ArticleClinical pharmacokinetics2020
Oral Yohimbine as a New Probe Drug to Predict CYP2D6 Activity: Results of a Fixed-Sequence Phase I Trial.
Article in Clinical pharmacokinetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 16 citations in OpenAlex.
- Sex-Dependent Effects of CYP2D6 on the Pharmacokinetics of Berberine in Humans.Clinical pharmacology and therapeutics · 2025Trial
- Time Course of the Interaction Between Oral Short-Term Ritonavir Therapy with Three Factor Xa Inhibitors and the Activity of CYP2D6, CYP2C19, and CYP3A4 in Healthy Volunteers.Clinical pharmacokinetics · 2024Trial
- Evaluation of Hydroxychloroquine as a Perpetrator on Cytochrome P450 (CYP) 3A and CYP2D6 Activity with Microdosed Probe Drugs in Healthy Volunteers.European journal of drug metabolism and pharmacokinetics · 2024Trial
- Article
- ChatGPT does make up scientific references: should it be currently renamed CheatGPT?European journal of clinical pharmacology · 2024Article
- Multifaced Nature of Yohimbine-A Promising Therapeutic Potential or a Risk?International journal of molecular sciences · 2024Review
- The Use of Microdosing for In vivo Phenotyping of Cytochrome P450 Enzymes: Where Do We Stand? A Narrative Review.European journal of drug metabolism and pharmacokinetics · 2024Review
- Pharmacokinetics of a microdosed cocktail of three direct oral anticoagulants in children with congenital heart defects: study protocol for a single-centre clinical trial (DOAC-Child).BMJ paediatrics open · 2023Article
- A literature perspective on the pharmacological applications of yohimbine.Annals of medicine · 2022Review
- An Investigation of O-Demethyl Tramadol/Tramadol Ratio for Cytochrome P450 2D6 Phenotyping: The CYTRAM Study.Pharmaceutics · 2022Article
- Evaluation of CYP2C19 activity using microdosed oral omeprazole in humans.European journal of clinical pharmacology · 2022Article
- CYP2D6 phenotype explains reported yohimbine concentrations in four severe acute intoxications.Archives of toxicology · 2021Article
- Article
- Pharmacogenetic analyses in people with dementia in Northeast Germany.Alzheimer's & dementia (Amsterdam, Netherlands)Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveYohimbine pharmacokinetics were determined after oral administration of a single oral dose of yohimbine 5 mg and a microdose of yohimbine 50 µg in relation to different cytochrome P450 (CYP) 2D6 genotypes. The CYP2D6 inhibitor paroxetine was used to investigate the influence on yohimbine pharmacokinetics. Microdosed midazolam was applied to evaluate a possible impact of yohimbine on CYP3A activity and the possibility of combining microdosed yohimbine and midazolam to simultaneously determine CYP2D6 and CYP3A activity.
methodsIn a fixed-sequence clinical trial, 16 healthy volunteers with a known CYP2D6 genotype [extensive (10), intermediate (2) and poor (4) metaboliser] received an oral dose of yohimbine 50 µg, yohimbine 5 mg at baseline and during paroxetine as a CYP2D6 inhibitor. Midazolam (30 µg) was co-administered to determine CYP3A activity at each occasion. Plasma concentrations of yohimbine, its main metabolite 11-OH-yohimbine, midazolam and paroxetine were quantified using validated liquid chromatography-tandem mass spectrometry assays.
resultsPharmacokinetics of yohimbine were highly variable and a CYP2D6 genotype dependent clearance was observed. After yohimbine 5 mg, the clearance ranged from 25.3 to 15,864 mL/min and after yohimbine 50 µg, the clearance ranged from 39.6 to 38,822 mL/min. A more than fivefold reduction in clearance was caused by paroxetine in CYP2D6 extensive metabolisers, while the clearance in poor metabolisers was not affected. Yohimbine did not alter CYP3A activity as measured by microdosed midazolam.
conclusionsThe pharmacokinetics of yohimbine were highly correlated with CYP2D6, which was further supported by the clearance inhibition caused by the CYP2D6 inhibitor paroxetine. With these data, yohimbine is proposed to be a suitable probe drug to predict CYP2D6 activity. In addition, the microdose can be used in combination with microdosed midazolam to simultaneously evaluate CYP2D6 and CYP3A activity without any interaction between the probe drugs and because the microdoses exert no pharmacological effects. CLINICAL
trial registrationEudraCT2017-001801-34.
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