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Pharmacokinetics of n‐4‐hydroxyphenyl‐retinamide and the effect of its oral administration on plasma retinol concentrations in cancer patients
Author(s) -
Peng YeiMei,
Dalton William S.,
Alberts David S.,
Xu MinJian,
Lim Heidi,
Meyskens Frank L.
Publication year - 1989
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910430106
Subject(s) - pharmacokinetics , metabolite , oral administration , retinol , endocrinology , medicine , in vivo , chemistry , pharmacology , bioavailability , active metabolite , vitamin , biology , microbiology and biotechnology
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/m 2 ) in 3 cancer patients were the following: 4HPR, t β 1/2 = 13.7 hr, AUC = 3.49 μg.hr/ml, CL = 56.57 L/hr/m 2 ; 4MPR, t β 1/2 = 23.0 hr, AUC = 1.15 μg.hr/ml, CL = 239.29 L/hr/m 2 . 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.