Haloperidol Pharmacokinetics

Haloperidol is an antipsychotic medication that is available as an oral preparation as well as intravenous and intramuscular injections.

The drug has a high protein binding capacity in humans, with around 90% bound to plasma in the blood. The free action is only 7.5% to 11.6%. Haloperidol undergoes extensive metabolism in the liver, with only around 1% of the drug originally administered being excreted in the urine unchanged.

The main mode of hepatic clearance is through glucuronidation, reduction and oxidation mediated by CYP3A4. Excretion is biliary, meaning the drug leaves the body in the feces and urine. The half-life is between 14 and 26 hours for intravenous preparations, 21 hours for intramuscular preparations and between 14 and 37 hours for oral preparations.

Properties

Oral preparations

Oral haloperidol has a bioavailability of between 60% and 70%. However the mean Tmax and T1/2 varies significantly between studies, at 1.7–6.1 hours and 14.5–36.7 hours, respectively.

Intramuscular preparations

One injectable preparation is the long-acting decanoate ester which is used to treat schizophrenia and related conditions in patients who have had difficulty adhering to other medication plans. This can happen if patients have a poor understanding of their illness or because they forget to take their tablets. Patients are administered an injection once every four weeks. Haloperidol decanoate must only be administered intramuscularly and is not for intravenous use. The drug is quickly absorbed and has a high bioavailability. In healthy individuals, the Tmax is around 20 minutes, while it is 33.8 minutes in people with schizophrenia. The T1/2 is just under 21 hours. The blood plasma haloperidol level reaches peak concentration at around six days post-administration and the half-life is approximately six weeks.

Intravenous injection

When administered intravenously, haloperidol has a bioavailability of 100%. The onset of action occurs within seconds and lasts for around four to six hours. The T1/2 is just over 26 hours. A slow IV infusion can be given if a slower onset and longer duration of action are required.

Therapeutic doses

For therapeutic action, the plasma level of haloperidol needs to be between 4 and 25 micrograms per liter. Plasma levels should be monitored to determine dose adjustments and to assess compliance. If the blood plasma level exceeds the recommended therapeutic range, the patient is at risk of side effects and even haloperidol intoxication.