Pharmacokinetics of chronically administered all-trans-retinoyl-β-glucuronide in mice

Add time:08/22/2019    Source:sciencedirect.com

After the subcutaneous injection of retinoyl β-glucuronide (RAG), both RAG and retinoic acid (RA), formed by the hydrolysis of RAG in vivo, achieved peak plasma concentrations within 1–2 h. Thereafter, RA was rapidly cleared from the plasma whereas RAG was eliminated much more slowly. No significant changes were noted in the peak (2 h) plasma levels of RAG for treatment periods up to 56 days (one injection of RAG/day), in the clearance rate of RAG from plasma, or in plasma retinol concentrations. Similarly, no consistent decrease in plasma levels of the RA hydrolysis product was observed. Mice undergoing these long-term chronic treatments with RAG did not show any clinical manifestations of retinoid toxicity. Taken together, our findings that chronic dosing with RAG produces sustained levels of both the parent compound and the RA hydrolysis product, combined with the apparent low toxicity of RAG, suggest that RAG could be a safe and useful alternative to some retinoids which are presently being utilized in the clinic.

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