Half-Life of Prazosin
The elimination half-life of prazosin is approximately 2 to 3 hours following oral administration. 1
Pharmacokinetic Properties
The FDA-approved drug label clearly states that following oral administration, prazosin reaches peak plasma concentrations at approximately 3 hours, with a plasma half-life of 2 to 3 hours. 1 This short half-life has important clinical implications for dosing frequency and duration of action.
Key Pharmacokinetic Parameters
Absorption: Peak plasma levels occur between 1 and 3 hours after oral administration, with considerable interindividual variation. 2, 3
Bioavailability: Oral bioavailability ranges from 43.5% to 69.3% (mean 56.9%) due to extensive first-pass hepatic metabolism. 2
Protein Binding: Prazosin is highly bound (92-97%) to plasma proteins, specifically albumin and alpha-1-acid glycoprotein. 2, 3
Volume of Distribution: The steady-state volume of distribution is approximately 42.2 ± 8.9 liters. 2
Clearance: Total body clearance is 12.7 ± 1.3 L/h, with plasma clearance around 80 ml/min. 2
Metabolism and Elimination
Hepatic Metabolism: Prazosin undergoes extensive hepatic metabolism, primarily through demethylation and conjugation pathways. 1, 2
Excretion Routes: The drug is excreted mainly via bile and feces, with only 6% excreted unchanged in urine. 2 The two main O-demethylated metabolites are almost completely excreted in bile. 2
Clinical Implications in Special Populations
Renal Impairment
In chronic renal failure, the plasma elimination half-life is prolonged, the plasma free fraction increases, and peak plasma concentrations are higher. 2
Despite these changes, only 6% of prazosin is excreted unchanged in urine, so renal dysfunction has less impact than hepatic dysfunction. 2
Congestive Heart Failure
Prazosin disposition is modified in CHF patients, with increased plasma free fraction and prolonged elimination half-life. 2
Dosage should be titrated cautiously in these patients due to altered pharmacokinetics. 2
Hepatic Impairment
- Given the extensive hepatic metabolism and high first-pass effect, prazosin kinetics are expected to be significantly altered in liver disease, though specific data are limited. 2
Comparison with Related Alpha-Blockers
Terazosin: Has a significantly longer half-life of approximately 12 hours (3-4 times longer than prazosin), allowing once-daily dosing. 4, 5
Prazosin's shorter half-life necessitates multiple daily dosing (typically 2-3 times daily) to maintain therapeutic blood pressure control throughout the day. 2
Important Clinical Considerations
The short 2-3 hour half-life means prazosin requires multiple daily doses for sustained antihypertensive effect. 1, 2
Despite the short half-life, tolerance has not been observed to develop during long-term therapy. 1
The pharmacokinetic data do not fully explain the disappearance of the first-dose hypotensive effect during continued administration, suggesting receptor-level adaptations may occur. 2
Considerable intrasubject consistency exists in pharmacokinetic response despite intersubject variability, meaning individual patients respond consistently to their dosing regimen. 3