Kapetanovic I M, Sweeney D J, Rapoport S I
J Pharmacol Exp Ther. 1982 May;221(2):434-8.
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.
在四个年龄组（3至4个月、11至12个月、23至24个月和32至34个月）的雄性Fischer-344大鼠中研究了氟哌啶醇的生物处置情况。氟哌啶醇通过腹腔注射给予一次大剂量（0.50mg/kg），或通过植入式渗透微型泵在4天内持续给药（0.15mg/天）。采用带氮磷检测器的气相色谱法测定血浆和脑局部区域中氟哌啶醇的浓度。一次大剂量给药后，在较晚时间点血浆和脑浓度显著更高，32至34月龄动物的血浆消除半衰期显著更长，估计的血浆清除率更低，而3至4月龄动物则相反。一次大剂量给药后6小时，血浆和脑局部区域浓度随年龄增加而升高，直至23至24个月。持续输注达到稳态后，血浆和脑浓度也随年龄增加而升高，直至23至24个月。无论是一次大剂量给药还是持续输注后，11至12月龄和23至24月龄动物的脑/血浆浓度比均低于其他年龄组。结果表明，氟哌啶醇表观血浆清除率降低是老年动物血浆和脑氟哌啶醇浓度较高的主要原因，并且血浆浓度并不总是能预测脑浓度。
