A Food-Effect Study to Evaluate the Oral Bioavailability of Desidustat.

Abstract

This randomized, single-treatment, 2-sequence study evaluated the food effect on oral bioavailability of desidustat. Healthy adult male and female subjects were enrolled and randomly assigned to receive desidustat 50mg orally in a fasting state in one period and a fed state in the other period. A standardized high-fat, high-calorie breakfast was served to assess the food effect. The pharmacokinetic results showed that the time to maximum blood concentration of desidustat was delayed significantly (P<.0001) in the fed state compared to the fasting state. The ingestion of food decreased the maximum blood concentration (Cmax ) compared to the fasting state (mean Cmax , 3248ng/mL in the fed state vs 5496ng/mL in the fasting state). The geometric mean ratio of fed/fasting for log-normal (ln) Cmax was 57. The exposure decreased in the fed state compared to the fasting state (mean area under the concentration-time curve [AUC] over the dosing interval, 25 559ng•h/mL in the fed state versus 33 705ng•h/mL in the fasting state; mean AUC from time 0 to infinity [AUC0-∞ ], 25,910ng•h/mL in the fed state vs 34 233ng•h/mL in the fasting state). The geometric mean ratio of fed/fasting for lnAUC from time 0 to the last quantifiable concentration and ln AUC0- ∞ was 77 and 76, respectively. The 90%CI of fed/fasting ratio of the geometric mean of lnCmax , AUC over the dosing interval, and AUC0-∞ of desidustat 50mg did not fall within 80%-125% margin. Therefore, the absence of food effect could not be established. It can be inferred that food has a significant effect on the oral absorption of desidustat. Therefore, food must not be consumed 1hour before and 2hours after the oral administration of desidustat.