Dissolution rate-limited absorption and complete bioavailability of roquinimex in man

In order to investigate the bioavailability and the rate-limiting-step of t he absorption of roquinimex, an oral solution and a tablet formulation (Lin omide(R)) were given to healthy volunteers. The study was conducted as a ra ndomized three-period crossover study in seven male and seven female health y volunteers. The subjects received an intravenous infusion, an oral soluti on and an oral tablet formulation each of 5 mg (about 0.07 mg kg(-1)), as s ingle doses after an overnight fast on three occasions, with a wash-out per iod of 3 weeks in between. Venous blood samples were taken over 7 days and the plasma concentrations of roquinimex were determined by high-performance liquid chromatography (HPLC) with ultraviolet (UV)-detection. The pharmaco kinetics of roquinimex was characterized by a low plasma clearance, 4.9 mt h(-1) kg(-1) and a small volume of distribution, 0.22 L kg(-1). The oral bi oavailability of the drug was complete for both the solution and the tablet formulation. The absorption rate was faster for the solution than for the tablet. The disposition of roquinimex was biphasic, with a terminal disposi tion half-life of 32 h. Between 4 and 8 hours after dosing, a secondary pla sma peak was observed, indicating enterohepatic circulation of the drug. No major sex differences were shown in the pharmacokinetics of roquinimex. In conclusion, dissolution rate-limited absorption of roquinimex was shown, w hich demonstrates that disintegration and dissolution of the tablet play a major role in the absorption process of roquinimex. Despite the delayed abs orption after administration of the tablet, the extent of absorption was co mplete. Copyright (C) 1999 John Wiley & Sons, Ltd.