Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Agents stimulating gastro-intestinal motility ATC code: A03FA01 (Propulsives)

Mechanism of action
The action of metoclopramide is closely associated with parasympathetic nervous control of the upper gastro-intestinal tract, where it has the effect of encouraging normal peristaltic action. This provides for a fundamental approach to the control of those conditions where disturbed gastro- intestinal motility is a common underlying factor.
Metoclopramide stimulates activity of the upper gastro-intestinal tract and restores normal co- ordination and tone. Gastric emptying is accelerated and the resting tone of the gastrooesophageal sphincter is increased. Metoclopramide is a dopamine-receptor antagonist with a direct anti-emetic effect on the medullary chemoreceptor trigger zone.

Pharmacokinetic Properties

5.2 Pharmacokinetic properties
Absorption
Metoclopramide is rapidly absorbed from the gastrointestinal tract and undergoes variable first- pass metabolism in the liver.
After intramuscular administration, the relative bioavailability compared to intravenous application is 60 to 100 %. Peak plasma levels are reached within 0.5 to 2 hours.

Distribution:
The distribution volume is 2-3 l/kg; 13-22% is bound to plasma proteins.

Biotransformation:
Metoclopramide is metabolised in the liver.
Elimination
The predominant route of elimination of metoclopramide and its metabolites is via the kidney, both in unchanged form and in sulfate or glucuronide conjugate form. The main metabolite is N- 4 sulfur conjugate.. It crosses the placenta and is excreted in breast milk. The elimination half-life is about 5 to 6 hours, regardless of the route of administration.
Renal impairment
The clearance of metoclopramide is reduced by up to 70% in patients with severe renal impairment, while the plasma elimination half- life is increased (approximately 10 hours for a creatinine clearance of 10-50 mL/minute and 15 hours for a creatinine clearance <10 mL/minute).
Hepatic impairment
In patients with cirrhosis of the liver, accumulation of metoclopramide has been observed, associated with a 50% reduction in plasma clearance.