Haloperidol pharmacokinetics

Brockmoller J, Kirchheiner J, Schmider J, et al. The impact of the CYP2D6 polymorphism on haloperidol pharmacokinetics and on the outcome of haloperidol treatment. Clin Pharmacol Ther 2002 72(4) 438-52. 

A placebo-controlled study in 10 patients taking haloperidol found that alosetron 1 mg daily given during weeks 2 and 3 of the 8-week study period caused no change in haloperidol pharmacokinetics. ... 

Chiu et al, 1992 Lin Finder, 1983 Lin et al, 1988b Potkin et al, 1984 Lin etal., 1989 Ruiz et al, 1996 Jann et al, 1989 Jann etal, 1992 Zhang-Wong etal., 1998). The majority of these studies were carried out with haloperidol. A number of studies examined differences between Caucasians and Hispanics, and African Americans and Caucasians (Midha et al., 1988b Midha etal, 1988a Ruiz et al., 1996). In general these studies provided mixed results. Another noteworthy feature of the research literature is that there appear to be no studies that have considered ethnic differences in pharmacokinetics and response for the depot antipsychotics. This may be an artifact of the low levels of depot prescribing found in the US, China, and Japan. 

Clinicians should be aware of a few drug interactions with Zolpidem. Flumazenil acts as an antagonist to the hypnotic effects of zolpidem. There is decreased alertness when zolpidem is combined with cimetidine. There is an increase in anterograde amnesia in volunteers treated with a combination of imipramine and zolpidem. Haloperidol, ranitidine, chlorpromazine, warfarin, and digoxin, along with cimetidine and flumazenil, do not alter the pharmacokinetics of zolpidem (Salva and Costa, 1995). 

Antipsychotics. Clear guidelines for measuring therapeutic serum concentrations of antipsychotics have not yet been established. There may, however, be specific situations in which they may be of value (e.g., monitoring of haloperidol [HPDL] levels might be useful in patients on concurrent carbamazepine therapy because the latter agent can substantially reduce serum HPDL concentrations). These issues are discussed in greater detail in the Pharmacokinetics/Plasma Level section in Chapter 5. 

Clinically, haloperidol decanoate has been administered to hundreds of chronic schizophrenic patients in several open studies to determine its efficacy, pharmacokinetics, safety, and adverse effects. The trials ranged from 4 months to 2 years, with dosages ranging from 25 to 500 mg given once every 4 weeks. The results of these studies have consistently shown that depot haloperidol ... 

When antipsychotics are used in conjunction with a variety of anticonvulsants, their plasma levels may be significantly altered due to pharmacokinetic interactions. For example, when CBZ and haloperidol are coadministered, their interaction may cause a significant decrease in the neuroleptic s serum levels, sometimes resulting in clinical decompensation (516). Conversely, the cessation of CBZ may lead to increased antipsychotic plasma levels. 

Reyntjens AJM, Heykants JJP, Woestenborghs RJH, et al. Pharmacokinetics of haloperidol decanoate. A 2-year follow-up. Int Pharmacopsychiatry 1982 17 238-246. 

GFJ has been shown to increase the exposure of carbamazepine (175), cisapride (176-179), fluvoxamine (184), losartan (188), methadone (189), scopolamine (191), and sertraline (192). However, only the interaction of GFJ with carbamazepine and cisapride seems to be clinically relevant. No alteration in exposure was observed for clozapine (180,181), heophylline (195), halo-peridol (196), and omeprazole (190). Reports of increased pharmacokinetic parameters of clozapine, theophylline, and haloperidol suggest that an interaction is unlikely to be clinically relevant. Contradicting results were reported for itraconazole (185-187), digoxin (75,183), and sildenafil (193,194). An increased effect on concomitant use of diclofenac and GFJ was observed in rats (182). Overall, the clinical relevance for this drug class appears to be low. 

Yasui N, Kondo T, Suzuki A, et al. Lack of significant pharmacokinetic interaction between haloperidol and grapefruit juice. Int Clin Psychopharmacol 1999 14(2) 113-118. 

Zarifian E, Scatton B, Bianchetti G, Cuche H, Loo H, Morselli PL. High doses of haloperidol in schizophrenia. A clinical, biochemical, and pharmacokinetic study. Arch Gen Psychiatry 1982 39(2) 212-5. 

Kudo S, Ishizaki T. Pharmacokinetics of haloperidol an update. Clin Pharmacokinet 1999 37(6) 435-56. 

Desai M, Tanus-Santos JE, Li L, Gorski JC, Arefayene M, Liu Y, Desta Z, Flockhart DA. Pharmacokinetics and QT interval pharmacodynamics of oral haloperidol in poor and extensive metabolizers of CYP2D6. Pharmacogenomics J 2003 3 105-13. 

A thorough review of the pharmacokinetics of haloperidol, with special emphasis on interactions, has been published (1). 

Because of the frequency of co-administration of benzodiazepines with neuroleptic drugs, it is important to consider possible adverse effects that can result from such combinations. In a brief review, emphasis has been placed on pharmacokinetic interactions between neuroleptic drugs and benzodiazepines, as much information on their metabolic pathways is emerging (166). Thus, the enzyme CYP3A4, which plays a dominant role in the metabolism of benzodiazepines, also contributes to the metabolism of clozapine, haloperidol, and quetiapine, and neuroleptic drug plasma concentrations can rise. Intramuscular levomepromazine in combination with an intravenous benzodiazepine has been said to increase the risk of airways obstruction, on the basis of five cases of respiratory impairment the doses of levomepromazine were higher in the five cases that had accompanying airways obstruction than in another 95 patients who did not (167). 

Uematsu, T., Matsuno, H., Sato, H., Hirayama, H., Hasegawa, K., and Nakashima, M., Steady-state pharmacokinetics of haloperidol and reduced haloperidol in schizophrenic patients analysis of factors determining their concentrations in hair,. Pharm. Sci., 81, 1008, 1992. 

Dencker SJ, Gios I, Martensson E, Norden T, Nyberg G, Persson R, Roman G, Stockman 0, Syard KO. A long-term cross-over pharmacokinetic study comparing perphenazine decanoate and haloperidol decanoate in schizophrenic patients. Psychopharmacology (Berl) 1994 114 24-30. 

Isawa S, Murasaki M, Miura S, Yoshioka M, Uchiumi M, Kumagai Y, Aoki S, Hisazumi H, Kudo S. Pharmacokinetic and pharmacodynamic interactions among haloperidol, carteolol hydrochloride and biperiden hydrochloride. Nihon Shinkei Seishin Yakurigaku Zasshi 1999 19(3) 111-18. 

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