Durif F, Paire M, Deffond D, Eschalier A, Dordain G, Tournilhac M, Lavarenne J
Clinique Neurologique, Clermont-Ferrand, France.
Clin Neuropharmacol. 1993 Apr;16(2):157-66. doi: 10.1097/00002826-199304000-00008.
Apomorphine was administered sublingually in two single doses (0.3 and 0.6 mg/kg) to seven patients with idiopathic Parkinson's disease (PD) to assess the relation between clinical efficacy, dosage, and pharmacokinetic parameters of apomorphine. On day 1 and day 3, patients were given 0.3 mg/kg and 0.6 mg/kg of apomorphine, respectively (3 mg tablets). Before apomorphine administration and during the following 4 h, motor score was assessed by measuring tremor, akinesia scores, rising from a chair, and walking speed. The delay to turn on was not different between the two doses but after the 0.3 mg/kg dose, only three patients turned on, whereas all the patients treated with 0.6 mg/kg turned on. Apomorphine (0.3 mg/kg) induced a shorter duration of the "on" period than 0.6 mg/kg (0.3 mg/kg: 24.2 +/- 14.6 min; 0.6 mg/kg: 86.7 +/- 14.9 min). The time to obtain the peak plasma concentration (tmax) obtained with the two doses were not different (0.3 mg/kg: 31.5 +/- 3.4 min; 0.6 mg/kg: 38.3 +/- 2.8 min). Peak plasma concentrations (Cmax) and areas under the curve (AUC) were significantly higher after 0.6 mg/kg than 0.3 mg/kg (Cmax: 0.3 mg/kg: 7.5 +/- 3.2 ng/ml; 0.6 mg/kg: 22.7 +/- 3.6 ng/ml; p < 0.01; AUC: 0.3 mg/kg: 929 +/- 109 ng/ml/min; 0.6 mg/kg; 2,277 +/- 209 ng/ml/min; p < 0.01). There was a significant linear correlation between the duration of therapeutic effect, AUC, and Cmax (r = 0.86, p < 0.01 for AUC; r = 0.63, p < 0.05 for Cmax). These results show that sublingual apomorphine could be of interest in the treatment of "off" phases in parkinsonian patients with motor fluctuations.
对7例特发性帕金森病（PD）患者舌下含服阿扑吗啡，分两个单次剂量（0.3和0.6mg/kg），以评估阿扑吗啡的临床疗效、剂量和药代动力学参数之间的关系。在第1天和第3天，患者分别给予0.3mg/kg和0.6mg/kg的阿扑吗啡（3mg片剂）。在给予阿扑吗啡前及随后4小时内，通过测量震颤、运动不能评分、从椅子上起身及步行速度来评估运动评分。两剂量之间的起效延迟无差异，但给予0.3mg/kg剂量后，仅3例患者起效，而所有接受0.6mg/kg治疗的患者均起效。阿扑吗啡（0.3mg/kg）诱导的“开”期持续时间短于0.6mg/kg（0.3mg/kg：24.2±14.6分钟；0.6mg/kg：86.7±14.9分钟）。两剂量达到血浆峰浓度（tmax）的时间无差异（0.3mg/kg：31.5±3.4分钟；0.6mg/kg：38.3±2.8分钟）。0.6mg/kg后的血浆峰浓度（Cmax）和曲线下面积（AUC）显著高于0.3mg/kg（Cmax：0.3mg/kg：7.5±3.2ng/ml；0.6mg/kg：22.7±3.6ng/ml；p<0.01；AUC：0.3mg/kg：929±109ng/ml/min；0.6mg/kg：2277±209ng/ml/min；p<0.01）。治疗效果持续时间、AUC和Cmax之间存在显著的线性相关性（AUC：r=0.86，p<0.01；Cmax：r=0.63，p<0.05）。这些结果表明，舌下含服阿扑吗啡可能对治疗有运动波动的帕金森病患者的“关”期有效。
