ArticleBritish journal of clinical pharmacology2015
Midazolam microdose to determine systemic and pre-systemic metabolic CYP3A activity in humans.
Article in British journal of clinical pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Altered Bioavailability and Pharmacokinetics in Crohn's Disease: Capturing Systems Parameters for PBPK to Assist with Predicting the Fate of Orally Administered Drugs.Clinical pharmacokinetics · 2022Pooled it
- Oral bioavailability of microdoses and therapeutic doses of midazolam as a 2-dimensionally printed orodispersible film in healthy volunteers.European journal of clinical pharmacology · 2022Trial
- Midazolam Pharmacokinetics in Obese and Non-obese Children and Adolescents.Clinical pharmacokinetics · 2020Trial
- Minor contribution of cytochrome P450 3A activity on fentanyl exposure in palliative care cancer patients.Scientific reports · 2019Trial
- Microdosed Cocktail of Three Oral Factor Xa Inhibitors to Evaluate Drug-Drug Interactions with Potential Perpetrator Drugs.Clinical pharmacokinetics · 2019Trial
- Identification of the caffeine to trimethyluric acid ratio as a dietary biomarker to characterise variability in cytochrome P450 3A activity.European journal of clinical pharmacology · 2019Trial
- A Two-way Randomized Cross-over Pharmacokinetic and Pharmacodynamic Study of an Innovative Oral Solution of Midazolam (ADV6209).Pharmaceutical research · 2017Trial
- Dose-Dependent Bioavailability and CYP3A Inhibition Contribute to Non-Linear Pharmacokinetics of Voriconazole.Clinical pharmacokinetics · 2016Trial
- The Effect of Ecopipam on the Pharmacokinetics of Concomitant Medications.Clinical and translational science · 2026Article
- Variability in intestinal drug metabolizing enzymes and transporters in Crohn's disease and potential impact on oral drug absorption.British journal of clinical pharmacology · 2025Article
- Towards More Robust Evaluation of the Predictive Performance of Physiologically Based Pharmacokinetic Models: Using Confidence Intervals to Support Use of Model-Informed Dosing in Clinical Care.Clinical pharmacokinetics · 2024Article
- Distribution and elimination kinetics of midazolam and metabolites after post-resuscitation care: a prospective observational study.Scientific reports · 2024Observational
- Protocol of the IntenSify-Trial: An open-label phase I trial of the CYP3A inhibitor cobicistat and the cytostatics gemcitabine and nab-paclitaxel in patients with advanced stage or metastatic pancreatic ductal adenocarcinoma to evaluate the combination's pharmacokinetics, safety, and efficacy.Clinical and translational science · 2023Article
- CYP3A and CYP2C19 Activity Determined by Microdosed Probe Drugs Accurately Predict Voriconazole Clearance in Healthy Adults.Clinical pharmacokinetics · 2023Article
- Evaluation of CYP2C19 activity using microdosed oral omeprazole in humans.European journal of clinical pharmacology · 2022Article
- Sensitive UHPLC-MS/MS quantification method for 4β- and 4α-hydroxycholesterol in plasma for accurate CYP3A phenotyping.Journal of lipid research · 2022Article
- Short- and long-term effects of body weight loss following calorie restriction and gastric bypass on CYP3A-activity - a non-randomized three-armed controlled trial.Clinical and translational science · 2022Article
- The Oral Bioavailability and Metabolism of Midazolam in Stable Critically Ill Children: A Pharmacokinetic Microtracing Study.Clinical pharmacology and therapeutics · 2021Article
- Composite midazolam and 1'-OH midazolam population pharmacokinetic model for constitutive, inhibited and induced CYP3A activity.Journal of pharmacokinetics and pharmacodynamics · 2020Article
- Phase 0/microdosing approaches: time for mainstream application in drug development?Nature reviews. Drug discovery · 2020Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimWe aimed to establish a method to assess systemic and pre-systemic cytochrome P450 (CYP) 3A activity using ineffective microgram doses of midazolam.
methodsIn an open, one sequence, crossover study, 16 healthy participants received intravenous and oral midazolam at microgram (0.001 mg intravenous and 0.003 mg oral) and regular milligram (1 mg intravenous and 3 mg oral) doses to assess the linearity of plasma and urine pharmacokinetics.
resultsDose-normalized AUC and Cmax were 37.1 ng ml(-1 ) h [95% CI 35.5, 40.6] and 39.1 ng ml(-1) [95% CI 30.4, 50.2] for the microdose and 39.0 ng ml(-1 ) h [95% CI 36.1, 42.1] and 37.1 ng ml(-1) [95% CI 26.9, 51.3] for the milligram dose. CLmet was 253 ml min(-1) [95% CI 201, 318] vs. 278 ml min(-1) [95% CI 248, 311] for intravenous doses and 1880 ml min(-1) [95% CI 1590, 2230] vs. 2050 ml min(-1) [95% CI 1720, 2450] for oral doses. Oral bioavailability of a midazolam microdose was 23.4% [95% CI 20.0, 27.3] vs. 20.9% [95% CI 17.1, 25.5] after the regular dose. Hepatic and gut extraction ratios for microgram doses were 0.44 [95% CI 0.39, 0.49] and 0.53 [95% CI 0.45, 0.63] and compared well with those for milligram doses (0.43 [95% CI 0.37, 0.49] and 0.61 [95% CI 0.53, 0.70]).
conclusionThe pharmacokinetics of an intravenous midazolam microdose is linear to the applied regular doses and can be used to assess safely systemic CYP3A activity and, in combination with oral microdoses, pre-systemic CYP3A activity.
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