Retinoids
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With the aromatic retinoic acid analog Tigason oral and intravenous pharmacokinetic studies have been performed in 5 normal volunteers. Simultaneous fitting of single i. v. and oral data to a three-compartment model assuming first-order absorption was possible. Using Nonlin parameter estimates of the single-dose data, one is able to predict the decline in plasma levels of parent drug following cessation of a 10 days multiple dosing regimen up to 24 hours. The model is however unable to predict a phase of prolonged elimination observed beyond 24 hours. Moreover in 5 patients, who underwent…mehr

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Produktbeschreibung
With the aromatic retinoic acid analog Tigason oral and intravenous pharmacokinetic studies have been performed in 5 normal volunteers. Simultaneous fitting of single i. v. and oral data to a three-compartment model assuming first-order absorption was possible. Using Nonlin parameter estimates of the single-dose data, one is able to predict the decline in plasma levels of parent drug following cessation of a 10 days multiple dosing regimen up to 24 hours. The model is however unable to predict a phase of prolonged elimination observed beyond 24 hours. Moreover in 5 patients, who underwent chronic therapy (8-15 months), substantial plasma levels of both unchanged drug and main metabolite (corre sponding carboxylic acid) were observed up to 140 days after cessation of the therapy. An apparent half-life of elimination of 80-100 days can be calculated. The drug appears to be stored at some yet unknown storage site. Investigation of metabolism of Tigason in rats and humans revealed 19different bio transformation products thus far, most of them appearing in the urine in low amounts (20010 of dose). A few of them (mainly the acid Ro 10-1670) after conjugation to glucuronic acid are excreted in the bile in high amounts (60-80% of dose). No drug appeared unchanged in the excreta after i. v. administration to rats. References 1. Bollag W (1971) Effects of vitamin A acid (NSC-122758) on transplantable and chemically-induced tumors. Cancer Chemother Rep 55:53-58 2.
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