What are the pharmacokinetics of Benperidol?

Absorption of Benperidol

Benperidol is well absorbed after oral administration. It undergoes extensive first-pass metabolism in the liver, resulting in low systemic bioavailability of approximately 20-30%. This means that a large portion of an oral dose is metabolized before reaching systemic circulation. Peak plasma concentrations are achieved 3-6 hours after an oral dose.

Distribution of Benperidol

Benperidol is highly protein bound, primarily to albumin, with over 99% bound in plasma. It has a large volume of distribution of 20-30 L/kg, indicating extensive distribution into tissues. Benperidol can cross the blood-brain barrier and placenta, and is also distributed into breast milk.

Metabolism of Benperidol

Benperidol is extensively metabolized in the liver by the cytochrome P450 system, primarily the CYP2D6 isoenzyme. The major metabolites are reduced benperidol, hydroxylated benperidol, and benperidol N-oxide. These metabolites have little to no antipsychotic activity. Benperidol also inhibits some P450 enzymes, which can lead to drug-drug interactions.

Elimination of Benperidol

The elimination half-life of benperidol is 10-30 hours. It is excreted mainly in the urine, with 5-30% excreted unchanged and the remainder as metabolites. Fecal excretion accounts for less than 4% of an administered dose. The clearance of benperidol is decreased in the elderly, patients with hepatic or renal impairment, and P450 inhibitors, requiring dose adjustment or avoidance in these populations.

Dosing of Benperidol

Due to its poor bioavailability and long half-life, benperidol must be dosed 2-3 times daily to achieve sustained therapeutic levels. Typical initial doses for schizophrenia are 2-10 mg orally 2-3 times per day, with gradual titration based on response and tolerability. The maximum recommended dose is 60 mg/day. Benperidol may take 1-2 weeks of continuous treatment to reach steady state, as with other antipsychotics.

Overall, the pharmacokinetic properties of benperidol, including poor oral bioavailability, extensive protein binding, metabolism by P450 enzymes, and long half-life, have important implications for its dosing, administration, and potential drug interactions in clinical use. Careful management and monitoring are required especially when initiating or discontinuing benperidol treatment due to variability between patients and the risk of side effects or withdrawal symptoms.

There are various forms of drugs available, such as tablets or liquids, and each may have a separate patient information leaflet (PIL) for different doses. It is important to refer to the PIL for the specific form and dose of the drug that you have been prescribed.

You can search for further information and PILs on websites such as: