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在37例脑囊虫病人中研究了脑脊液(CSF)和血浆内吡喹酮(PZQ)的药代动力学。病人给予PZQ治疗,剂量20mg/kg,q8h,共3天。在第7次给药前和给药后不同时间,用高压液相荧光法检测CSF和血浆的稳态浓度(Css)变化。实验结果用非线性最小二乘法拟合多剂量给药有滞后时间的一房室一级吸收开放模型。表明CSF的实测PZQ浓度约为血浆的29—60%,其差别有统计意义。CSF浓度和治疗期间的中枢神经系统反应无明显关系,后者通常被认为是囊虫死亡对脑膜的炎性反应。CSF和血浆的药代动力学参数如下:t_(1/2)ka分别为0.16和0.06h;t1/2ke分别为8.9和2.9h;稳态峰值时间1.75和1.30h;血浆至脑脊液平均通过时间(MTT)0.3h;稳态平均浓度分别为0.151和0.448μg/ml;AUC分别为1.21和3.59(μg/ml)·h。皮肌囊虫与脑囊虫的疗效差别似乎与上述药代动力学行为有关。文中讨论了合理给药方案问题。
Pharmacokinetics of cerebrospinal fluid (CSF) and plasma praziquantel (PZQ) were studied in 37 patients with neurocysticercosis. Patients given PZQ treatment, dose 20mg / kg, q8h, a total of 3 days. Changes in steady-state concentration (CSF) and plasma concentrations (Css) were measured by high-pressure liquid-phase fluorometry before the seventh administration and at various times after administration. Experimental Results A one-compartment, one-compartment, open-body model with multi-dose administration of lag time was fitted by non-linear least-squares method. The measured PZQ concentration of CSF is about 29-60% of the plasma, the difference was statistically significant. There was no significant relationship between CSF concentration and central nervous system response during treatment, which is generally considered to be an inflammatory response to cerebrospinal fluid death of a cercariae. Pharmacokinetic parameters of CSF and plasma were as follows: t 1/2 (1/2) ka 0.16 and 0.06 h respectively; t1 / 2ke 8.9 and 2.9 h respectively; steady state peak time 1.75 and 1.30 h; mean plasma to cerebrospinal fluid passage time (MTT) for 0.3 h. The average steady-state concentrations were 0.151 and 0.448 μg / ml, respectively. The AUCs were 1.21 and 3.59 (μg / ml) · h, respectively. The differences in the efficacy of dermatomyosas and cysticercosis appear to be related to the pharmacokinetic behavior described above. The article discusses the rational drug delivery program.