Trial reportClinical pharmacology and therapeutics2020
The Effects of Weak and Strong CYP3A Induction by Rifampicin on the Pharmacokinetics of Five Progestins and Ethinylestradiol Compared to Midazolam.
Trial report in Clinical pharmacology and therapeutics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 29 citations in OpenAlex.
- Pharmacokinetics of dose-adjusted levonorgestrel emergency contraception combined with efavirenz-based antiretroviral therapy or rifampicin-containing tuberculosis regimens.Contraception · 2023Trial
- The effects of vilaprisan on the pharmacodynamics and pharmacokinetics of a combined oral contraceptive-A randomized controlled trial.British journal of clinical pharmacology · 2021Trial
- Application of Virtual Twin PBPK Models in Individuals with Obesity via CYP3A4 Phenotyping Using Endogenous Biomarker Data.Clinical pharmacology and therapeutics · 2026Article
- Assessment of the Drug-Drug Interaction Potential of Lotiglipron (PF-07081532) with Midazolam, Omeprazole, Dabigatran, Rosuvastatin, and the Oral Contraceptives Levonorgestrel and Ethinyl Estradiol.Journal of clinical pharmacology · 2026Article
- Effects of Ensitrelvir on the Pharmacokinetics of Combined Oral Contraceptives (Ethinyl Estradiol/Drospirenone) in Healthy Adult Women: A Phase 1 Fixed-Sequence, Multiple-Dose, Drug-Drug Interaction Study.Clinical drug investigation · 2026Article
- Pregnane X Receptor Regulates Human Endocrine System by Inducing Sex Hormone-Binding Globulin Expression.Basic & clinical pharmacology & toxicology · 2026Article
- A drug-drug interaction study to evaluate the effects of strong CYP3A4 inducer on the pharmacokinetics of segesterone acetate and ethinyl estradiol in a contraceptive vaginal system.Contraception and reproductive medicine · 2025Article
- Exploring Antibiotic-Mediated Disruption of Enterohepatic Circulation and Combined Oral Contraceptive Efficacy: A Systematic Review.Women's health reports (New Rochelle, N.Y.) · 2025Review
- Exploring the Feasibility of a Bracketing Approach Utilizing Modeling for Development of Long-Acting Injectables for Regulatory Approval-A Case Study Using Levonorgestrel.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Applications of the Cholesterol Metabolite, 4β-Hydroxycholesterol, as a Sensitive Endogenous Biomarker for Hepatic CYP3A Activity Evaluated within a PBPK Framework.Pharmaceutics · 2024Article
- Chemical manipulation of an activation/inhibition switch in the nuclear receptor PXR.Nature communications · 2024Article
- Physiologically-based pharmacokinetic modeling of prominent oral contraceptive agents and applications in drug-drug interactions.CPT: pharmacometrics & systems pharmacology · 2024Article
- Extracellular Vesicles as Surrogates for Drug Metabolism and Clearance: Promise vs. Reality.Life (Basel, Switzerland) · 2023Review
- Combined Oral Contraceptives As Victims of Drug Interactions.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- Science-Based Approach to Harmonize Contraception Recommendations in Clinical Trials and Pharmaceutical Labels.Clinical pharmacology and therapeutics · 2023Review
- Evaluation of the potential for pharmacokinetic interaction between tirabrutinib and levonorgestrel/ethinyl estradiol in healthy female volunteers.Clinical and translational science · 2022Article
- Male reproductive hormones in patients treated with pretomanid.The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease · 2022Article
- In vitro assessment of the potential for dolutegravir to affect hepatic clearance of levonorgestrel.HIV medicine · 2021Article
- Quantitative Assessment of Levonorgestrel Binding Partner Interplay and Drug-Drug Interactions Using Physiologically Based Pharmacokinetic Modeling.CPT: pharmacometrics & systems pharmacology · 2021Article
- Regulation of PXR in drug metabolism: chemical and structural perspectives.Expert opinion on drug metabolism & toxicologyReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It is known that co-administration of CYP3A inducers may decrease the effectiveness of oral contraceptives containing progestins as mono-preparations or combined with ethinylestradiol. In a randomized clinical drug-drug interaction study, we investigated the effects of CYP3A induction on the pharmacokinetics of commonly used progestins and ethinylestradiol. Rifampicin was used to induce CYP3A. The progestins chosen as victim drugs were levonorgestrel, norethindrone, desogestrel, and dienogest as mono-products, and drospirenone combined with ethinylestradiol. Postmenopausal women (n = 12-14 per treatment group) received, in fixed sequence, a single dose of the victim drug plus midazolam without rifampicin, with rifampicin 10 mg/day (weak induction), and with rifampicin 600 mg/day (strong induction). The effects on progestin exposure were compared with the effects on midazolam exposure (as a benchmark). Unbound concentrations were evaluated for drugs binding to sex hormone binding globulin. Weak CYP3A induction, as confirmed by a mean decrease in midazolam exposure by 46%, resulted in minor changes in progestin exposure (mean decreases: 15-37%). Strong CYP3A induction, in contrast, resulted in mean decreases by 57-90% (mean decrease in midazolam exposure: 86%). Namely, the magnitude of the observed induction effects varied from weak to strong. Our data might provide an impetus to revisit the currently applied clinical recommendations for oral contraceptives, especially for levonorgestrel and norethindrone-containing products, and they might give an indication as to which progestin could be used, if requested, by women taking weak CYP3A inducers-although it is acknowledged that the exact exposure-response relationship for contraceptive efficacy is currently unclear for most progestins.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.