Microdosing Clinical Study: Pharmacokinetic, Pharmacogenomic (SLCO2B1), and Interaction (Grapefruit Juice) Profiles of Celiprolol Following the Oral Microdose and Therapeutic Dose
Ichiro Ieiri, Yohei Doi, Kazuya Maeda, Tomohiro Sasaki, Miyuki Kimura, Takeshi Hirota, Takeshi Chiyoda, Mayuko Miyagawa, Shin Irie, Kazuhide Iwasaki, Yuichi Sugiyama
The Journal of Clinical Pharmacology May 19, 2011 DOI: 10.1177/0091270011408612 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Pharmacokinetic study Peer reviewed |
|---|---|
| Sample size | 30 |
| Population | Healthy volunteers matched for SLCO2B1 genotype |
| Interventions | Celiprolol Fexofenadine Atenolol Grapefruit juice |
| Dose | microdose (totally 97.5 µg) and therapeutic dose (100 mg) of celiprolol |
| Measures | AUC(0-24) |
| Topics | Microdosing |
| Keywords | Microdose Pharmacokinetics Celiprolol Grapefruit juice Pharmacogenomics Pharmacology Pharmacokinetic interaction Plasma concentration Oral administration Therapeutic index Drug interaction |
| Citations | 106 |
| Key points | The SLCO2B1 polymorphism affects celiprolol exposure only at a therapeutic dose, likely due to saturation of efflux transport systems at that dose. |
Abstract
The authors evaluated the contribution of the SLCO2B1 polymorphism to the pharmacokinetics of celiprolol at a microdose (MD) and therapeutic dose (TD) and compared pharmacokinetic proportionality between the 2 dose forms in 30 SLCO2B1 genotype-matched healthy volunteers. Three drugs (celiprolol, fexofenadine, and atenolol) were orally administered as a cassette dosing following the MD (totally 97.5 µg) and then a TD (100 mg) of celiprolol, with and without grapefruit juice. The mean AUC(0-24) of celiprolol was lower in SLCO2B1*3/*3 individuals (775 ng·h/mL) than in *1/*3 (1097 ng·h/mL) and *1/*1 (1547 ng·h/mL) individuals following the TD, and this was confirmed in population pharmacokinetic analysis with statistical significances; however, SLCO2B1 genotype-dependent differences disappeared following the MD. Dose-normalized AUC of celiprolol at the MD was much lower than that at the TD, explained by the saturation of the efflux transporter. Thus, the effect of SLCO2B1 polymorphism on the AUC of celiprolol clearly observed only at the TD may be due to the saturation of the efflux transport systems.
Comparable studies
Other experimental studies on microdosing, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Microdosing psychedelics has no impact on cognitive function in naturalistic settings Participants during their microdosing regimen | 2023 | Observational within-subjects design | n = 17 |
| PK and PK / PD Modeling of Bcl2 Inhibitor S65487 in Patients With AML and Investigation of Nonlinearity With Microdosing Phase I/II cancer patients and healthy volunteers | 2026 | Pharmacokinetic/pharmacodynamic modeling study | |
| Technical pen-based printhead for high-precision microdosing of personalized therapies. | 2026 | Experimental study | |
| Analysis of Serotonin in Caenorhabditis Elegans Subjected to Micro-Dosing with Psilocybin| Iris Publishers Caenorhabditis elegans | 2025 | Experimental study | |
| Microdosing ketamine in Drosophila does not inhibit SERT like SSRIs, but causes behavioral changes mediated by glutamate and serotonin receptors Drosophila melanogaster larvae | 2023 | Experimental study |
Citations in the library
Cited by 6
- Phase 0/microdosing approaches: time for mainstream application in drug development? Nature Reviews Drug Discovery September 8, 2020
- Microdosing and drug development: past, present and future Expert Opinion on Drug Metabolism & Toxicology April 4, 2013
- Microdosing and Other Phase 0 Clinical Trials: Facilitating Translation in Drug Development Clinical and Translational Science February 26, 2016
- Microdosing: A Critical Assessment of Human Data Journal of Pharmaceutical Sciences August 23, 2012
- Predicting Drug Candidate Victims of Drug-Drug Interactions, using Microdosing Clinical Pharmacokinetics February 16, 2012
and 1 more in the library
Cites 3
- Positron emission tomography microdosing: a new concept with application in tracer and early clinical drug development European Journal of Clinical Pharmacology September 1, 2003
- Big physics, small doses: the use of AMS and PET in human microdosing of development drugs Nature Reviews Drug Discovery February 28, 2003
- Use of microdosing to predict pharmacokinetics at the therapeutic dose: Experience with 5 drugs Clinical Pharmacology & Therapeutics September 1, 2006