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在一项双盲、安慰剂对照、交叉研究中,LSD碱和酒石酸盐的绝对口服生物利用度及生物等效性

Absolute Oral Bioavailability and Bioequivalence of LSD Base and Tartrate in a Double-Blind, Placebo-Controlled, Crossover Study.

作者信息

Arikci Denis, Holze Friederike, Mueller Lorenz, Vizeli Patrick, Rudin Deborah, Luethi Dino, Hysek Cedric M, Liechti Matthias E

机构信息

Clinical Pharmacology and Toxicology, Department of Biomedicine, University Hospital Basel, Basel, Switzerland.

Department of Clinical Research, University Hospital Basel, Basel, Switzerland.

出版信息

Clin Pharmacol Ther. 2025 Sep;118(3):735-743. doi: 10.1002/cpt.3726. Epub 2025 May 26.

Abstract

Lysergic acid diethylamide (LSD) is currently being investigated as a potential treatment for psychiatric and neurological disorders. Different LSD formulations (base or tartrate, oral or intravenous) are being used. Unclear is whether LSD base and tartrate pharmacokinetics are equivalent. Additionally, LSD's absolute oral bioavailability is unknown. Therefore, we tested the bioequivalence of different oral LSD base and tartrate formulations and defined LSD's absolute oral bioavailability at a dose of ~80 μg freebase equivalent. We used a randomized, double-blind, placebo-controlled, five-period crossover design in 20 healthy participants to investigate an ethanolic drinking solution of LSD base, a watery drinking solution of LSD tartrate, a rapid dissolvable tablet of LSD base, an intravenous formulation of LSD tartrate, and corresponding placebos. We assessed pharmacokinetic parameters and acute subjective, autonomic, and adverse effects up to 24 hours. All oral formulations were bioequivalent, with the ethanolic base solution as a reference. The area under the concentration-time curve from zero to infinity and maximum plasma concentration were within a 90% confidence interval of 80-125%. The absolute bioavailability of oral LSD was 80% and similar for all tested formulations. Overall, the oral formulations showed comparable pharmacokinetic and pharmacodynamic parameters. Intravenous LSD administration produced higher "any drug effect," "good drug effect," and "ego dissolution" compared with oral LSD tartrate, more "anxiety" compared with all oral formulations, and more "nausea" and "bad drug effect" compared with oral LSD base and tartrate. In conclusion, dosing with LSD base and tartrate can be considered bioequivalent with high and similar oral bioavailability.

摘要

麦角酸二乙酰胺(LSD)目前正作为一种潜在的精神和神经疾病治疗方法进行研究。正在使用不同的LSD制剂(碱或酒石酸盐,口服或静脉注射)。尚不清楚LSD碱和酒石酸盐的药代动力学是否等效。此外,LSD的绝对口服生物利用度未知。因此,我们测试了不同口服LSD碱和酒石酸盐制剂的生物等效性,并确定了在约80μg游离碱当量剂量下LSD的绝对口服生物利用度。我们在20名健康参与者中采用随机、双盲、安慰剂对照、五周期交叉设计,研究LSD碱的乙醇饮用溶液、LSD酒石酸盐的水性饮用溶液、LSD碱的速溶片、LSD酒石酸盐的静脉制剂以及相应的安慰剂。我们评估了长达24小时的药代动力学参数以及急性主观、自主和不良反应。以乙醇碱溶液为参照,所有口服制剂均具有生物等效性。从零到无穷大的浓度-时间曲线下面积和最大血浆浓度在80%-125%的90%置信区间内。口服LSD的绝对生物利用度为80%,所有测试制剂相似。总体而言,口服制剂显示出可比的药代动力学和药效学参数。与口服LSD酒石酸盐相比,静脉注射LSD产生更高的“任何药物效应”、“良好药物效应”和“自我溶解”,与所有口服制剂相比产生更多“焦虑”,与口服LSD碱和酒石酸盐相比产生更多“恶心”和“不良药物效应”。总之,LSD碱和酒石酸盐给药可被认为具有生物等效性,口服生物利用度高且相似。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1efa/12355019/43fb0f75ae41/CPT-118-735-g001.jpg

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