Effect of dimeticone and pepsin on the bioavailability of metoclopramide in healthy volunteers.

OBJECTIVE: To assess the effect of dimeticone and pepsin on the bioavailability of metoclopramide (CAS 7232-21-5) in healthy volunteers. METHODS: The study was conducted using a randomized, open, 2-period crossover design. The volunteers received single administration of 7-mg conventional metoclopramide capsule and a formulation containing metoclopramide (7 mg) plus dimeticone (40 mg) and pepsin (50 mg), with a 7-day interval between treatments. Serial blood samples were collected before dosing and during 24 h post-treatment. Plasma metoclopramide concentrations were analyzed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The pharmacokinetics parameters AUC(last) and C(max) were obtained from the metoclopramide plasma concentration vs. time curves. RESULTS: Metoclopramide's association was bioequivalent to conventional capsule; 90% CIs for geometric mean treatment ratios of C(max) [108.0% (90% CI, 100.4-116.3%)], AUC(last) [103.3% (90% CI, 99.5-107.4%)] were within the predefined range. The metoclopramide formulations were well tolerated at the administered doses and no significant adverse reactions were observed. Thus, these results confirm the good bioavailability of metoclopramide in the new formulation and rule out any impaired absorption when the drugs are formulated in combination.

Metoclopramide modifies oral cephalexin pharmacokinetics in dogs.

The purpose of this study was to investigate whether previous administration of metoclopramide affects cephalexin pharmacokinetics after its oral administration in dogs as well as whether these changes impair its predicted clinical efficacy. Six healthy beagle dogs were included in this study. Oral 25 mg/kg cephalexin monohydrate and intravenous 0.5 mg/kg metoclopramide HCl single doses were administered. Each dog received cephalexin or cephalexin following metoclopramide, with a 2-week washout period. Plasma concentrations of cephalexin were determined by microbiological assay. Cephalexin peak plasma concentration and area under the curve from 0 to infinity significantly increased from 18.77+/-2.8 microg/mL and 82.65+/-10.4 microg.h/mL to 21.88+/-0.8 microg/mL and 113.10+/-20.9 microg.h/mL, respectively, after pretreatment with metoclopramide. No differences between treatments were found for other pharmacokinetic parameters. Pharmacokinetic/pharmacodynamic indices calculated for highly susceptible staphylococci were similar for both experiences. Metoclopramide pretreatment may have increased cephalexin absorption by affecting its delivery to the intestine, and/or enhancing intestinal transporter PEPT1 function. Neither difference in the efficacy of cephalexin nor an increase in toxicity is expected as a result of this modification. Consequently, no dose adjustment is required in cephalexin-treated patients pretreated with metoclopramide.

Validated method for determination of bromopride in human plasma by liquid chromatography--electrospray tandem mass spectrometry: application to the bioequivalence study.

A simple, sensitive and specific liquid chromatography-tandem mass spectrometry method for the quantification of bromopride I in human plasma is presented. Sample preparation consisted of the addition of procainamide II as the internal standard, liquid-liquid extraction in alkaline conditions using hexane-ethyl acetate (1 : 1, v/v) as the extracting solvent, followed by centrifugation, evaporation of the solvent and sample reconstitution in acetonitrile. Both I and II (internal standard, IS) were analyzed using a C18 column and the mobile-phase acetonitrile-water (formic acid 0.1%). The eluted compounds were monitored using electrospray tandem mass spectrometry. The analyses were carried out by multiple reaction monitoring (MRM) using the parent-to-daughter combinations of m/z 344.20 > 271.00 and m/z 236.30 > 163.10. The areas of peaks from analyte and IS were used for quantification of I. The achieved limit of quantification was 1.0 ng/ml and the assay exhibited a linear dynamic range of 1-100.0 ng/ml and gave a correlation coefficient (r) of 0.995 or better. Validation results on linearity, specificity, accuracy, precision and stability, as well as application to the analysis of samples taken up to 24 h after oral administration of 10 mg of I in healthy volunteers demonstrated the applicability to bioequivalence studies.

Metoclopramide and domperidone block the antihypertensive effect of bromocriptime in hypertensive patients / Loa bloqueadores metadopramida y domperidona en pacientes hipertensos y el efecto antihipertensivo de la bromocriptina

This study was conduced in normotensive and hypertensive patients at the Vargas Hospital of Caracas. Normotensive subjects received, in a crossover fashion, placebo, metoclopramide or domperidone, 40 mg of each drug daily for one week. The first group of patients under placebo for one(1) week received a single 2.5 mg oral dose bromocriptine (Br). The second group of patients received 30 mg of metoclopramide (MTC) daily (divided in 3 doses) for week. At the end of period a single dose of 2.5 mg of Br was given to each patient . The third group received domperidone (DOMP) during one week at 30 mg/daily dose to eight hypertesive patients and then a single dose of 2.5 mg Br. Cardiovascular and biochemical parameters including arterial pressure, heart rate, plasma renin activity, and plasma aldosterone concentration were evaluated during the 6 hour period before and after the administration of Br. Neither DOMP nor MTC modified significantly blood presure and heart rate in normotensive subjects. Br reduced both systolic and diastolic arterial pressure in hypertensive subjects. The peak of antihypertensive effect appeared 3 hours after drug administration, but reduction of arterial pressure lasted aproximately 6 hours. At the same time Br reduced plasma aldosterone levels and plasma renin activity. MTC and DOMP reversed the antihypertensive effct or Br and its effect on aldosterone levels and plasma renin activity. We conclude from these findings that Br acts as an antihypertensive agent at peripheral and central levels by stimulating DA2 receptors, which are involved in the aldosterone and renin secretion

Effect of metoclopramide on blood pressure during handgrip test in hypertensive patients / Efecto de la metaclopramida sobre la presión sanguinea durante la prueba handgrip en pacientes hypertensivos

Twenty two (22) hypertensive patients were studied during handgrip test before and during metoclopramide treatment. Metoclopamide was intravenously administered at the rate of 7,5 µg/kg/min during a period of 30 min. Two placebo periods before and after metoclopramide infusion were employed. There was an increase of blood pressure and heart rate during handrgrid test; however, metaclopramide decreased blood pressure prior to handgrip test. In labetalol pretreated hypertensive patients (600-800 mg/daily po, during 7 days period), metoclopramide decreased greater blood pressure before and after handgrip test. Postmenopausal women reacted greater that premenopausal women. It appers that premenopausal women exhibit a vasculoprotecting effect during handgrip which should be attributed to estrogen secretion