Pharmacokinetic and concentration‐effect studies with intravenous metoclopramide.

Abstract

1 Pharmacokinetic and concentration‐effect studies have been carried out following intravenous injection of 10 mg metoclopramide hydrochloride to seven normal male volunteers. 2 It is proposed that a two‐compartment model adequately describes the disposition of the drug which is rapidly distributed (T1/2alpha = 4.9 +/‐ 1.1 min) and eliminated (T1/2beta = 165.7 +/‐ 20.2 min). Total body plasma clearance of the drug is high (10.9 +/‐ 1.5 ml min‐1 kg‐1) and approximates to liver plasma flow. 3 Metoclopramide i.v. increases gastric emptying as measured by an ethanol absorption test (P less than 0.005). The duration of this effect is at least 3 h. 4 Ethanol given after i.v. metoclopramide administration produces significant sedation during the first hour and at 3 h (P less than 0.001). 5 The effect of metoclopramide on gastric emptying, and the degree of sedation induced by ethanol would appear to be related to plasma metoclopramide concentration. 6 Metoclopramide increases serum prolactin to 59 +/‐ 5.8 microgram/1 at 30 min after injection. There is a linear relationship (r = 0.809) between serum prolactin increase and plasma metoclopramide concentration.

Preliminary studies of the pharmacokinetics and pharmacodynamics of prochlorperazine in healthy volunteers.

“…In studies of metoclopramide kinetics in normal volunteers, akathisia was common after i.v. dosing and was occasionally severe (Bateman et al, 1978;Graffner et al, 1979). In patients receiving metoclopramide akathisia is less often reported, even after high doses (Gralla, 1983), though this may be because investigators often do not specifically question patients about such symptoms.…”

The pharmacokinetics of metoclopramide in man with observations in the dog.

“…Urine volumes were recorded and 20 ml aliquots stored deep frozen. Metoclopramide in urine was measured by GC-MS following the addition of deuterated metoclopramide to a concentration of 15 pg/ml (Bateman, Kahn, Mashiter & Davies, 1978).…”

Dystonic reactions and the pharmacokinetics of metoclopramide in children.

“…In adults the plasma decline of metoclopramide is best described by a bi-exponential equation (Bateman et al, 1978). The alpha (distribution) phase is rapid (t½ 4.1 + 2.7 min) and the kinetic parameters derived (©) 1983 Blackwell Scientific Publications from the f8 elimination phase are thus an appropriate approximation of the distribution and elimination of the drug.…”

“…In adults given standard therapeutic doses, metoclopramide undergoes dose dependent kinetics, and the bioavailability of oral metoclopramide is very variable between 30 and 95% (Bateman et al, 1978;Graffner etal., 1979).…”