Pharmacokinetic interaction study between ranitidine and metoclopramide.
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The pharmacokinetics of metoclopramide in healthy volunteers was evaluated to determine if previously repeated doses of ranitidine inhibit the metabolism of the gastrointestinal prokinetic drug. Metoclopramide 20 mg (tablets) in combination with ranitidine 150 mg (tablets) were administered to 14 healthy human volunteers in a two treatment study design, separated by 5 days in which the ranitidine alone was administrated in single p.o. doses twice daily. Plasma concentrations of metoclopramide were determined during a 24 hour period following drug administration. Metoclopramide plasma concentrations were determined by a validated RP-HPLC method. Pharmacokinetic parameters were calculated with compartmental and non-compartmental analysis. In the two periods of treatments, the mean peak plasma concentrations Cmax were 44 ng/ml (metoclopramide alone) and 49.2 ng/ml (metoclopramide and ranitidine). The time taken to reach the peak, Tmax, was 1.15 hrs, and 1.21 hrs, respectively. The total areas under the curve (AUC) was 314.3 ng.hr/ml and 354.06 ng.hr/ml, respectively. The half-life (T 1/2) was 5.6 hr and 6.7 hr. A statistically significant difference was observed for both AUC and half-life of metoclopramide when administered alone or after 5 days of treatment with ranitidine. The experimental data proved the pharmacokinetic interaction between ranitidine of metoclopramide, and suggest monitoring adverse effects in patients. (+info)
Parenteral metoclopramide for acute migraine: meta-analysis of randomised controlled trials.
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OBJECTIVE: To assess the evidence from controlled trials on the efficacy and tolerability of parenteral metoclopramide for acute migraine in adults. DATA SOURCES: Cochrane Central Register of Controlled Trials, Medline, Embase, LILACS, CINAHL, conference proceedings, clinical practice guidelines, and other sources. SELECTION CRITERIA: Randomised controlled trials of parenteral metoclopramide for acute migraine in adults. RESULTS: We reviewed 596 potentially relevant abstracts and found 13 eligible trials totalling 655 adults. In studies comparing metoclopramide with placebo, metoclopramide was more likely to provide significant reduction in migraine pain (odds ratio 2.84, 95% confidence interval 1.05 to 7.68). Used as the only agent, metoclopramide showed mixed effectiveness when compared with other single agents. Heterogeneity of studies for combination treatment prevented statistical pooling. Treatments that did include metoclopramide were as, or more, effective than comparison treatments for pain, nausea, and relapse outcomes reported in all studies. CONCLUSIONS: Metoclopramide is an effective treatment for migraine headache and may be effective when combined with other treatments. Given its non-narcotic and antiemetic properties, metoclopramide should be considered a primary agent in the treatment of acute migraines in emergency departments. (+info)
Measuring outpatient outcomes of emesis and nausea management in pregnant women.
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PURPOSE: Nausea and vomiting during pregnancy (NVP) can create a significant clinical, psychological, and economic burden for patients, health care providers, and payers. The purpose of this analysis is to describe the clinical and economic outcomes of patients diagnosed with NVP utilizing an outpatient program of nursing support and pharmacologic treatment with subcutaneous metoclopramide (SMT). DESIGN: Women with singleton gestations who were experiencing NVP and whose physicians prescribed an outpatient program with SMT between January 2000 and February 2002 were identified from a database. METHODOLOGY: Descriptive and statistical methods were used to analyze and report incidence of treatment failure, hospitalization/emergency room (ER) visits, degree of ketonuria, and Pregnancy-Unique Quantification of Emesis and Nausea (PUQE) score at program start/stop. PRINCIPAL FINDINGS: For a treatment duration of 26.9 +/- 20.8 days, 428 women were enrolled for outpatient SMT at 10.9 +/- 3.2 weeks' gestation. Improvement in NVP symptoms was achieved in 382 women with SMT (89.3 percent), while 46 (10.7 percent) required alteration of antiemetic therapy to subcutaneous ondansetron. The PUQE score at the start of SMT was 7.8 +/- 2.9, decreasing to 3.9 +/- 1.7 by therapy completion (P < .001). At treatment initiation, a PUQE score greater than or equal to 7 was reported by 63.1 percent of women versus 9.1 percent at the program's end (P < .001). Patients with ketonuria that was more than or equal to 1+ decreased from 36.2 percent to 1.4 percent (P < .001). The portion of patients with hospital/ER visits decreased from 65.4 percent to 3.3 percent during treatment (P < .001). Oral dietary improvement was noted in 78.7 percent of patients during treatment. CONCLUSION: Outpatient management was effective in controlling NVP and was associated with a reduced need for hospital or emergency room treatment. (+info)
Apomorphine in idiopathic restless legs syndrome: an exploratory study.
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BACKGROUND: Dopaminergic and opioidergic drugs have been found to be effective in patients with restless legs syndrome (RLS). OBJECTIVES: To test the effect of apomorphine--a combined opioidergic and dopaminergic agonist--and subsequent selective antagonism by naloxone and metoclopramide on subjective and objective symptoms in patients with idiopathic RLS. METHODS: Nine patients with RLS were pretreated with oral domperidone for three days. A modified suggested immobilisation test (SIT) was carried out between 8 pm and 1 am under the following conditions of intravenous drug administration: baseline-apomorphine-apomorphine plus naloxone-apomorphine plus metoclopramide. Outcome variables were a visual analogue scale (VAS) of subjective RLS symptoms and EMG documented periodic leg movements while awake (PLMW). RESULTS: Compared with baseline, apomorphine resulted in a rapid and significant improvement in subjective RLS symptoms as measured by VAS (54.5% improvement; p = 0.011), and an almost immediate cessation of PLMW, measured by PLMW index (98.0% improvement; p = 0.012). Neither additional naloxone nor metoclopramide blocked this effect significantly. While given apomorphine with metoclopramide, there was a trend to reappearance of PLMW. CONCLUSIONS: Apomorphine may be an effective treatment for idiopathic RLS. Its effectiveness may reflect both to its dopaminergic and its opioidergic activity, and is not diminished significantly by blocking only one of these pathways. The trend to a worsening of the PLMW index with metoclopramide hints at a primarily dopaminergic effect of apomorphine in idiopathic RLS. (+info)
The influence of codeine, propantheline and metoclopramide on small bowel transit and theophylline absorption from a sustained-release formulation.
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1. The effects of the anticholinergic agent, propantheline, the opiate, codeine, and the prokinetic agent, metoclopramide, on oral-caecal transit time and on the absorption of theophylline from a sustained-release formulation were examined in six healthy male volunteers. 2. A cross-over randomised sequence design was followed, allowing at least 2 weeks interval between studies. On each occasion 500 mg theophylline in a sustained-release formulation was taken simultaneously with 2 g sulphasalazine at zero time. On three of the four occasions one of the following treatments was given concurrently at -0.5 h, +3.5 h, and +7.5 h: 30 mg codeine phosphate, 30 mg propantheline bromide, or 10 mg metoclopramide monohydrochloride. 3. The appearance of sulphapyridine in the plasma was used to assess oral-caecal transit time and the mean fraction absorbed-time profile of theophylline was calculated from serial serum theophylline concentration measurements using the Wagner-Nelson method. 4. Codeine increased the mean (s.d.) oral-caecal time (h) significantly (5.14 +/- 0.94) compared with the control value (3.78 +/- 0.34). Propantheline inhibited peristaltic contractions to such an extent that the oral-caecal transit time in five of the volunteers was between 9 and 25 h, while sulphapyridine appeared in the 9 h serum sample of the sixth. Metoclopramide did not significantly alter the oral-caecal transit time. 5. Despite the observed changes in oral-caecal transit time the rate and extent of theophylline absorption was similar with all regimens. (+info)
Multimodal antiemetic therapy and emetic risk profiling.
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INTRODUCTION: Postoperative nausea and vomiting (PONV) is a common problem with no simple solution. This review highlights factors that are known to increase the risk of PONV. It examines the various data on pharmacological and non-pharmacological methods that have been used to prevent PONV. METHODS: Peer-reviewed journals on the subject were covered. CONCLUSION: Patient, surgical and anaesthetic factors increase the risk of PONV. While patient and surgical factors are understandably difficult to control, a multimodal approach involving both pharmacological and non-pharmacological interventions has been successfully adopted to reduce the incidence of PONV. Various factors have been identified to categorise patients into different profiles to determine their risk of PONV. Perioperative strategies can then be targeted at these patient groups. (+info)
Metoclopramide improves gastric but not gallbladder emptying in cardiac surgery patients with early intragastric enteral feeding: randomized controlled trial.
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AIM: To evaluate the effect of metoclopramide on gastric emptying in coronary artery bypass graft (CABG) surgery patients with early enteral nutrition and to evaluate the effect of metoclopramide on motility of the gallbladder in these patients. METHODS: A prospective, randomized, placebo-controlled, double-blind study of 40 patients treated at cardiosurgical intensive care unit after CABG surgery. The patients were divided into two groups: metoclopramide group (20 patients; age 60-/+9 years; 85% male), and control group (20 patients; age 59-/+8 years; 70% male). In both groups, enteral feeding with isoosmotic enteral formula was initiated by nasogastric tube 18 hours after surgery. After 6 hours, feeding was stopped, and paracetamol solution (1,000 mg) and 10 mg of metoclopramide IV or 2 ml of saline IV were concurrently administered. Blood samples were obtained 15 (t(+15)), 30 (t(+30)), 60 (t(+60)), and 120 (t(+120)) minutes after the administration of paracetamol. Paracetamol absorption was assessed from the plasma paracetamol concentration and the area under the curve (AUC) from 0 to 120 minutes. Sonographic measurement of gallbladder ejection fraction was also performed 15 (t(+15)), 30 (t(+30)), 60 (t(+60)), and 120 (t(+120)) minutes after the administration of paracetamol. RESULTS: The plasma paracetamol concentrations 15, 30, 60, and 120 minutes after the administration of paracetamol were significantly higher in metoclopramide group than in control group: (t(+15)) 5.4-/+2.7 vs 3.3-/+2.5 (Mann-Whitney U test; P=0.017); (t(+30)) 6.7-/+2.4 vs 3.7-/+2.0 (P=0.006); (t(+60)) 7.7-/+2.5 vs 5.1-/+3.2 (P=0.008); (t(+120)) 8.5-/+2.2 vs 5.2-/+2.8 (P=0.005). The AUC value was 34% larger in the metoclopramide group vs control group (574-/+296 vs 429-/+309; P=0.027). There were no significant differences in gallbladder ejection fraction between groups (group metoclopramide vs control group: (t(0)-t(+15)) -2% vs -2%; (t(+15)-t(+30)) 1% vs 4%; (t(+30)-t(+60)) 0% vs -1%; (t(+60)-t(+120)) 1% vs 3%; P=NS). CONCLUSIONS: In CABG surgery patients with early enteral feeding, a single dose of intravenous metoclopramide effectively improves gastric emptying, but does not have any prokinetic effect on gallbladder motility. (+info)
Effect of metoclopramide on gastric fluid volumes in diabetic patients who have fasted before elective surgery.
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BACKGROUND: Diabetes-induced gastroparesis is believed to increase fasting gastric fluid volume before elective surgery. Metoclopramide is routinely administered preoperatively to reduce gastric fluid volume in these patients. This study compared nondiabetic controls to non-insulin-dependent and insulin-dependent diabetics to determine the effect of metoclopramide, administered before surgery, on gastric volumes in patients who fasted before surgery. METHODS: Control and diabetic patients fasted preoperatively before receiving either placebo or 10 mg intravenous metoclopramide 20 min before induction of anesthesia. After intubation, a gastric tube was placed, and stomach contents were aspirated with volumes compared among the groups. RESULTS: Both groups of diabetic patients were older than the control group, and insulin-dependent patients had a higher incidence of comorbidities compared with the non-insulin-dependent group. Fasting blood sugar and hemoglobin A1C values were higher in both insulin-dependent and non-insulin-dependent patients. Gastric fluid volumes were similar in control, non-insulin-dependent, and insulin-dependent patients (8.0 +/- 2.6 vs. 9.6 +/- 4.1 vs. 17.7 +/- 2.5 ml, respectively). In insulin-dependent diabetic patients, metoclopramide decreased gastric volume compared with placebo treatment (17.7 +/- 2.5 vs. 7.8 +/- 2.9 ml; P = 0.027). After stratification, a subpopulation of patients with poorly controlled diabetes, regardless of type, were identified to have increased gastric residual volumes. CONCLUSION: In elective surgical patients who have fasted before surgery, gastric volumes are minimal, even in diabetics with severe neuropathic symptoms. Metoclopramide prophylaxis to reduce gastric volumes seems to be unnecessary unless the patient has a prolonged history of poor blood glucose control. (+info)