Haloperidol (Haldol®), Serum
| Haloperidol (Haldol®), Serum | | | |
| Number | | 070482 |
| CPT | | 80173 |
| Synonyms | | Haldol® |
| Specimen | | Serum or plasma |
| Volume | | 4 mL |
| Minimum Volume | | 1.6 mL |
| Container | | Red-top tube, lavender-top (EDTA) tube, or green-top (heparin) tube |
| Collection | | Transfer separated serum or plasma to a plastic transport tube. Do not use a gel-barrier tube. The use of gel-barrier tubes is not recommended due to slow absorption of the drug by the gel. Depending on the specimen volume and storage time, the decrease in drug level due to absorption may be clinically significant. |
| Storage Instructions | | Refrigerate |
| Causes for Rejection | | Gel-barrier tube |
| Reference Interval | | Therapeutic: 4-26 ng/mL |
| Critical Values | | Potentially toxic: >50 ng/mL |
| Use | | Half-life is 15-40 hours. Haloperidol is an antipsychotic tranquilizer used to control acute and chronic psychotic disorders, for the control of Tourette syndrome, and for the treatment of severe behavior problems in hyperactive children. Haloperidol is metabolized by dealkalization, oxidation, and conjugation; the hydroxy derivative is active but concentrations are very low. Haloperidol should be monitored to assess and optimize dosing regimens and maintenance therapy since the relationship between dosage and serum levels at steady-state can be highly variable. The drug should also be monitored to assess adverse reactions and changes associated with co-administered drugs. Haloperidol can increase serum tricyclic level, increase the toxicity of lithium, inhibit hypertensive action and antagonize the stimulant effect of amphetamines. |
| Methodology | | Liquid chromatography/mass spectrometry (LC/MS) |
| Additional Information | | Haloperidol is well absorbed orally; however, a first-pass effect results in 60% (range 44% to 74%) oral bioavailability. Time to peak effect after intramuscular and oral administration is 1 and 3 hours, respectively. Volume of distribution is 20 L/kg, and plasma protein binding is 92%. Clearance (11.8±2.9 mL/kg/minute) is greater in children and smokers and is reduced in the elderly. The metabolism of haloperidol involves cleavage by oxidative N-dealkylation to piperidine metabolites and 4-fluorobenzoylpropionic acid; <1% of unchanged haloperidol is excreted in the urine. The mean plasma half-life after oral administration of single doses varies from 14-24 hours. Haloperidol (ketone) also undergoes reversible metabolism to reduced haloperidol (alcohol); the reduced metabolite is much less active than the parent compound. Although the clearance of reduced haloperidol is similar, its Vd and half-life (67±51 hours) are considerably longer. The accumulation and slow reconversion of reduced haloperidol to parent compound increases the apparent plasma elimination half-life of haloperidol (3-10 days) with repeated dosing. Because of the lack of active metabolites, several studies have investigated the relationship between plasma levels and clinical response. Most studies suggest that typical levels vary between 5 and 15-25 ng/mL. Dopamine (D2) receptors in the brain appear to be approximately 90% saturated at plasma concentrations of 15-20 ng/mL. In reviews and a recent study of the dose-response relationship, plasma levels exceeding 15-20 ng/mL were associated with no improvement and possibly decreased efficacy. Concomitant administration of phenytoin, carbamazepine, or phenobarbital decreases the steady-state plasma concentrations of haloperidol; fluoxetine has the opposite effect. The activity of haloperidol decanoate, a depot preparation, depends on the enzymatic hydrolysis of the ester to free haloperidol. Haloperidol decanoate, given once every 3-4 weeks (in amounts approximately 20 times the daily oral maintenance dose of haloperidol), has maintained patients with chronic schizophrenia for over 1 year. Steady-state plasma concentrations of 2-8 ng/mL are reached by the third monthly injection. This long delay may necessitate an intramuscular loading dose and/or supplemental oral medication during the first 2-3 months of therapy. |
| References | | AMA, Division of Drugs and Toxicology, Drug Evaluations Subscription, Chicago, IL: American Medical Association, Winter 1992. Darby JK, Pasta DJ, Dabiri L, et al, “Haloperidol Dose and Blood Level Variability: Toxicity and Interindividual and Intraindividual Variability in the Nonresponder Patient in the Clinical Practice,” J Clin Psychopharmacol, 1995, 15(5):334-40. Davis JM and Chen N, “Dose Response and Dose Equivalence of Antipsychotics,” J Clin Psychopharm, 2004, 24(2):192-208. Volavka J, Czobor P, Nolan K, et al, “Overt Aggression and Psychotic Symptoms in Patients With Schizophrenia Treated With Clozapine, Olanzapine, Risperidone, or Haloperidol,” J Clin Psychopharm, 2004, 24(2):225-8. |
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