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 21, 2025
Marije E. Otto, Katelijne V. van der Heijden, Jan W. Schoones et al.
correction
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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.