Epidemiologic investigation of the relative clearance of haloperidol by mixed-effect modeling using routine clinical pharmacokinetic data in Japanese patients

Eiji Yukawa, Tsuyoshi Hokazono, Akiko Funakoshi, Miho Yukawa, Shigehiro Ohdo, Shun Higuchi, Ritsuko Ichimaru, Takako Maki, Kanemitsu Matsunaga, Motoaki Anai, Yoshinobu Goto

Research output: Contribution to journalArticle

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Abstract

The steady-state trough concentrations of haloperidol were studied to clarify the role of the characteristics of Japanese patients in estimating haloperidol dosing regimens by using routine therapeutic drug-monitoring data. Nonlinear mixed-effects modeling (NONMEM) was used to estimate the effect of a variety of developmental and demographic factors on haloperidol clearance values using 270 serum level measurements obtained from 191 patients during their clinical course. The final model describing haloperidol's relative clearance was CL = 0.74 · TBW0.594 · DOSE0.326 · 1.32(CO1) · 0.867(AGE), where CL is clearance (measured in liters per hour), TBW is the total body weight (in kilograms), DOSE is the daily dose of haloperidol (in grams per kilogram per day), CO1 = 1 for concomitant administration of antiepileptic drugs (phenobarbital, phenytoin, or carbamazepine) and CO1 = 0 otherwise, and AGE = 1 for patients aged 55 years or older and AGE = 0 otherwise. Concomitant administration of haloperidol and antiepileptic drugs resulted in a 32% increase in haloperidol clearance. Patients aged 55 years or older showed a 13.3% reduction in clearance values compared with the younger population.

Original languageEnglish
Pages (from-to)685-690
Number of pages6
JournalJournal of Clinical Psychopharmacology
Volume20
Issue number6
DOIs
Publication statusPublished - Dec 10 2000

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Haloperidol
Pharmacokinetics
Anticonvulsants
Drug Monitoring
Carbamazepine
Phenytoin
Phenobarbital
Body Weight
Demography
Serum
Population

All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this

Epidemiologic investigation of the relative clearance of haloperidol by mixed-effect modeling using routine clinical pharmacokinetic data in Japanese patients. / Yukawa, Eiji; Hokazono, Tsuyoshi; Funakoshi, Akiko; Yukawa, Miho; Ohdo, Shigehiro; Higuchi, Shun; Ichimaru, Ritsuko; Maki, Takako; Matsunaga, Kanemitsu; Anai, Motoaki; Goto, Yoshinobu.

In: Journal of Clinical Psychopharmacology, Vol. 20, No. 6, 10.12.2000, p. 685-690.

Research output: Contribution to journalArticle

Yukawa, Eiji ; Hokazono, Tsuyoshi ; Funakoshi, Akiko ; Yukawa, Miho ; Ohdo, Shigehiro ; Higuchi, Shun ; Ichimaru, Ritsuko ; Maki, Takako ; Matsunaga, Kanemitsu ; Anai, Motoaki ; Goto, Yoshinobu. / Epidemiologic investigation of the relative clearance of haloperidol by mixed-effect modeling using routine clinical pharmacokinetic data in Japanese patients. In: Journal of Clinical Psychopharmacology. 2000 ; Vol. 20, No. 6. pp. 685-690.
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