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Annals of Palliative Medicine Jan 2019Cancer cachexia (CC) is one of the most distressing syndromes for both patients and their families. CC can have an impact on patient reported quality of life and overall... (Review)
Review
Cancer cachexia (CC) is one of the most distressing syndromes for both patients and their families. CC can have an impact on patient reported quality of life and overall survival. It is often associated with symptoms such as fatigue, depressed mood, early satiety, and anorexia. Prokinetic agents have been found to improve chronic nausea and early satiety associated with CC. Among the prokinetic agents, metoclopramide is one of the best studied medications. The role of the other prokinetic agents, such as domperidone, erythromycin, haloperidol, levosulpiride, tegaserod, cisapride, mosapride, renzapride, and prucalopride is unclear for use in cachectic cancer patients due to their side effect profile and limited efficacy studies in cancer patients. There has been an increased interest in the use of ghrelin-receptor agonists for the treatment of CC. Anamorelin HCl is a highly selective, novel ghrelin receptor agonist. A meta-analysis was conducted of the recent randomized trials using anamorelin (daily dose of 50 and 100 mg daily). Results show that both total body weight and lean body mass were significantly increased from baseline in the anamorelin group. Anamorelin did not improve overall survival or hand grip strength, and there were no significant differences between groups for frequency or severity of any adverse events. In this review, the authors discuss the available evidence for the use of prokinetics such as metoclopramide and ghrelin receptor agonists for the treatment of CC.
Topics: Cachexia; Forecasting; Gastrointestinal Agents; Ghrelin; Humans; Hydrazines; Metoclopramide; Neoplasms; Oligopeptides
PubMed: 30525771
DOI: 10.21037/apm.2018.11.01 -
BMJ Clinical Evidence Oct 2008Gastro-oesophageal regurgitation is considered a problem if it is frequent, persistent, and associated with other symptoms such as increased crying, discomfort with... (Review)
Review
INTRODUCTION
Gastro-oesophageal regurgitation is considered a problem if it is frequent, persistent, and associated with other symptoms such as increased crying, discomfort with regurgitation, and frequent back arching. A cross-sectional survey of parents of 948 infants attending 19 primary care paediatric practices found that regurgitation of at least one episode a day was reported in 51% of infants aged 0-3 months.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatment for symptomatic gastro-oesophageal reflux? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2007 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 27 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: domperidone, feed thickeners in infants, H(2) antagonists, head elevated sleep positioning, left lateral or prone sleep positioning, metoclopramide, proton pump inhibitors, sodium alginate, surgery, soy formula with added fibre, and weight loss.
Topics: Acute Disease; Administration, Oral; Child; Cross-Sectional Studies; Domperidone; Gastroesophageal Reflux; Humans; Incidence; Infant; Metoclopramide; Proton Pump Inhibitors
PubMed: 19445794
DOI: No ID Found -
The Cochrane Database of Systematic... Nov 2010Migraine is a common, disabling condition and a burden for the individual, health services and society. Many sufferers choose not to, or are unable to, seek professional... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Migraine is a common, disabling condition and a burden for the individual, health services and society. Many sufferers choose not to, or are unable to, seek professional help and rely on over-the-counter analgesics. Co-therapy with an antiemetic should help to reduce nausea and vomiting commonly associated with migraine.
OBJECTIVES
To determine the efficacy and tolerability of paracetamol (acetaminophen), alone or in combination with an antiemetic, compared to placebo and other active interventions in the treatment of acute migraine in adults.
SEARCH STRATEGY
We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies through 4 October 2010.
SELECTION CRITERIA
We included randomised, double-blind, placebo- or active-controlled studies using self-administered paracetamol to treat a migraine headache episode, with at least 10 participants per treatment arm.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial quality and extracted data. Numbers of participants achieving each outcome were used to calculate relative risk and numbers needed to treat (NNT) or harm (NNH) compared to placebo or other active treatment.
MAIN RESULTS
Ten studies (2769 participants, 4062 attacks) compared paracetamol 1000 mg, alone or in combination with an antiemetic, with placebo or other active comparators, mainly sumatriptan 100 mg. For all efficacy outcomes paracetamol was superior to placebo, with NNTs of 12, 5.2 and 5.0 for 2-hour pain-free and 1- and 2-hour headache relief, respectively, when medication was taken for moderate to severe pain. Nausea, photophobia and phonophobia were reduced more with paracetamol than with placebo at 2 hours (NNTs of 7 to 11); more individuals were free of any functional disability at 2 hours with paracetamol (NNT 10); and fewer participants needed rescue medication over 6 hours (NNT 6).Paracetamol 1000 mg plus metoclopramide 10 mg was not significantly different from oral sumatriptan 100 mg for 2-hour headache relief; there were no 2-hour pain-free data. There was no significant difference between the paracetamol plus metoclopramide combination and sumatriptan for relief of "light/noise sensitivity" at 2 hours, but slightly more individuals needed rescue medication over 24 hours with the combination therapy (NNT 17).Adverse event rates were similar between paracetamol and placebo, and between paracetamol plus metoclopramide and sumatriptan. No serious adverse events occurred with paracetamol alone, but more "major" adverse events occurred with sumatriptan than with the combination therapy (NNH 32).
AUTHORS' CONCLUSIONS
Paracetamol 1000 mg alone is an effective treatment for acute migraine headaches, and the addition of 10 mg metoclopramide gives short-term efficacy equivalent to oral sumatriptan 100 mg. Adverse events with paracetamol did not differ from placebo; "major" adverse events were slightly more common with sumatriptan than with paracetamol plus metoclopramide.
Topics: Acetaminophen; Adult; Analgesics, Non-Narcotic; Antiemetics; Drug Therapy, Combination; Humans; Hyperacusis; Metoclopramide; Migraine Disorders; Photophobia; Randomized Controlled Trials as Topic; Sumatriptan
PubMed: 21069700
DOI: 10.1002/14651858.CD008040.pub2 -
Health Technology Assessment... Nov 2021Around one-third of pregnant women suffer from moderate to severe nausea and vomiting, causing physical and emotional distress and reducing their quality of life. There... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Around one-third of pregnant women suffer from moderate to severe nausea and vomiting, causing physical and emotional distress and reducing their quality of life. There is no cure for nausea and vomiting in pregnancy. Management focuses on relieving symptoms and preventing morbidity, and often requires antiemetic therapy. National guidelines make recommendations about first-, second- and third-line antiemetic therapies, although care varies in different hospitals and women report feeling unsupported, dissatisfied and depressed.
OBJECTIVES
To determine whether or not, in addition to intravenous rehydration, ondansetron compared with no ondansetron and metoclopramide compared with no metoclopramide reduced the rate of treatment failure up to 10 days after drug initiation; improved symptom severity at 2, 5 and 10 days after drug initiation; improved quality of life at 10 days after drug initiation; and had an acceptable side effect and safety profile. To estimate the incremental cost per treatment failure avoided and the net monetary benefits from the perspectives of the NHS and women.
DESIGN
This was a multicentre, double-dummy, randomised, double-blinded, dummy-controlled 2 × 2 factorial trial (with an internal pilot phase), with qualitative and health economic evaluations.
PARTICIPANTS
Thirty-three patients (who were < 17 weeks pregnant and who attended hospital with nausea and vomiting after little or no improvement with first-line antiemetic medication) who attended 12 secondary care NHS trusts in England, 22 health-care professionals and 21 women participated in the qualitative evaluation.
INTERVENTIONS
Participants were randomly allocated to one of four treatment groups (1 : 1 : 1: 1 ratio): (1) metoclopramide and dummy ondansetron; (2) ondansetron and dummy metoclopramide; (3) metoclopramide and ondansetron; or (4) double dummy. Trial medication was initially given intravenously and then continued orally once women were able to tolerate oral fluids for a maximum of 10 days of treatment.
MAIN OUTCOME MEASURES
The primary end point was the number of participants who experienced treatment failure, which was defined as the need for further treatment because symptoms had worsened between 12 hours and 10 days post treatment. The main economic outcomes were incremental cost per additional successful treatment and incremental net benefit.
RESULTS
Of the 592 patients screened, 122 were considered eligible and 33 were recruited into the internal pilot (metoclopramide and dummy ondansetron, = 8; ondansetron and dummy metoclopramide, = 8; metoclopramide and ondansetron, = 8; double dummy, = 9). Owing to slow recruitment, the trial did not progress beyond the pilot. Fifteen out of 30 evaluable participants experienced treatment failure. No statistical analyses were performed. The main reason for ineligibility was prior treatment with trial drugs, reflecting an unpredicted change in prescribing practice at several points along the care pathway. The qualitative evaluation identified the requirements of the study protocol, in relation to guidelines on anti-sickness drugs, and the diversity of pathways to care as key hurdles to recruitment while the role of research staff was a key enabler. No important adverse events or side effects were reported.
LIMITATIONS
The pilot trial failed to achieve the recruitment target owing to unforeseen changes in the provision of care.
CONCLUSIONS
The trial was unable to provide evidence to support clinician decisions about the best choice of second-line antiemetic for nausea and vomiting in pregnancy.
TRIAL REGISTRATION
Current Controlled Trials ISRCTN16924692 and EudraCT 2017-001651-31.
FUNDING
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 25, No. 63. See the NIHR Journals Library website for further project information.
Topics: Antiemetics; Cost-Benefit Analysis; Female; Humans; Metoclopramide; Nausea; Ondansetron; Pregnancy; Quality of Life; Vomiting
PubMed: 34782054
DOI: 10.3310/hta25630 -
Critical Care (London, England) Sep 2014Regulatory agencies in North America and Europe recently re-evaluated the safety of metoclopramide. This re-evaluation resulted in recommendations and restrictions in... (Review)
Review
Regulatory agencies in North America and Europe recently re-evaluated the safety of metoclopramide. This re-evaluation resulted in recommendations and restrictions in order to minimise the risk of neurological and other adverse reactions associated with the use of metoclopramide. In the ICU, off-label prescription of metoclopramide is common. We have reviewed the evidence for safety, effectiveness and dosing of metoclopramide in critically ill patients. Furthermore, tachyphylaxis is addressed and alternatives are summarised. Finally, recommendations are presented not to abandon use of metoclopramide in ICU patients, because metoclopramide is considered effective in enhancing gastric emptying and facilitating early enteral nutrition.
Topics: Critical Illness; Dose-Response Relationship, Drug; Drug Prescriptions; Humans; Metoclopramide; Nervous System Diseases; Pharmacokinetics; Tachyphylaxis
PubMed: 25672546
DOI: 10.1186/s13054-014-0502-4 -
The Cochrane Database of Systematic... Jan 2015Enteral nutrition by feeding tube is a common and efficient method of providing nutritional support to prevent malnutrition in hospitalised patients who have adequate... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Enteral nutrition by feeding tube is a common and efficient method of providing nutritional support to prevent malnutrition in hospitalised patients who have adequate gastrointestinal function but who are unable to eat. Gastric feeding may be associated with higher rates of food aspiration and pneumonia than post-pyloric naso-enteral tubes. Thus, enteral feeding tubes are placed directly into the small intestine rather than the stomach, and the use of metoclopramide, a prokinetic agent, has been recommended to achieve post-pyloric placement, but its efficacy is controversial. Moreover, metoclopramide may include adverse reactions, which with high doses or prolonged use may be serious and irreversible.
OBJECTIVES
To determine the effect of intravenous metoclopramide on post-pyloric placement of the naso-enteral tube in adults.
SEARCH METHODS
Trials were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 10) which includes the CUGPD group's specialised register of trials, MEDLINE (1996 to 21 October 2014), EMBASE (1988 to 21 October 2014), LILACS (2005 to 21 October 2014) We did not confine our search to English language publications. Searches in all databases were updated originally in January 2005, then in November 2008 and again in October 2014. No new studies were found in 2008 or in 2014.
SELECTION CRITERIA
We selected randomised controlled trials of adults needing enteral nutrition, who received intravenous or intramuscular metoclopramide to aid placement of transpyloric naso-enteral feeding tubes, compared to placebo or no intervention.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by The Cochrane Collaboration. All analyses were performed according to the intention-to-treat method. We present risk ratios (RR) with 95% confidence intervals (CI).
MAIN RESULTS
Four studies, with a total of 204 participants were included and analysed. The trials compared metoclopramide with placebo (two trials) or with no intervention (two trials). Metoclopramide was investigated at doses of 10 mg (two trials) and 20 mg (two trials). There was no statistically significant difference between metoclopramide versus placebo or no intervention administered to promote tube placement (RR 0.82, 95% CI 0.61 to 1.10). Metoclopramide at doses of 10 mg (RR 0.82, 95% CI 0.60 to 1.11) and 20 mg (RR 0.62, 95% CI 0.15 to 2.62) were equally ineffective in facilitating post-pyloric intubation when compared with placebo or no intervention.
AUTHORS' CONCLUSIONS
In this review, we found only four studies that fitted our inclusion criteria. These were small, underpowered studies, in which metoclopramide was given at doses of 10 mg and 20 mg. Our analysis showed that metoclopramide did not assist post-pyloric placement of naso-enteral feeding tubes.Ideally randomised clinical trials should be performed that have a significant sample size, administering metoclopramide against control, however, given the lack of efficacy revealed by this review it is unlikely that further studies will be performed.
Topics: Antiemetics; Duodenum; Enteral Nutrition; Gastric Emptying; Humans; Injections, Intravenous; Intubation, Gastrointestinal; Jejunum; Metoclopramide; Pylorus; Randomized Controlled Trials as Topic
PubMed: 25564770
DOI: 10.1002/14651858.CD003353.pub2 -
The Cochrane Database of Systematic... May 2010Gastro-esophageal reflux (GER) is the refluxing of gastric contents into the esophagus. Fifty per cent of all infants 0 to 3 months regurgitate at least once a day. This... (Review)
Review
BACKGROUND
Gastro-esophageal reflux (GER) is the refluxing of gastric contents into the esophagus. Fifty per cent of all infants 0 to 3 months regurgitate at least once a day. This drops to 5% once infants are 10 to 12 months old. Three per cent of parents of 10 to 12 month old infants view this as a problem.
OBJECTIVES
To investigate the effectiveness of thickened feeds, positioning, and metoclopramide as compared to placebo in improving the outcome of GER in developmentally normal infants aged one month to two years.
SEARCH STRATEGY
Trials were identified by searching Cochrane Central Register of Controlled Trials (The Cochrane Library 2003), MEDLINE (January 1966 to 23 January 2003), EMBASE (January 1985 to 27 January 2003), and reference lists of articles. Searches in all databases were updated in April 2009.
SELECTION CRITERIA
Randomised studies (parallel or cross over) which evaluated thickened feeds, positional alternations or metoclopramide for the treatment of GER in children between the age of one month and two years who were developmentally normal.
DATA COLLECTION AND ANALYSIS
All three reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials.
MAIN RESULTS
Twenty trials involving 771 children met the inclusion criteria: eight dealt with thickened feeds, five with positioning, and seven with metoclopramide. Few comparisons could be made, and so summary measures were often made with two or three studies. Thickened feeds reduce the regurgitation severity score (standardized mean difference (SMD) -0.94;95% confidence interval -1.35 to -0.52), as well as the frequency of emesis (SMD -0.91; confidence interval -1.22 to -0.61). The reflux index was not reduced (weighted mean difference (WMD) 0.48%; 95% confidence interval -3.27 to 4.23). All five positioning studies utilized esophageal pH monitoring as their outcome measure. Elevating the head of the crib for treating reflux in the supine position is not justifiable. The seven metoclopramide studies used a variety of outcomes. Compared to placebo, metoclopramide appears to reduce daily symptoms ( SMD -0.73; 95% confidence interval -1.16 to -0.30), and reduce the reflux index (WMD -2.80%; 95% confidence interval -5.58 to -0.01). It does increase side effects.
AUTHORS' CONCLUSIONS
Thickened feeds are helpful in reducing the symptoms of GER. Elevating the head of the crib in the supine position does not have any effect. Metoclopramide may have some benefit in comparison to placebo in the symptomatic treatment for GER, but that must be weighed against possible side effects. .
Topics: Dopamine Antagonists; Gastroesophageal Reflux; Humans; Infant; Infant Food; Metoclopramide; Posture; Randomized Controlled Trials as Topic
PubMed: 20464724
DOI: 10.1002/14651858.CD003502.pub3 -
The Cochrane Database of Systematic... May 2016Hyperemesis gravidarum is a severe form of nausea and vomiting in pregnancy affecting 0.3% to 1.0% of pregnancies, and is one of the most common indications for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hyperemesis gravidarum is a severe form of nausea and vomiting in pregnancy affecting 0.3% to 1.0% of pregnancies, and is one of the most common indications for hospitalization during pregnancy. While a previous Cochrane review examined interventions for nausea and vomiting in pregnancy, there has not yet been a review examining the interventions for the more severe condition of hyperemesis gravidarum.
OBJECTIVES
To assess the effectiveness and safety, of all interventions for hyperemesis gravidarum in pregnancy up to 20 weeks' gestation.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register and the Cochrane Complementary Medicine Field's Trials Register (20 December 2015) and reference lists of retrieved studies.
SELECTION CRITERIA
Randomized controlled trials of any intervention for hyperemesis gravidarum. Quasi-randomized trials and trials using a cross-over design were not eligible for inclusion.We excluded trials on nausea and vomiting of pregnancy that were not specifically studying the more severe condition of hyperemesis gravidarum.
DATA COLLECTION AND ANALYSIS
Two review authors independently reviewed the eligibility of trials, extracted data and evaluated the risk of bias. Data were checked for accuracy.
MAIN RESULTS
Twenty-five trials (involving 2052 women) met the inclusion criteria but the majority of 18 different comparisons described in the review include data from single studies with small numbers of participants. The comparisons covered a range of interventions including acupressure/acupuncture, outpatient care, intravenous fluids, and various pharmaceutical interventions. The methodological quality of included studies was mixed. For selected important comparisons and outcomes, we graded the quality of the evidence and created 'Summary of findings' tables. For most outcomes the evidence was graded as low or very low quality mainly due to the imprecision of effect estimates. Comparisons included in the 'Summary of findings' tables are described below, the remaining comparisons are described in detail in the main text.No primary outcome data were available when acupuncture was compared with placebo, There was no clear evidence of differences between groups for anxiodepressive symptoms (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.73 to 1.40; one study, 36 women, very low-quality evidence), spontaneous abortion (RR 0.48, 95% CI 0.05 to 5.03; one study, 57 women, low-quality evidence), preterm birth (RR 0.12, 95% CI 0.01 to 2.26; one study, 36 women, low-quality evidence), or perinatal death (RR 0.57, 95% CI 0.04 to 8.30; one study, 36 women, low-quality evidence).There was insufficient evidence to identify clear differences between acupuncture and metoclopramide in a study with 81 participants regarding reduction/cessation in nausea or vomiting (RR 1.40, 95% CI 0.79 to 2.49 and RR 1.51, 95% CI 0.92 to 2.48, respectively; very low-quality evidence).In a study with 92 participants, women taking vitamin B6 had a slightly longer hospital stay compared with placebo (mean difference (MD) 0.80 days, 95% CI 0.08 to 1.52, moderate-quality evidence). There was insufficient evidence to demonstrate a difference in other outcomes including mean number of episodes of emesis (MD 0.50, 95% CI -0.40 to 1.40, low-quality evidence) or side effects.A comparison between metoclopramide and ondansetron identified no clear difference in the severity of nausea or vomiting (MD 1.70, 95% CI -0.15 to 3.55, and MD -0.10, 95% CI -1.63 to 1.43; one study, 83 women, respectively, very low-quality evidence). However, more women taking metoclopramide complained of drowsiness and dry mouth (RR 2.40, 95% CI 1.23 to 4.69, and RR 2.38, 95% CI 1.10 to 5.11, respectively; moderate-quality evidence). There were no clear differences between groups for other side effects.In a single study with 146 participants comparing metoclopramide with promethazine, more women taking promethazine reported drowsiness, dizziness, and dystonia (RR 0.70, 95% CI 0.56 to 0.87, RR 0.48, 95% CI 0.34 to 0.69, and RR 0.31, 95% CI 0.11 to 0.90, respectively, moderate-quality evidence). There were no clear differences between groups for other important outcomes including quality of life and other side effects.In a single trial with 30 women, those receiving ondansetron had no difference in duration of hospital admission compared to those receiving promethazine (MD 0.00, 95% CI -1.39 to 1.39, very low-quality evidence), although there was increased sedation with promethazine (RR 0.06, 95% CI 0.00 to 0.94, low-quality evidence) .Regarding corticosteroids, in a study with 110 participants there was no difference in days of hospital admission compared to placebo (MD -0.30, 95% CI -0.70 to 0.10; very low-quality evidence), but there was a decreased readmission rate (RR 0.69, 95% CI 0.50 to 0.94; four studies, 269 women). For other important outcomes including pregnancy complications, spontaneous abortion, stillbirth and congenital abnormalities, there was insufficient evidence to identify differences between groups (very low-quality evidence for all outcomes). In other single studies there were no clear differences between groups for preterm birth or side effects (very low-quality evidence).For hydrocortisone compared with metoclopramide, no data were available for primary outcomes and there was no difference in the readmission rate (RR 0.08, 95% CI 0.00 to 1.28;one study, 40 women).In a study with 80 women, compared to promethazine, those receiving prednisolone had increased nausea at 48 hours (RR 2.00, 95% CI 1.08 to 3.72; low-quality evidence), but not at 17 days (RR 0.81, 95% CI 0.58 to 1.15, very low-quality evidence). There was no clear difference in the number of episodes of emesis or subjective improvement in nausea/vomiting. There was insufficient evidence to identify differences between groups for stillbirth and neonatal death and preterm birth.
AUTHORS' CONCLUSIONS
On the basis of this review, there is little high-quality and consistent evidence supporting any one intervention, which should be taken into account when making management decisions. There was also very limited reporting on the economic impact of hyperemesis gravidarum and the impact that interventions may have.The limitations in interpreting the results of the included studies highlights the importance of consistency in the definition of hyperemesis gravidarum, the use of validated outcome measures, and the need for larger placebo-controlled trials.
Topics: Acupuncture Therapy; Adrenal Cortex Hormones; Antiemetics; Female; Humans; Hydrocortisone; Hyperemesis Gravidarum; Metoclopramide; Ondansetron; Placebo Effect; Prednisolone; Pregnancy; Promethazine; Pyridoxine
PubMed: 27168518
DOI: 10.1002/14651858.CD010607.pub2 -
Pharmaceutical Research Jan 2021To investigate the role of cation transporters (OCTs, MATEs) in the renal and hepatic disposition of the radiolabeled antiemetic drug [C]metoclopramide in mice with PET.
PURPOSE
To investigate the role of cation transporters (OCTs, MATEs) in the renal and hepatic disposition of the radiolabeled antiemetic drug [C]metoclopramide in mice with PET.
METHODS
PET was performed in wild-type mice after administration of an intravenous microdose (<1 μg) of [C]metoclopramide without and with co-administration of either unlabeled metoclopramide (5 or 10 mg/kg) or the prototypical cation transporter inhibitors cimetidine (150 mg/kg) or sulpiride (25 mg/kg). [C]Metoclopramide PET was also performed in wild-type and Slc22a1/2 mice. Radiolabeled metabolites were measured at 15 min after radiotracer injection and PET data were corrected for radiolabeled metabolites.
RESULTS
[C]Metoclopramide was highly metabolized and [C]metoclopramide-derived radioactivity was excreted into the urine. The different investigated treatments decreased (~2.5-fold) the uptake of [C]metoclopramide from plasma into the kidney and liver, inhibited metabolism and decreased (up to 3.8-fold) urinary excretion, which resulted in increased plasma concentrations of [C]metoclopramide. Kidney and liver uptake were moderately (~1.3-fold) reduced in Slc22a1/2 mice.
CONCLUSIONS
Our results suggest a contribution of OCT1/2 to the kidney and liver uptake and of MATEs to the urinary excretion of [C]metoclopramide in mice. Cation transporters may contribute, next to variability in the activity of metabolizing enzymes, to variability in metoclopramide pharmacokinetics and side effects.
Topics: Animals; Catecholamine Plasma Membrane Transport Proteins; Female; HEK293 Cells; Hepatobiliary Elimination; Humans; Male; Metoclopramide; Mice; Mice, Knockout; Models, Animal; Organic Cation Transporter 2; Renal Elimination
PubMed: 33559045
DOI: 10.1007/s11095-021-03002-2 -
BMJ Open Oct 2022Hiccup is a common disease that not only occurred on adults but also on infants, which can severely do harm to patients' physical and psychological health....
INTRODUCTION
Hiccup is a common disease that not only occurred on adults but also on infants, which can severely do harm to patients' physical and psychological health. Metoclopramide has been reported to have effects on intractable hiccup. However, there is a limited evidence that describes the efficacy and safety of metoclopramide in the treatment of intractable hiccup. The aim of this article is to obtain evidence on the effectiveness and safety of metoclopramide in treating patients with intractable hiccup.
METHODS AND ANALYSIS
We will search the following databases, including PubMed, Cochrane Library, Embase, Web of Science, CBM, Wan-fang, VIP database, CNKI and MEDLINE from their inception to 11 November 2021. All the randomised controlled trials associated with metoclopramide in treating intractable hiccup will be included. Articles screened, selected and extracted will be performed by two researchers independently. The risk of bias will be assessed by using the Cochrane Collaboration. We will carry out the meta-analysis by using RevMan V.5.4 software.
PROSPERO REGISTRATION NUMBER
CRD42021293000.
Topics: Adult; Data Management; Hiccup; Humans; Meta-Analysis as Topic; Metoclopramide; Research Design; Systematic Reviews as Topic; Treatment Outcome
PubMed: 36202584
DOI: 10.1136/bmjopen-2021-059887