The effect of food on the absorption of 14C-SDZ FOX 988, an antidiabetic agent, in healthy human volunteers.
The objective of this study is to examine the effect of food on oral absorption of SDZ FOX 988 (FOX 988), an antidiabetic agent, and circulating levels of its active metabolite, SDZ 53-450 (53-450). Sixteen normal volunteers received a single 10 mg dose of 14C-FOX 988, either as gelatin capsules or in a suspension (0.5% CMC). For subjects receiving each formulation, four subjects received a meal, consisting of 50% fat by calories, immediately following dosing, while the other four received the same meal at 2 h post-dose. Serial blood, urine, and fecal samples were collected for 120 h and analyzed for total radioactivity. Blood concentrations of 53-450 were analyzed using an HPLC-UV method. Concomitant administration with food increased the extent of FOX 988 absorption from either suspension or capsule, as shown by an increase in AUC and in urinary recovery of radioactivity. Blood concentrations of 53-450 were only detected in subjects receiving food at dosing. No difference in absorption was observed between the capsule and the suspension. Results from this study showed that oral absorption of FOX 988 is enhanced by co-administration of food in normal volunteers.