What are the pharmacokinetics of hydralazine?

From the Guidelines

Hydralazine's pharmacokinetics are characterized by a rapid onset of action, with blood pressure beginning to decrease within 10-30 minutes, and the effect lasting 2-4 hours, as noted in the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults 1.

Key Pharmacokinetic Properties

• The drug is administered via slow IV infusion, with an initial dose of 10 mg, and can be repeated every 4-6 hours as needed 1.
• Hydralazine's pharmacokinetics are not extensively described in terms of absorption, distribution, metabolism, and excretion in the provided guidelines, but its effects on blood pressure are well-documented 1.

Clinical Considerations

• The unpredictability of response and prolonged duration of action make hydralazine less desirable as a first-line agent for acute treatment in most patients 1.
• However, hydralazine remains a valuable option for the management of hypertensive emergencies, particularly when other agents are contraindicated or ineffective 1.

Important Notes

• The guidelines emphasize the importance of careful patient selection and monitoring when using hydralazine, due to its potential for unpredictable responses and adverse effects 1.
• As with any antihypertensive agent, the goal of therapy is to rapidly and safely reduce blood pressure to prevent target organ damage, while minimizing the risk of adverse effects 1.

From the FDA Drug Label

HydrALAZINE is rapidly absorbed after oral administration, and peak plasma levels are reached at 1 to 2 hours. Plasma levels of apparent hydrALAZINE decline with a half-life of 3 to 7 hours. Binding to human plasma protein is 87%. Plasma levels of hydrALAZINE vary widely among individuals HydrALAZINE is subject to polymorphic acetylation; slow acetylators generally have higher plasma levels of hydrALAZINE and require lower doses to maintain control of blood pressure. HydrALAZINE undergoes extensive hepatic metabolism; it is excreted mainly in the form of metabolites in the urine.

The pharmacokinetics of hydralazine include:

• Absorption: rapid absorption after oral administration
• Peak plasma levels: reached at 1 to 2 hours
• Half-life: 3 to 7 hours
• Protein binding: 87% bound to human plasma protein
• Metabolism: extensive hepatic metabolism
• Excretion: mainly in the form of metabolites in the urine
• Polymorphic acetylation: slow acetylators have higher plasma levels and require lower doses 2

From the Research

Pharmacokinetics of Hydralazine

The pharmacokinetics of hydralazine is a complex process that involves its absorption, distribution, metabolism, and excretion.

• Hydralazine is absorbed well from the gastrointestinal tract 3.
• It has an extensive and complex metabolism that depends on the acetylator status of the individual, with slow acetylators undergoing primary oxidative metabolism and rapid acetylators being acetylated 3, 4.
• The half-lives, clearances, and bioavailability of hydralazine are not significantly altered in congestive heart failure compared to hypertensive patients 3.
• The plasma levels of hydralazine can be affected by the acetylator phenotype, with slow acetylators having higher plasma levels than fast acetylators 4.

Key Pharmacokinetic Parameters

Some key pharmacokinetic parameters of hydralazine include:

• Peak plasma concentrations: lower when measured by a specific assay technique compared to a nonspecific assay technique 5.
• Plasma half-life: shorter when measured by a specific assay technique compared to a nonspecific assay technique, with a mean plasma half-life of 156 minutes for the major metabolite hydralazine pyruvic acid hydrazone 5.
• Urinary clearance: 28 ml/min for the major metabolite hydralazine pyruvic acid hydrazone 5.
• Bioavailability: not significantly altered in congestive heart failure compared to hypertensive patients 3.

Factors Affecting Pharmacokinetics

Several factors can affect the pharmacokinetics of hydralazine, including:

• Acetylator status: slow acetylators have higher plasma levels and longer half-lives than fast acetylators 3, 4.
• Disease state: congestive heart failure and hypertension can affect the pharmacokinetics of hydralazine, although the exact mechanisms are not fully understood 3.
• Dosing schedule: the dose of hydralazine needs to be adjusted for the acetylation status of patients to achieve optimal plasma levels 4.