Gijsman Harm J, van Gerven Joop M A, de Kam Marieke L, Schoemaker Rik C, Pieters Monique S M, Weemaes Margo, de Rijk Roel, van der Post Jeroen, Cohen Adam F
Centre for Human Drug Research, Department of Clinical Pharmacology, Leiden University, Leiden, The Netherlands.
J Clin Psychopharmacol. 2002 Apr;22(2):183-9. doi: 10.1097/00004714-200204000-00012.
Single-dose administration of 5-hydroxytryptophan (5-HTP) is regularly used as a challenge test of the serotonergic system. The use of 5-HTP has been limited by an apparent small window between the occurrence of neuroendocrine endpoints and the occurrence of side effects. Therefore, many dosing strategies have been tried with and without concurrent administration of carbidopa, a peripheral inhibitor of the decarboxylation from 5-HTP to serotonin. The aim of the current study was to assess the relation between pharmacokinetics and pharmacodynamics of 5-HTP. Twelve healthy male volunteers were included in a placebo-controlled, randomized, four-way crossover, double-blind, single-dose investigation of oral 5-HTP with or without coadministration of carbidopa. The four dose regimens were placebo, 5-HTP 100 mg, 5-HTP 200 mg, and 5-HTP 100 mg with coadministration of carbidopa 100 mg and 50 mg at 3 hours before and 3 hours after the administration of 5-HTP, respectively. The last regimen resulted in a doubling of the elimination half-life, an apparent clearance at least 14 times smaller, and a 15.4 times greater area under the curve compared with 5-HTP 100 mg without carbidopa. Furthermore, it was the only regimen to induce a significant change in cortisol and prolactin. It did not induce any change in subjective psychologic symptoms or cardiovascular parameters, but it was the only regimen to induce some nausea in three participants. The authors conclude that this regimen of 5-HTP 100 mg plus carbidopa is a relatively simple, effective, and tolerable challenge of the presynaptic serotonergic system. Further increase of the dose of 5-HTP might improve the size of the effect on endpoints as long as the tolerability remains good.
单剂量服用5-羟色氨酸（5-HTP）常用于血清素能系统的激发试验。5-HTP的使用受到限制，因为神经内分泌终点出现与副作用出现之间的时间窗似乎很窄。因此，人们尝试了多种给药策略，包括同时或不同时服用卡比多巴（一种将5-HTP脱羧转化为血清素的外周抑制剂）。本研究的目的是评估5-HTP的药代动力学和药效学之间的关系。12名健康男性志愿者参与了一项安慰剂对照、随机、四交叉、双盲、单剂量口服5-HTP的研究，研究中5-HTP单独服用或与卡比多巴联合服用。四种给药方案分别为安慰剂、5-HTP 100mg、5-HTP 200mg，以及5-HTP 100mg联合卡比多巴100mg（5-HTP给药前3小时服用）和50mg（5-HTP给药后3小时服用）。与单独服用5-HTP 100mg相比，最后一种给药方案使消除半衰期延长了一倍，表观清除率至少降低了14倍，曲线下面积增大了15.4倍。此外，这是唯一能引起皮质醇和催乳素显著变化的给药方案。它没有引起主观心理症状或心血管参数的任何变化，但却是唯一在三名参与者中引起一些恶心的给药方案。作者得出结论，5-HTP 100mg加卡比多巴的这种给药方案是对突触前血清素能系统相对简单、有效且耐受性良好的激发试验。只要耐受性良好，进一步增加5-HTP剂量可能会改善对终点指标的影响程度。
