Laslo Amanda M, Eastwood James D, Urquhart Brad, Lee Ting-Yim, Freeman Dave
Department of Medical Biophysics, University of Western Ontario, London, Ont., Canada.
J Neurosci Methods. 2004 Oct 30;139(2):195-201. doi: 10.1016/j.jneumeth.2004.04.030.
We compared subcutaneous and oral methods of nimodipine administration to determine a method of nimodipine administration that maintained serum levels at or above the optimal therapeutic concentration (7 ng/ml). Plasma concentrations of nimodipine were measured in New Zealand White rabbits (2.6-3.9 kg). First, peak plasma concentration (C(max)), time to reach peak plasma concentration (T(max)), and area under the curve (AUC) parameters were calculated and compared between animals receiving oral or subcutaneous nimodipine (5-15 mg/kg). Next, plasma concentrations were measured 24 h after subcutaneous administration of 2.5 mg/kg of nimodipine in healthy animals and animals with experimentally induced SAH. C(max), T(max) and AUC parameters were significantly greater for subcutaneous compared to oral nimodipine administration, irrespective of dose. Mean nimodipine concentrations at 24 h were >7 ng/ml in both healthy animals (12.9 +/- 10.0 ng/ml) and in animals with SAH (11.8 +/- 4.6 ng/ml) that received 2.5 mg/kg of subcutaneous nimodipine. In this model, the subcutaneous method of nimodipine administration consistently maintains plasma levels at or above the optimal therapeutic concentration, whereas oral administration fails to do so.
我们比较了尼莫地平的皮下给药和口服给药方法，以确定一种能使血清水平维持在最佳治疗浓度（7纳克/毫升）或以上的尼莫地平给药方法。在新西兰白兔（体重2.6 - 3.9千克）中测量了尼莫地平的血浆浓度。首先，计算并比较了口服或皮下给予尼莫地平（5 - 15毫克/千克）的动物的血浆峰浓度（C(max)）、达到血浆峰浓度的时间（T(max)）和曲线下面积（AUC）参数。接下来，在健康动物和实验性诱导蛛网膜下腔出血（SAH）的动物皮下注射2.5毫克/千克尼莫地平24小时后测量血浆浓度。无论剂量如何，皮下给予尼莫地平的C(max)、T(max)和AUC参数均显著高于口服给药。接受2.5毫克/千克皮下尼莫地平的健康动物（12.9±10.0纳克/毫升）和SAH动物（11.8±4.6纳克/毫升）在24小时时的平均尼莫地平浓度均>7纳克/毫升。在该模型中，尼莫地平的皮下给药方法始终能使血浆水平维持在最佳治疗浓度或以上，而口服给药则无法做到。
