Age effects on haloperidol pharmacokinetics in male, Fischer-344 rats.

Biodisposition of haloperidol was examined in male, Fischer-344 rats in four age groups, 3 to 4, 11 to 12, 23 to 24 and 32 to 34 months. Haloperidol was administered i.p. as a bolus (0.50 mg/kg) or continuously during 4 days from an implanted osmotic minipump (0.15 mg/day). Plasma and regional brain concentrations of haloperidol were determined by gas chromatography with a nitrogen-phosphorus detector. After a bolus administration, plasma and brain concentrations were significantly higher at later time points, the plasma elimination half-life was significantly longer and the estimated plasma clearance was lower in 32- to 34- than in 3- to 4-month-old animals. The plasma and regional brain concentrations 6 hr after a bolus increased as a function of age, up to 23 to 24 months. At a steady state after continuous infusion, plasma and brain concentrations also rose with age up to 23 to 24 months. After either bolus or continuous infusion, the brain/plasma concentration ratios were lower at 11- to 12- and 23- to 24-months-of-age than at either of the other age groups. The results indicate that a reduced apparent plasma clearance of haloperidol is primarily responsible for higher plasma and brain concentrations of haloperidol in the older animals and that plasma concentrations are not always predictive of brain concentrations.