Skip to content

Predicting Drug Candidate Victims of Drug-Drug Interactions, using Microdosing

Marie Croft, Brendan J. Keely, Ian D. Morris, Lan Tann, Graham Lappin

Clinical Pharmacokinetics February 16, 2012 DOI: 10.2165/11597070-000000000-00000 (opens in new tab)

Relevant Not relevant

Study at a glance

AI-extracted from the abstract
Characteristics Crossover study Peer reviewed
Population Healthy male volunteers
Interventions Midazolam Tolbutamide Caffeine Fexofenadine Ketoconazole Fluvoxamine
Dose 25 μg each (microdose); ketoconazole 400 mg; fluvoxamine 100 mg
Measures area under the plasma concentration-time curve from time zero to infinity (AUC(∞))
Topics Microdosing
Keywords Microdose Pharmacology Pharmacokinetics Tolbutamide Ketoconazole Drug interaction Fluvoxamine Fexofenadine Pharmacodynamics Insulin Fluoxetine
Citations 42
Key points Microdosing can detect drug-drug interactions, with pharmacokinetic changes consistent with those from therapeutic-dose studies.

Abstract

ObjectiveThe aim of this crossover human male volunteer study was to investigate the utility of microdosing in the investigation of drug-drug interactions.MethodsA mixture of midazolam, tolbutamide, caffeine and fexofenadine were administered as a microdose (25 μg each) before and after administration of a combined pharmacological dose of ketoconazole (400 mg) and fluvoxamine (100 mg) to inhibit P-glycoprotein and metabolism by cytochrome P450 (CYP) 1A2, CYP3A4 and CYP2C9.ResultsWhen administered alone, pharmacokinetics for all four microdosed compounds scaled well with those reported for therapeutic doses and with previously performed microdose studies. The pharmacokinetics of each compound administered as a microdose were significantly altered after the administration of ketoconazole and fluvoxamine, showing statistically significant (p < 0.01) 12.8-, 8.1- and 3.2-fold increases in the area under the plasma concentration-time curve from time zero to infinity (AUC(∞)) for midazolam, caffeine and fexofenadine, respectively. A 1.8-fold increase (not statistically significant) in AUC(∞) was observed for tolbutamide. The changes in pharmacokinetics mediated by ketoconazole and fluvoxamine were quantitatively consistent with previously reported, non-microdose, drug-drug interaction data from studies including the same compounds.ConclusionThe initial data reported here demonstrate the utility of microdosing to investigate the risk of development drugs being victims of drug-drug interactions.

Comparable studies

Other randomized controlled trials on microdosing, most cited first.

Study Year Design Participants
Use of microdosing to predict pharmacokinetics at the therapeutic dose: Experience with 5 drugs Volunteers 2006 Crossover study
Self-blinding citizen science to explore psychedelic microdosing. Participants who microdose psychedelics 2021 Self-blinding citizen science initiative with placebo control n = 191
Microdosing with psilocybin mushrooms: a double-blind placebo-controlled study Individuals starting to microdose with psilocybin mushrooms (Psilocybe cubensis) 2022 Double-blind placebo-controlled experimental design n = 34
Preliminary Report on the Effects of a Low Dose of LSD on Resting-State Amygdala Functional Connectivity. Healthy young adults, 18 to 35 years old 2019 Randomized controlled trial n = 20
Acute Mood-Elevating Properties of Microdosed Lysergic Acid Diethylamide in Healthy Volunteers: A Home-Administered Randomized Controlled Trial. Healthy male volunteers 2023 Randomized controlled trial n = 80

Citations in the library

Cited by 10

and 5 more in the library

Cites 4

Related reading

Explore topics

Microdosing