Pharmacokinetic and concentration-effect studies with intravenous metoclopramide.

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.