A clinical pharmacokinetic microdosing study of docetaxel with Japanese patients with cancer.
Ken-ichi Fujita, Etsuko Yoshino, Kaori Kawara, Kazuya Maeda, Hiroyuki Kusuhara, Yuichi Sugiyama, Taro Yokoyama, Toshikado Kaneta, Hiroo Ishida, Yasutsuna Sasaki
Cancer chemotherapy and pharmacology October 2015 DOI: 10.1007/s00280-015-2844-2 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Pharmacokinetic study Peer reviewed |
|---|---|
| Sample size | 9 |
| Population | Japanese patients with cancer |
| Intervention | Docetaxel |
| Dose | microdose: 100 μg/patient; therapeutic dose: 60-75 mg m(-2) |
| Duration | Microdose on day 1, therapeutic dose on day 8 |
| Measures | liquid chromatography-tandem mass spectrometry, two-compartment pharmacokinetic model, area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf) |
| Topics | Microdosing |
| Keywords | Docetaxel Microdose study Pharmacokinetics Α1-acid glycoprotein |
| Key points | Docetaxel clearance was 1.8-fold higher at the therapeutic dose than at the microdose (P = 0.0041), indicating marginal nonlinearity, which the authors attribute to saturation of plasma protein binding. Because the difference was within twofold, they conclude that microdose pharmacokinetics allow practically acceptable prediction of therapeutic-dose docetaxel disposition. |
Abstract
Whether microdosing studies can be used to evaluate the human pharmacokinetics of new anticancer drugs remains unclear. The disposition of docetaxel in cancer patients is linear in terms of dose proportionality. We examined whether the pharmacokinetics of docetaxel in a clinically relevant therapeutic dose could be predicted from the pharmacokinetics of a microdose of docetaxel in Japanese patients with cancer. A microdose of docetaxel (100 μg/patient) was given by 5-min intravenous infusion on day 1, followed by a therapeutic dose of docetaxel (60-75 mg m(-2)), given by 1-h intravenous infusion on day 8. Plasma docetaxel was analyzed by liquid chromatography-tandem mass spectrometry. A two-compartment pharmacokinetic model was used to calculate the area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf). Nine patients received both a microdose and therapeutic dose of docetaxel. The AUC0-inf after microdosing was 3640 ± 1150 ng h L(-1), while that after therapeutic dosing adjusted to 100 mg/patient was 2230 ± 757 µg h L(-1). The ratio of docetaxel clearance in therapeutic dose to that in microdose was 1.8 (P = 0.0041). Plasma α1-acid glycoprotein concentrations negatively correlated with docetaxel clearance at therapeutic dose, whereas the trend was weak at microdose. Docetaxel clearance showed marginal nonlinearity between microdose and therapeutic dose, presumably because of saturation of plasma protein binding; however, the magnitude was within twofold, allowing practically acceptable extrapolation.
Comparable studies
Other experimental studies on microdosing, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Microdosing Clinical Study: Pharmacokinetic, Pharmacogenomic (SLCO2B1), and Interaction (Grapefruit Juice) Profiles of Celiprolol Following the Oral Microdose and Therapeutic Dose Healthy volunteers matched for SLCO2B1 genotype | 2011 | Pharmacokinetic study | n = 30 |
| 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 |
Citations in the library
Cited by 2
Cites 3
- Use of microdosing to predict pharmacokinetics at the therapeutic dose: Experience with 5 drugs Clinical Pharmacology & Therapeutics September 1, 2006
- Impact of microdosing clinical study — Why necessary and how useful? Advanced Drug Delivery Reviews October 14, 2010
- Nonlinear Pharmacokinetics of Oral Quinidine and Verapamil in Healthy Subjects: A Clinical Microdosing Study Clinical Pharmacology & Therapeutics June 29, 2011