Home
Resources
Publications
Effects of Prednisone on Docetaxel Pharmacokinetics in Men With Metastatic Prostate Cancer: A Randomized Drug-Drug Interaction Study

Effects of Prednisone on Docetaxel Pharmacokinetics in Men With Metastatic Prostate Cancer: A Randomized Drug-Drug Interaction Study

Bodine P S Belderbos, Koen G A M Hussaarts, Leonie J van Harten, Esther Oomen-de Hoop, Peter de Bruijn, Paul Hamberg, Robbert J van Alphen, Brigitte C M Haberkorn, Martijn P Lolkema, Ronald de Wit, Robert J van Soest, etc.

Br J Clin Pharmacol. 2019 May;85(5):986-992.

PMID: 30737835

Abstract:

Aims:
Docetaxel has been approved for the treatment of metastatic prostate cancer in combination with prednisone. Since prednisone is known to induce the cytochrome P450 iso-enzyme CYP3A4, which is the main metabolizing enzyme of docetaxel in the liver, a potential drug-drug interaction may occur. In this prospective randomized pharmacokinetic cross-over study we investigated docetaxel exposure with concomitant prednisone, compared to docetaxel monotherapy in men with metastatic prostate cancer.
Methods:
Patients scheduled to receive at least 6 cycles of docetaxel (75 mg/m2 ) and who gave written informed consent were randomized to receive either the 1st 3 cycles, or the last 3 consecutive cycles with prednisone (twice daily 5 mg). Pharmacokinetic blood sampling was performed during cycle 3 and cycle 6. Primary endpoint was difference in docetaxel exposure, calculated as area under the curve (AUC0-inf ) and analysed by means of a linear mixed model. Given the cross-over design the study was powered on 18 patients to answer the primary, pharmacokinetic, endpoint.
Results:
Eighteen evaluable patients were included in the trial. Docetaxel concentration with concomitant prednisone (AUC0-inf 2784 ng*h/mL, 95% confidence interval 2436-3183 ng*h/mL) was similar to the concentration of docetaxel monotherapy (AUC0-inf 2647 ng*h/mL, 95% confidence interval 2377-2949 ng*h/mL). Exploratory analysis showed no toxicity differences between docetaxel monotherapy and docetaxel cycles with prednisone.
Conclusion:
No significant difference in docetaxel concentrations was observed. In addition, we found similar toxicity profiles in absence and presence of prednisone. Therefore, from a pharmacokinetic point of view, docetaxel may be administrated with or without prednisone.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP114977285	Docetaxel		114977-28-5	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: