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

Y. M. Peng, W. S. Dalton, David S Alberts, M. J. Xu, H. Lim, F. L. Meyskens

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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/m2) in 3 cancer patients were the following: 4HPR, t( 1/2 )(β) = 13.7 hr, AUC = 3.49 μg.hr/ml, CL = 56.57 L/hr/m2; 4MPR, t( 1/2 )(β) = 23.0 hr, AUC = 1.15 μg.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°C in vitro did not reduce endogenous retinol levels, suggesting no direct chemical interaction between these 2 retinoids.

Original languageEnglish (US)
Pages (from-to)22-26
Number of pages5
JournalInternational Journal of Cancer
Volume43
Issue number1
StatePublished - 1989

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Fenretinide
Vitamin A
Oral Administration
Pharmacokinetics
Neoplasms
Area Under Curve
Plasma Retinol-Binding Proteins
Retinoids
High Pressure Liquid Chromatography

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Pharmacokinetics of N-4-hydroxyphenyl-retinamide and the effect of its oral administration on plasma retinol concentrations in cancer patients. / Peng, Y. M.; Dalton, W. S.; Alberts, David S; Xu, M. J.; Lim, H.; Meyskens, F. L.

In: International Journal of Cancer, Vol. 43, No. 1, 1989, p. 22-26.

Research output: Contribution to journalArticle

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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/m2) in 3 cancer patients were the following: 4HPR, t( 1/2 )(β) = 13.7 hr, AUC = 3.49 μg.hr/ml, CL = 56.57 L/hr/m2; 4MPR, t( 1/2 )(β) = 23.0 hr, AUC = 1.15 μg.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°C in vitro did not reduce endogenous retinol levels, suggesting no direct chemical interaction between these 2 retinoids.",
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AU - Lim, H.

AU - Meyskens, F. L.

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