Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1      Pharmacodynamic properties
Pharmacotherapeutic group: Alpha and beta blocking agents, ATC code: C07AG01 
Mechanism of action
Labetalol lowers the blood pressure by blocking peripheral arteriolar alpha-adrenoceptors, thus reducing the peripheral resistance, and by concurrent beta-blockade, protects the heart from reflex sympathetic drive that would otherwise occur.

Pharmacodynamic effects
Cardiac output is not significantly reduced at rest or after moderate exercise. Increases in systolic blood pressure during exercise are reduced but corresponding changes in the diastolic pressure are essentially normal. All of these effects would be expected to be benefit for hypertensive patients.

Pharmacokinetic Properties

5.2     Pharmacokinetic properties
Pharmacokinetics
Labetalol chemically consists of four stereoisomers with different pharmacodynamic effects.

Distribution
Approximately 50% of labetalol in the blood is protein bound. Only negligible amounts of labetalol cross the blood brain barrier in animal studies. Labetalol crosses the placental barrier and is secreted in breast milk.

Biotransformation
Labetalol is metabolised mainly through conjugation to inactive glucuronide metabolites.

Elimination
The glucuronide metabolites are excreted both in the urine and via the bile, into the faeces. Less than 5% of the labetalol dose is excreted unchanged in urine and bile. The plasma half-life of labetalol is about 4 h.

Special patient populations

Hepatic Impairment
Labetalol undergoes significant but variable first-pass metabolism when given by the oral route. In a study of 10 patients with histologically proven cirrhosis, exposure to oral labetalol was increased approximately three-fold compared with healthy controls. Inter-subject variability in both patients and controls was high (approximately 2.5-fold). Patients with hepatic impairment may require lower oral doses of labetalol (see section 4.2 Posology and method of administration and section 4.4 Special warnings and precautions for use).