Pharmacokinetic and pharmacodynamic interactions among haloperidol, carteolol hydrochloride and biperiden hydrochloride.
A beta-adrenoceptor blocker and an anticholinergic agent are often prescribed concomitantly for the treatment of neuroleptic-induced akathisia. The aim of this study was to investigate possible pharmacokinetic interactions of neuroleptic haloperidol with the beta-blocker carteolol and the anticholinergic biperiden. In a 5-step, open-labeled, oral single-dose study, eight healthy male volunteers received 2 mg haloperidol, 10 mg carteolol hydrochloride, and 2 mg biperiden hydrochloride: first each drug alone, then a combination of haloperidol and carteolol, and then all three drugs concurrently. Serum concentrations of haloperidol, carteolol, and biperiden were determined up to 24 hr postdosing, and a safety evaluation was conducted throughout the study. Carteolol increased the area under the haloperidol serum concentration-time curve (AUC0-t) 1.4-fold (P = 0.0014) and decreased the serum clearance of haloperidol up to 67% (P = 0.0127). Biperiden reduced the serum haloperidol concentrations increased by the administration of carteolol. No significant changes of the serum pharmacokinetics of carteolol and biperiden were found as a result of any drug combinations. Adverse events of the central nervous system such as sleepiness and changes in pupil size were observed, but all were mild with clinical insignificance.
Isawa
S
S
Department of Psychiatry, Kitasato University School of Medicine, Japan.
Murasaki
M
M
Miura
S
S
Yoshioka
M
M
Uchiumi
M
M
Kumagai
Y
Y
Aoki
S
S
Hisazumi
H
H
Kudo
S
S
D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D000328:Adult; D017109:Akathisia, Drug-Induced / Q000188:drug therapy; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000494:pharmacology*; D001712:Biperiden / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D002354:Carteolol / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D018680:Cholinergic Antagonists / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006220:Haloperidol / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D008297:Male; D011680:Pupil / Q000187:drug effects; D012894:Sleep Stages / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D014150:Antipsychotic Agents; D018680:Cholinergic Antagonists; D001712:Biperiden; D002354:Carteolol; D006220:Haloperidol