Pharmacokinetics of n-4-hydroxyphenyl-retinamide and the effect of its oral administration on plasma retinol concentrations in cancer patients
✍ Scribed by Yei-Mei Peng; William S. Dalton; David S. Alberts; Min-Jian Xu; Heidi Lim; Frank L. Meyskens JR.
- Publisher
- John Wiley and Sons
- Year
- 1989
- Tongue
- French
- Weight
- 449 KB
- Volume
- 43
- Category
- Article
- ISSN
- 0020-7136
No coin nor oath required. For personal study only.
✦ Synopsis
Concurrent with a phase4 trial of 4HPR in patients with various cancers, we studied the plasma pharmacokinetics of both 4HPR and its major metabolite 4MPR as well as the effect of 4HPR administration on plasma retinol concentrations using a simple, specific and sensitive HPLC procedure. Initial estimates of plasma pharmacokinetic parameters after oral administration of 4HPR (300 mg/m2) in 3 cancer patients were the following: 4HPR, = 13.7 hr, A U C = 3.49 pg.hr/ mi, CL = 56.57 L/hr/m2; 4MPR, t''% = 23.0 hr, A U C = 1.15 Fg.hr/ml, CL = 239.29 L/hr/m2. We also found that oral administration of 4HPR resulted in a rapid, profound and significant reduction in plasma retinol concentrations. The mean plasma retinol concentrations for 9 patients decreased 60% from baseline to below 200 nglml within 1-2 weeks of 4HPR dosing initiation. In addition, there was a concurrent, significant reduction in plasma retinol-binding protein levels in these patients. The mechanism whereby 4HPR reduces plasma retinol levels in vivo has not been determined. The addition of 4HPR to pooled human plasma at 37OC in vitro did not reduce endogenous retinol levels, suggesting no direct chemical interaction between these 2 retinoids.