HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Pharmacokinetics of N-4-hydroxyphenyl-retinamide and the effect of its oral administration on plasma retinol concentrations in cancer patients.

Abstract
Concurrent with a phase-II 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/day) [corrected] in 3 cancer patients were the following: 4HPR, t beta 1/2 = 13.7 hr, AUC = 3.49 micrograms.hr/ml, CL = 56.57 L/hr/m2; 4MPR, t beta 1/2 = 23.0 hr, AUC = 1.15 micrograms.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 ng/ml 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 37 degrees C in vitro did not reduce endogenous retinol levels, suggesting no direct chemical interaction between these 2 retinoids.
AuthorsY M Peng, W S Dalton, D S Alberts, M J Xu, H Lim, F L Meyskens Jr
JournalInternational journal of cancer (Int J Cancer) Vol. 43 Issue 1 Pg. 22-6 (Jan 15 1989) ISSN: 0020-7136 [Print] United States
PMID2521335 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Retinol-Binding Proteins
  • Retinol-Binding Proteins, Plasma
  • Vitamin A
  • Fenretinide
  • Tretinoin
  • N-(4-methoxyphenyl)retinamide
Topics
  • Administration, Oral
  • Breast Neoplasms (blood)
  • Chromatography, High Pressure Liquid
  • Drug Evaluation
  • Fenretinide
  • Humans
  • Melanoma (blood)
  • Mycosis Fungoides (blood)
  • Retinol-Binding Proteins (analysis)
  • Retinol-Binding Proteins, Plasma
  • Tretinoin (analogs & derivatives, metabolism, pharmacokinetics)
  • Vitamin A (blood)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: