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Background and ObjectiveLysergic acid diethylamide (LSD) is used recreationally and in clinical research. The aim of the present study was to characterize the pharmacokinetics and exposure–response relationship of oral LSD.MethodsWe analyzed pharmacokinetic data from two published placebo-controlled, double-blind, cross-over studies using oral administration of LSD 100 and 200 µg in 24 and 16 subjects, respectively. The pharmacokinetics of the 100-µg dose is shown for the first time and data for the 200-µg dose were reanalyzed and included. Plasma concentrations of LSD, subjective effects, and vital signs were repeatedly assessed. Pharmacokinetic parameters were determined using compartmental modeling. Concentration-effect relationships were described using pharmacokinetic-pharmacodynamic modeling.ResultsGeometric mean (95% confidence interval) maximum plasma concentration values of 1.3 (1.2–1.9) and 3.1 (2.6–4.0) ng/mL were reached 1.4 and 1.5 h after administration of 100 and 200 µg LSD, respectively. The plasma half-life was 2.6 h (2.2–3.4 h). The subjective effects lasted (mean ± standard deviation) 8.2 ± 2.1 and 11.6 ± 1.7 h for the 100- and 200-µg LSD doses, respectively. Subjective peak effects were reached 2.8 and 2.5 h after administration of LSD 100 and 200 µg, respectively. A close relationship was observed between the LSD concentration and subjective response within subjects, with moderate counterclockwise hysteresis. Half-maximal effective concentration values were in the range of 1 ng/mL. No correlations were found between plasma LSD concentrations and the effects of LSD across subjects at or near maximum plasma concentration and within dose groups.ConclusionsThe present pharmacokinetic data are important for the evaluation of clinical study findings (e.g., functional magnetic resonance imaging studies) and the interpretation of LSD intoxication. Oral LSD presented dose-proportional pharmacokinetics and first-order elimination up to 12 h. The effects of LSD were related to changes in plasma concentrations over time, with no evidence of acute tolerance.Trial registration: NCT02308969, NCT01878942.Electronic supplementary materialThe online version of this article (doi:10.1007/s40262-017-0513-9) contains supplementary material, which is available to authorized users.

Ivermectin is an endectocide that has been used broadly in single dose community campaigns for the control of onchocerciasis and lymphatic filariasis for more than 30 years. There is now interest in the potential use of ivermectin regimens to reduce malaria transmission, envisaged as community-wide campaigns tailored to transmission patterns and as complement of the local vector control programme. The development of new ivermectin regimens or other novel endectocides will require integrated development of the drug in the context of traditional entomological tools and endpoints. This document examines the main pharmacokinetic and pharmacodynamic parameters of the medicine and their potential influence on its vector control efficacy and safety at population level. This information could be valuable for trial design and clinical development into regulatory and policy pathways.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-017-1801-4) contains supplementary material, which is available to authorized users.