Contin M, Riva R, Martinelli P, Albani F, Baruzzi A
Institute of Neurology, University of Bologna, Italy.
Eur J Clin Pharmacol. 1991;41(5):463-6. doi: 10.1007/BF00626370.
The influence of age on the kinetics of a standard oral dose of levodopa administered with an inhibitor of peripheral dopa decarboxylase enzymes (benserazide) has been evaluated in 40 patients with Parkinson's disease (age 34-78 y) on chronic therapy. They were divided into 2 groups, on the basis of age below (21 patients, Group A) or above (19 patients, Group B) 65 y. The area under the plasma concentration-time curve (AUC) of levodopa was significantly greater in the older group (547 versus 428 mumol.l-1.min in Group B), coupled with a reduced apparent oral clearance (8.1 versus 10.7 ml.min-1.kg-1) and a longer plasma elimination half-life (67.6 versus 54.6 min). The age of the patients was positively correlated with the AUC of levodopa (r = 0.474) and its plasma elimination half-life (r = 0.391), and was negatively correlated with clearance (r = -0.489). The findings confirm previous data on volunteers that showed a reduction in the systemic clearance of levodopa due to age, which would probably account for the finding of a greater AUC of levodopa in older patients. The observed, age-mediated differences in levodopa pharmacokinetics, albeit statistically significant, were moderate and were likely to be of only minor importance for the dosing schedule.
在40例接受长期治疗的帕金森病患者(年龄34 - 78岁)中,评估了年龄对标准口服剂量左旋多巴与外周多巴脱羧酶抑制剂(苄丝肼)联合用药动力学的影响。根据年龄将他们分为两组,65岁以下组(21例,A组)和65岁以上组(19例,B组)。老年组左旋多巴的血浆浓度 - 时间曲线下面积(AUC)显著更大(B组为547μmol·l-1·min,而A组为428μmol·l-1·min),同时表观口服清除率降低(8.1对10.7 ml·min-1·kg-1),血浆消除半衰期延长(67.6对54.6分钟)。患者年龄与左旋多巴的AUC(r = 0.474)及其血浆消除半衰期(r = 0.391)呈正相关,与清除率呈负相关(r = -0.489)。这些发现证实了先前在志愿者身上得到的数据,即年龄导致左旋多巴全身清除率降低,这可能解释了老年患者中左旋多巴AUC更高的现象。观察到的年龄介导的左旋多巴药代动力学差异虽然具有统计学意义,但程度适中,可能对给药方案的影响较小。