van Laar T, Neef C, Danhof M, Roon K I, Roos R A
Department of Neurology, Leiden University Hospital, The Netherlands.
Mov Disord. 1996 Nov;11(6):633-8. doi: 10.1002/mds.870110607.
A new formulation of a sublingual tablet with 10 mg apomorphine was examined in 13 patients with Parkinson's disease. Vitamin C (250 mg) was added sublingually to lower the salivary pH. Four patients received sublingual apomorphine and nine received sublingual apomorphine as well as vitamin C. Subcutaneous apomorphine was given to all patients. The study was designed as a randomized three-way cross-over study. Tmax, Cmax, and bioavailability (F) were determined. Clinical efficacy was assessed by hand-tapping during 30 s, walking time over 25 m, and a 4-point tremor score. The mean Tmax after subcutaneous apomorphine was 14.5 +/- 1.9 min with a mean Cmax of 19.2 +/- 3.8 ng/ml. The mean clearance of all patients was 3.8 +/- 0.6 L/min. The mean Tmax after sublingual apomorphine was 61.1 +/- 6.9 min vs. 61.7 +/- 8.2 min with vitamin C. The mean Cmax was 7.4 +/- 1.0 ng/ml (- vitamin C) vs. 4.3 +/- 1.3 ng/ml (+ vitamin C). These data resulted consequently in a not significantly different mean bioavailability, varying from 17.6% (- vitamin C) to 6.1% (+ vitamin C). The latency of onset of clinical efficacy varied between 25.0 +/- 8.5 min (- vitamin C) and 26.0 +/- 5.3 min (+ vitamin C). The duration of effect was lower (not significantly) when vitamin C was added: 88.0 +/- 12.5 min (- vitamin C) vs. 61.0 +/- 11.9 min (+ vitamin C). These data show that 10 mg apomorphine sublingually was effective in 56% of the patients. The combination with vitamin C did not significantly change the latency of onset or duration of clinical efficacy. Sublingual apomorphine should be considered as an alternative in the treatment of "off"-periods in Parkinson's disease, in particular when patients have the capacity to anticipate their off-periods.
对一种含10毫克阿扑吗啡的舌下片新剂型在13例帕金森病患者中进行了研究。舌下添加250毫克维生素C以降低唾液pH值。4例患者接受舌下阿扑吗啡，9例患者接受舌下阿扑吗啡以及维生素C。所有患者均给予皮下注射阿扑吗啡。该研究设计为随机三交叉研究。测定了达峰时间（Tmax）、峰浓度（Cmax）和生物利用度（F）。通过30秒内的手部敲击、25米以上的步行时间以及4分制震颤评分评估临床疗效。皮下注射阿扑吗啡后的平均Tmax为14.5±1.9分钟，平均Cmax为19.2±3.8纳克/毫升。所有患者的平均清除率为3.8±0.6升/分钟。舌下含服阿扑吗啡后的平均Tmax为61.1±6.9分钟，而加用维生素C时为61.7±8.2分钟。平均Cmax为7.4±1.0纳克/毫升（-维生素C），加用维生素C时为4.3±1.3纳克/毫升。这些数据导致平均生物利用度无显著差异，范围从17.6%（-维生素C）到6.1%（+维生素C）。临床疗效起效潜伏期在25.0±8.5分钟（-维生素C）和26.0±5.3分钟（+维生素C）之间。加用维生素C时作用持续时间较短（无显著差异）：88.0±12.5分钟（-维生素C）对比61.0±11.9分钟（+维生素C）。这些数据表明，56%的患者舌下含服10毫克阿扑吗啡有效。与维生素C联合使用并未显著改变临床疗效的起效潜伏期或持续时间。舌下阿扑吗啡应被视为帕金森病“关”期治疗的一种替代方法，尤其是当患者有能力预测其“关”期时。
