FORMATION OF REDUCED HALOPERIDOL AFTER INTRAMUSCULAR HALOPERIDOL ADMINISTRATION IN SCHIZOPHRENIC-PATIENTS

The formation of the reduced metabolite of haloperidol - reduced halop eridol (RH) - was evaluated after intramuscular haloperidol injection in 13 chronic schizophrenic patients. After an overnight fast, each pa tient received a 5mg dose. Plasma samples were obtained prior to injec tion and 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 6, 9, 12, 24, 36, 48, 72 and 96 hours postinjection. Plasma haloperidol, RH and homovanillic acid ( HVA) levels were assayed by high performance liquid chromatography wit h electrochemical detection. Plasma haloperidol concentrations were de tectable in each patient at 96 hours postinjection. The mean time to m aximum (t(max)) plasma concentrations was 0.86 hours. A wide interpati ent variability was observed in the pharmacokinetic parameters for the population. RH was detected in only 6 patients. The mean t(max) of RH occurred at 1.37 hours. Although statistically not significant, the m ean volume of distribution of haloperidol patients with RH was slightl y larger compared with patients with only haloperidol (32.89 vs 28.33 L/kg). The mean elimination half-life of haloperidol was longer but al so not statistically significant in the RW/haloperidol patients compar ed with haloperidol only patients (43.03 vs 34.37 hours). Intramuscula r haloperidol injection produced a characteristic decrease in plasma H VA levels with a t(max) at 0.75 hours. Plasma HVA levels remained decr eased and returned to baseline values 12 hours later. Plasma HVA level s were slightly lower in RH/haloperidol patients compared with haloper idol only patients.