Clinical Pharmacokinetics
March 28, 2017
Randall Brown, Christopher R. Nicholas, Nicholas V. Cozzi et al.
189 citations
Psilocybin is a psychedelic tryptamine being studied for depression and substance use disorders. In an open-label study of 12 healthy adults, escalating oral doses of 0.3, 0.45, and 0.6 mg/kg were given at monthly intervals. No psilocybin was found in plasma or urine; its active metabolite psilocin had an elimination half-life of 3 hours (standard deviation 1.1). Renal clearance of intact psilocin accounted for less than 2% of total clearance, indicating no dose reduction is needed for mild-moderate renal impairment. Body weight did not predict variation in psilocin clearance. No serious adverse events occurred. A fixed 25 mg dose approximates the exposure of a 0.3 mg/kg dose.
Clinical Pharmacokinetics
February 14, 2017
Patrick C. Dolder, Yasmin Schmid, Andrea E. Steuer et al.
134 citations
After oral administration, lysergic acid diethylamide (LSD) reaches peak plasma concentrations of 1.3 ng/mL (100 µg dose) and 3.1 ng/mL (200 µg dose) within about 1.5 hours, with a plasma half-life of 2.6 hours. Subjective effects last 8 to 12 hours depending on dose, and peak effects occur around 2.5 to 2.8 hours after ingestion. A close relationship exists between LSD concentration and subjective response within individuals, but no correlation was found between plasma levels and effects across different people at peak concentration. The effects are related to changing plasma concentrations over time, without evidence of acute tolerance.
Clinical Pharmacokinetics
February 16, 2012
Marie Croft, Brendan J. Keely, Ian D. Morris et al.
42 citations
A crossover study in healthy male volunteers tested whether microdosing (25 μg each of midazolam, tolbutamide, caffeine, and fexofenadine) can detect drug-drug interactions. After administering pharmacological doses of ketoconazole (400 mg) and fluvoxamine (100 mg) to inhibit key metabolic enzymes and transporters, the microdosed compounds showed significant pharmacokinetic changes: area under the curve increased 12.8-fold for midazolam, 8.1-fold for caffeine, and 3.2-fold for fexofenadine (all p < 0.01), and 1.8-fold (not significant) for tolbutamide. These changes matched those reported in conventional drug-drug interaction studies, demonstrating microdosing's utility for assessing whether development drugs are victims of interactions.
Clinical Pharmacokinetics
January 1, 2025
Marije E. Otto, Katelijne V. van der Heijden, Jan W. Schoones et al.
20 citations
The pharmacokinetic parameters of psilocin are consistent across different studies. This finding may help guide the further clinical development of psilocybin-based therapies.
Clinical Pharmacokinetics
February 1, 2025
K V van der Heijden, M E Otto, J W Schoones et al.
7 citations
A systematic review of 13 publications covering eight datasets found that the pharmacokinetics of DMT in humans have been characterized only to a limited extent. All studies administered DMT intravenously except one intramuscular injection. DMT is rapidly metabolized to indole-3-acetic acid (IAA), with a half-life of 4.8–19.0 minutes and clearance of 8.1–46.8 L/min. It shows extensive tissue redistribution, indicated by a high terminal volume of distribution (123–1084 L). High variability in dose-normalized exposure and differences between bolus and infusion administration were observed. Publications often lack details on demographics, absolute doses, and pharmacokinetic parameters, highlighting the need for further studies.
Clinical Pharmacokinetics
July 14, 2025
Lorenz Mueller, Aaron Klaiber, Laura Ley et al.
4 citations
Mescaline, a classic psychedelic, shows dose-proportional increases in blood concentration and effects after oral administration. Peak levels occur within about 2 hours, with a half-life of 3.5 hours. Effects begin around 1 hour after dosing, with intensity and duration increasing from 13% and 2.8 hours at 100 mg to 89% and 15 hours at 800 mg. About 53% of the dose is excreted unchanged in urine, and 31% as a main metabolite. Oral bioavailability is at least 53%, limited by first-pass metabolism, with renal elimination as the primary clearance route.
Clinical Pharmacokinetics
February 21, 2025
Marije E. Otto, Katelijne V. van der Heijden, Jan W. Schoones et al.
correction
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Clinical Pharmacokinetics
November 1, 2025
Léa Comin, Solène Marie, Moreno Ursino et al.
A pharmacokinetic model built from whole-body dynamic PET scans after a microdose of radiolabeled glyburide in 16 healthy people describes the drug's biodistribution and yields parameters consistent with standard blood-based studies. The model included seven compartments, with two each for liver and kidneys. Rifampicin, a drug that can cause interactions, decreased liver distribution by 261%. The estimated central volume of distribution (3.6 L) and elimination rate (0.8 h-1) matched known glyburide pharmacokinetics, suggesting microdose PET data can be used to study whole-body drug distribution.
Clinical Pharmacokinetics
January 7, 2022
Z. Oesterreicher, Sabine Eberl, B. Wulkersdorfer et al.
A single intravenous microdose of radiolabeled ciprofloxacin (1.1 µg) can accurately predict the drug's pharmacokinetics in plasma and subcutaneous tissue but not in epithelial lining fluid. Healthy volunteers received the microdose either with or without a prior therapeutic dose (400 mg). The dose-adjusted area under the concentration–time curve in plasma and subcutaneous tissue was similar between the microdose and therapeutic dose, with ratios within 0.8 to 1.1. Penetration into subcutaneous tissue was comparable across conditions, with tissue-to-plasma ratios of 0.44, 0.44, and 0.38. However, microdose penetration into epithelial lining fluid was highly variable and did not predict therapeutic-dose penetration. Microdosing with microdialysis may aid antimicrobial drug development but requires further study for pulmonary assessments.