion sickness or previous PONV, patients undergoing nonorthopedic procedures, and surgeries lasting longer than one hour. Finally, 38% of patients experiencing PONV perceived PONV to be as, or more debilitating than, the aftereffects of surgery itself. CONCLUSIONS: Ondansetron 4 mg was more effective than placebo in preventing PONV in male outpatients. Males at potential risk for developing PONV include: (1) those with a history of motion sickness and/or PONV; (2) patients undergoing nonorthopedic procedures; and (3) procedures lasting longer than one hour. Such patients may benefit from receipt of a prophylactic antiemetic. Postoperative nausea and vomiting has a debilitating effect that can be differentiated by patients from the effects of surgery itself.

A randomized, double-blind pilot study examining the use of intravenous ondansetron in the prevention of postoperative nausea and vomiting in female inpatients.

STUDY OBJECTIVE: To compare the efficacy and safety profiles of intravenous (IV) ondansetron (two 8 mg doses 8 hours apart) and a placebo when used in the prevention of postoperative nausea and emesis (vomiting or retching). DESIGN: Randomized, double-blind, placebo-controlled, parallel, multicenter pilot study. SETTING: Four university hospitals in the United States. PATIENTS: Two hundred seven women scheduled to undergo inpatient surgical procedures during general anesthesia. INTERVENTIONS: Patients were randomized to receive, in a double-blind fashion, either two 8 mg doses of IV ondansetron or a placebo. The first study drug dose was administered before induction of anesthesia; the second dose was given 8 hours later. Each study drug dose was admixed with normal saline to 20 ml and administered IV over 2 to 5 minutes. Vital signs were monitored immediately before and 1 minute after completion of the study drug infusion. MEASUREMENTS AND MAIN RESULTS: For the 24-hour period following operation, 60% of the patients who received ondansetron and 26% of the patients who received the placebo were emesis-free (p < 0.001). Subanalyses based on patients' previous history of general anesthesia indicated that ondansetron was superior to the placebo in preventing emesis regardless of history [66% vs. 33% in patients who had never had general anesthesia or had had no nausea or emesis following previous anesthesia (p = 0.001) and 50% vs. 17% in patients who had nausea or emesis following previous anesthesia (p = 0.005)]. Ondansetron also was superior to the placebo for the prevention of nausea over the 24-hour study period regardless of anesthesia history. Ondansetron was generally well tolerated. The adverse event, vital sign, and clinical laboratory test profiles were similar to those for the placebo. No patient who received ondansetron had untoward changes in central nervous system function, including sedation. CONCLUSIONS: Prophylactic IV ondansetron appears to be safe and causes a significant reduction in the frequency and severity of postoperative nausea and emesis.

Ondansetron, clinical development for postoperative nausea and vomiting: current studies and future directions.

The clinical development of ondansetron for the prevention and treatment of postoperative nausea and vomiting has been progressing for 5 years, and continues as new directions of research are being addressed. Large multicentre studies have demonstrated the efficacy of ondansetron in the prevention and treatment of postoperative nausea and vomiting, but no large comparator studies have been reported. Several studies are now being undertaken to compare ondansetron with other currently used antiemetics such as droperidol and metoclopramide, assessing efficacy, safety, pharmacoeconomic, and quality of life parameters. The majority of studies to date have been performed in gynaecological surgery patients receiving general anaesthesia--a population that experiences a high incidence of postoperative nausea and vomiting. Clinical development of ondansetron is therefore progressing to establish its efficacy in a wider surgical population, including paediatrics, the elderly, non-gynaecological surgery, and as retreatment in patients with failed prophylactic antiemetic therapy.

The effects of the menstrual cycle on the incidence of emesis and efficacy of ondansetron.

Postoperative nausea and vomiting after general anesthesia remains a complex and perturbing phenomenon associated with several factors. In women, the phase of the menstrual cycle as a factor in postoperative nausea and emesis is controversial. This retrospective study was performed to assess the effects of the menstrual cycle and efficacy of the antiemetic ondansetron on postoperative emesis. A total of 1169 ASA grade I-II patients from two double-blind, placebo-controlled studies were enrolled in 18 centers. Patients with irregular cycles or taking estrogens or progesterones were excluded from the analysis, leaving 873 patients eligible for this study. The patients were stratified on the basis of their last menses into four groups: 1) 1-8, 2) 9-16, 3) 17-28, and 4) 29-35 days. All patients received a general anesthetic with endotracheal intubation. Patients received either 1, 4, or 8 mg ondansetron or placebo given intravenously before induction of anesthesia. All patients were studied for a 24-h period. Emesis rates were compared with respect to the phase of the menstrual cycle and between menstruating and nonmenstruating patients. There was no relationship (P = 0.100) between the incidence of emesis and the phase of the menstrual cycle in the group receiving the placebo. There was, however, a significant reduction (P < 0.001) in emesis for the ondansetron-treated patients regardless of the phase of the menstrual cycle. In addition, ondansetron had a similar dose-response curve in both menstruating and nonmenstruating women.

Diffusion of dihydropyridine calcium channel antagonists in cardiac sarcolemmal lipid multibilayers.

A membrane bilayer pathway model has been proposed for the interaction of dihydropyridine (DHP) calcium channel antagonists with receptors in cardiac sarcolemma (Rhodes, D.G., J.G. Sarmiento, and L.G. Herbette. 1985. Mol. Pharmacol. 27:612-623) involving drug partition into the bilayer with subsequent receptor binding mediated (though probably not rate-limited) by diffusion within the bilayer. Recently, we have characterized the partition step, demonstrating that DHPs reside, on a time-average basis, near the bilayer hydrocarbon core/water interface. Drug distribution about this interface may define a plane of local concentration for lateral diffusion within the membrane. The studies presented herein examine the diffusional dynamics of an active rhodamine-labeled DHP and a fluorescent phospholipid analogue (DiIC16) in pure cardiac sarcolemmal lipid multibilayer preparations as a function of bilayer hydration. At maximal bilayer hydration, the drug diffuses over macroscopic distances within the bilayer at a rate identical to that of DiI (D = 3.8 X 10(-8) cm2/s), demonstrating the overall feasibility of the membrane diffusion model. The diffusion coefficients for both drug and lipid decreased substantially as the bilayers were dehydrated. While identical at maximal hydration, drug diffusion was significantly slower than that of DiIC16 in partially dehydrated bilayers, probably reflecting differences in mass distribution of these probes in the bilayer.

Ondansetron does not affect alfentanil-induced ventilatory depression or sedation.

Ondansetron is a selective 5-hydroxytryptamine type 3 receptor antagonist effective as an antiemetic in patients experiencing post-operative or cancer chemotherapy-induced nausea and vomiting. Currently, no information is available regarding the interaction of ondansetron with opioids, although a serotonin antagonist might be expected to modify some opioid actions. This study was designed to measure the effects of ondansetron on alfentanil-induced ventilatory depression and sedation in healthy male volunteers. Ventilatory drive (measured as the end-tidal CO2 necessary to produce a minute ventilation of 15 l/min) was determined in 29 subjects using a modification of the Read rebreathing technique. Sedation was measured by asking the subjects to complete visual analog scales. Alfentanil was administered as a bolus (5 micrograms/kg) followed by a continuous infusion (0.25-0.75 micrograms.kg-1.min-1) for at least 90 min. Study medication (ondansetron 8 or 16 mg or vehicle placebo) was then administered in a randomized, double-blind manner, and the alfentanil was infused for an additional 15 min. Measurements of ventilatory drive and sedation were made at baseline, during alfentanil infusion, after study medication, and at 30-min intervals after alfentanil was discontinued. Alfentanil produced significant ventilatory depression (P less than 0.001) and sedation (P less than 0.001) in all three groups. Neither placebo nor ondansetron produced further change in the intensity of either alfentanil effect. After discontinuation of the opioid, both ventilatory depression and sedation decreased, and the rate of recovery was not significantly different between groups. The data indicate that alfentanil-induced sedation and ventilatory depression are not significantly affected by the subsequent administration of ondansetron.

The clinical development of ondansetron for use in the prevention and treatment of postoperative nausea and vomiting.

An international clinical trial programme has been established to assess the efficacy and safety of ondansetron in the prevention and treatment of postoperative nausea and vomiting. The programme included nine pilot studies and six key placebo-controlled studies. These studies have evaluated both oral and intravenous formulations of ondansetron in the prevention of postoperative nausea and vomiting, and intravenously administered ondansetron in the treatment of established symptoms. Most patients included in the trials were adult women, less than 50 years of age, receiving anaesthesia for gynaecological surgery. The primary efficacy analysis for emesis was based on the assessment of complete response (i.e. absence of emetic episodes or nausea in the first 24 h postoperatively). These trials clearly demonstrated the anti-emetic efficacy of ondansetron in the prevention and treatment of postoperative nausea and vomiting.

Prophylactic intravenous ondansetron in female outpatients undergoing gynaecological surgery: a multicentre dose-comparison study.

The efficacy and safety of prophylactic intravenous ondansetron in preventing postoperative nausea and vomiting was investigated in a randomized, stratified, double-blind, placebo-controlled, dose-comparison study of 580 ASA physical class I and II female outpatients undergoing gynaecological surgery and receiving general anaesthesia. Patients received either ondansetron 1, 4 or 8 mg, or placebo i.v. immediately prior to a standardized technique for induction and maintenance of anaesthesia. All patients were intubated and received nitrous oxide and a narcotic. All doses of ondansetron were significantly more effective than placebo in preventing emesis over the 24 h postoperative period. Ondansetron significantly decreased nausea and emesis scores over 24 h postoperatively without causing sedation. No changes in laboratory parameters (haematology, blood chemistry, and liver enzymes) or vital signs (heart rate, blood pressure, and respiratory rate) were observed. Headache and dizziness were the most common side-effects; however, their incidence was the same as with placebo. Ondansetron was generally well tolerated, as evidenced by an adverse event, laboratory safety, and vital sign profile similar to placebo. Ondansetron 4 mg was found to be the optimal prophylactic i.v. dose for female outpatients over the entire 24 h postoperative period. Higher doses may offer an added benefit in some patients, such as those with a history of nausea and vomiting following general anaesthesia.

Cardiovascular stability with rapid intravenous infusion of ondansetron.

The acute cardiovascular effects of rapid iv administration of the antiemetic ondansetron, a selective serotonin (5-HT3) receptor antagonist were determined in a randomized, blinded, placebo-controlled study. Measurements of heart rate, blood pressure, oxygen saturation and respiratory rate were made preoperatively over a five-minute period which followed a two-minute infusion of the medication. Intraoperative and postoperative data were not collected. None of the variables recorded changed significantly during the infusion or in the observation period which followed. Within the limitations of this study, we detected no cardiovascular change in the five minutes between the end of the drug infusion and the induction of anaesthesia.