Half-Life of Labetalol
The plasma half-life of labetalol following oral administration is approximately 6 to 8 hours, with steady-state plasma levels reached by the third day of dosing. 1
Pharmacokinetic Parameters
Oral administration half-life: The elimination half-life ranges from 6 to 8 hours after oral dosing, with most studies reporting values between 6.0 and 7.9 hours 1, 2, 3
Intravenous administration half-life: Following IV administration, the half-life is shorter at approximately 3 to 3.5 hours 2
Time to peak plasma concentration: Peak plasma levels occur 1 to 2 hours after oral administration 1, 3
Time to steady state: Steady-state plasma levels are achieved by approximately the third day of repetitive dosing 1
Clinical Implications of Half-Life
Duration of antihypertensive effect: The duration of effect depends on dose, lasting at least 8 hours following single oral doses of 100 mg and more than 12 hours following single oral doses of 300 mg 1
Peak effects timing: The peak effects of single oral doses occur within 2 to 4 hours, with maximum steady-state blood pressure response upon twice-daily dosing occurring within 24 to 72 hours 1
Beta-blocking duration: About 70% of the maximum beta-blocking effect is present for 5 hours after administration of a single 400 mg oral dose, with approximately 40% remaining at 8 hours 1
Special Populations
Hepatic impairment: In patients with decreased hepatic function, the elimination half-life of labetalol is not altered; however, the relative bioavailability is increased due to decreased first-pass metabolism 1
Renal impairment: In patients with decreased renal function, the elimination half-life of labetalol is not altered 1
Age-related changes: Average bioavailability correlates with age, with values of approximately 30% in the 30- to 40-year age group and approximately 65% at 80 years, though this reflects bioavailability rather than half-life changes 2
Metabolism and Elimination
Primary elimination pathway: Labetalol is eliminated mainly through hepatic metabolism with production of biologically inactive glucuronide metabolites, which are excreted in urine and bile 1, 2
First-pass metabolism: Despite complete gastrointestinal absorption, absolute bioavailability is only 25% due to extensive first-pass metabolism 1
Hepatic extraction: Approximately 85% of labetalol in the blood is removed during a single passage through the liver, making its clearance flow-dependent and sensitive to alterations in hepatic blood flow 2