PLASMA KINETICS OF ORAL RETINOL IN CANCER-PATIENTS

  • 1 January 1984
    • journal article
    • research article
    • Vol. 68  (9) , 1125-1133
Abstract
Concurrent with a phase I traial of retinol in patients with advanced cancer, the plasma kinetics of both retinol and its major metabolites, retinyl palmitate and retinyl stearate were studied. Retinol was administered to 12 patients in daily oral doses of 60,000, 100,000, 150,000 or 200,000 U/m2. Patients remained on treatment until the development of dose-limiting toxic effects or disease progression. Retinoid plasma kinetics were studied on the 1st day of treatment, at wk 2 and 4, and every 2-3 mo. thereafter as long as the patient remained on therapy. A high-performance liquid chromatography assay was used to quantitate the plasma concentration of both retinol and its fatty acid esters. There was no significant change in the plasma retinol concentration up to 24 h after a single oral dose of retinol (P < 0.05). However, the plasma concentration of retinyl palmitate and retinyl stearate markedly increased with a mean time to peak plasma concentration fo 4.3 .THETA. 0.7h. REtinyl palmitate rapidly disappeared from the plasma with an initial phase half-life of 2.2 .+-. 0.9 h. The terminal phase half-life appeared prolonged and could not be accurately determined. Retinyl stearate was detected in the plasma of all patients with plasma concentrations paralleling and ranging from 20 to 40% those of retinyl palmitate. With prolonged retinol administration, peak plasma retinyl palmitate concentrations increased with both increasing retinol dose (P < 0.001) and increasing duration of treatment (P = 0.001). In 3 patients with low pretreatment plasma retinol concentrations, daily retinol administration was associated with a rise in plasma retinol concentration. Because only 1 patient developed serious toxic effects and all patients had markedly increased plasma concentrations of retinyl esters, no conclusion could be made about the relationship between plasma retinyl ester concentration and retinol toxicity.