The effect of different doses of cyclosporin A on the systemic exposure of orally administered paclitaxel

Anti-cancer Drugs
Mirte M MalingréJ H M Schellens

Abstract

The objective of this study was to define the minimally effective dose of cyclosporin A (CsA) that would result in a maximal increase of the systemic exposure to oral paclitaxel. Six evaluable patients participated in this randomized cross-over study in which they received at two occasions two doses of 90 mg/m(2) oral paclitaxel 7 h apart in combination with 10 or 5 mg/kg CsA. Dose reduction of CsA from 10 to 5 mg/kg resulted in a statistically significant decrease in the area under the plasma concentration-time curve (AUC) and time above the threshold concentrations of 0.1 microM (T>0.1 microM) of oral paclitaxel. The mean (+/-SD) AUC and T>0.1 microM values of oral paclitaxel with CsA 10 mg/kg were 4.29+/-0.88 microM x h and 12.0+/-2.1 h, respectively. With CsA 5 mg/kg these values were 2.75+/-0.63 microM x h and 7.0+/-2.1 h, respectively (p=0.028 for both parameters). In conclusion, dose reduction of CsA from 10 to 5 mg/kg resulted in a significant decrease in the AUC and T>0.1 microM values of oral paclitaxel. Because CsA 10 mg/kg resulted in similar paclitaxel AUC and T>0.1 microM values compared to CsA 15 mg/kg (data which we have published previously), the minimally effective dose of CsA is determined at 10 mg/kg.

References

Dec 21, 1989·The New England Journal of Medicine·B D Kahan
Sep 13, 1984·The New England Journal of Medicine·B D MyersM Perlroth
Jun 7, 1980·British Medical Journal·D Dye, J Watkins
Jan 1, 1995·Cancer Investigation·M T HuizingJ H Beijnen
Jan 1, 1995·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·B C BaguleyP van Zijl
Feb 17, 1995·Journal of Chromatography. B, Biomedical Applications·M T HuizingJ H Beijnen
Jan 1, 1995·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·L GianniM J Egorin
Apr 13, 1995·The New England Journal of Medicine·E K Rowinsky, R C Donehower
Nov 1, 1993·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·M T HuizingJ H Beijnen
Dec 1, 1993·British Journal of Cancer·J E LiebmannJ B Mitchell
Jan 1, 1993·Cancer Chemotherapy and Pharmacology·N M LopesB K Bhuyan
Dec 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·M S ShetR W Estabrook
Jan 1, 1996·Anti-cancer Drugs·A SparreboomJ H Beijnen
Dec 15, 1995·Journal of Chromatography. B, Biomedical Applications·M T HuizingJ H Beijnen
Jan 1, 1997·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·M T HuizingJ H Beijnen
Mar 4, 1997·Proceedings of the National Academy of Sciences of the United States of America·A SparreboomO van Tellingen
Aug 5, 1998·Lancet·J M Meerum TerwogtJ H Schellens
Sep 25, 1999·British Journal of Cancer·O van TellingenJ H Beijnen
Jun 16, 2000·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·M M MalingréJ H Schellens

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Citations

Oct 17, 2003·Archives of Pharmacal Research·Hongjian ZhangSaeho Chong
May 9, 2006·Cancer Chemotherapy and Pharmacology·S A VeltkampJ H M Schellens
Jan 6, 2007·Cancer Chemotherapy and Pharmacology·S A VeltkampJ H M Schellens
Dec 6, 2011·Archives of Pharmacal Research·Ying ChenHong Liu
Apr 15, 2010·Investigational New Drugs·Roos L OostendorpO van Tellingen
May 20, 2008·Toxicology and Applied Pharmacology·B Frazier TaylorJ Christopher States
Mar 8, 2008·Journal of Controlled Release : Official Journal of the Controlled Release Society·Lev Bromberg
Mar 9, 2005·British Journal of Clinical Pharmacology·Milly E de JongeJos H Beijnen
Nov 20, 2009·Clinical Pharmacology and Therapeutics·S L W KoolenJ H M Schellens
Dec 17, 2011·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Joon Hee ParkHwa Jeong Lee
Nov 28, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·C M F KruijtzerP Baas
Jul 7, 2014·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Pingsheng HuangAnjie Dong

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