Hydralazine Half-Life

Hydralazine has a plasma half-life of 3 to 7 hours according to FDA labeling. 1

Pharmacokinetic Profile

Hydralazine is rapidly absorbed after oral administration, with peak plasma levels reached at 1-2 hours after ingestion 1
The elimination half-life of hydralazine shows significant variability between individuals, ranging from 3 to 7 hours in patients with normal renal function 1
Hydralazine is subject to polymorphic acetylation, with slow acetylators generally having higher plasma levels and requiring lower doses to maintain blood pressure control 1
The drug undergoes extensive hepatic metabolism and is excreted mainly as metabolites in the urine 1

Renal function significantly impacts hydralazine's half-life, with impaired renal function leading to prolonged elimination 2
In patients with severely impaired renal function (GFR <30 ml/min), the half-life can be significantly extended, with one study reporting a half-life of 15.8 hours in a patient with a GFR of 16 ml/min 2
Acetylator status affects hydralazine bioavailability and plasma levels, with slow acetylators having higher bioavailability (31-39%) compared to fast acetylators (6.6-9.5%) 3
Despite differences in bioavailability, the elimination half-life appears to be phenotype-independent, ranging from 4 to 6 hours in both fast and slow acetylators 3

The American Heart Association notes that hydralazine begins to decrease blood pressure within 10-30 minutes of administration, with effects lasting 2-4 hours 4
Despite its relatively short half-life, the antihypertensive effect of hydralazine may persist longer than would be predicted based on plasma concentrations alone 5
When used for resistant hypertension, hydralazine is typically considered as a fifth-line agent after other medications have failed to achieve blood pressure control 4
Due to its short half-life and pharmacodynamic profile, hydralazine may require multiple daily dosing for optimal blood pressure control 6

Total daily doses of hydralazine should be kept below 150 mg to avoid drug-induced systemic lupus erythematosus 6, 4
Hydralazine causes increased sympathetic tone and sodium retention, necessitating concurrent use with appropriate diuretic and β-blocker therapy 6, 4
The drug's unpredictable response and duration of action make it less desirable as a first-line agent for acute treatment of hypertension in most patients 7
Hydralazine's major plasma metabolite, hydralazine pyruvic acid hydrazone (HPH), has a longer half-life (approximately 156 minutes) than the parent compound and may accumulate in rapid acetylators after repeated dosing 3, 8

Patients with impaired renal function may require dose adjustments due to the potential for drug accumulation 2
Regular monitoring of blood pressure response is essential due to the significant inter-individual variability in hydralazine pharmacokinetics 1, 3
When discontinuing hydralazine, blood pressure may take 30-140 hours to return halfway to baseline values, suggesting a prolonged terminal elimination phase not fully captured by standard half-life measurements 5