RISEDRONATE GASTROINTESTINAL ABSORPTION IS INDEPENDENT OF SITE AND RATE OF ADMINISTRATION

Purpose. Two studies were conducted to compare the absorption of rised ronate administered as a solution to three different gastrointestinal sites (study A) and to determine the extent of absorption of risedrona te solution administered by rapid and slow infusion to the second part of the duodenum (study B). Methods. Each study was designed as a sing le-dose, crossover (three periods, study A; two periods, study B) tria l in healthy male subjects, with a 14-day washout period between dosin g. Subjects fasted overnight before drug administration and for 4 hour s after drug administration. In study A, a risedronate solution of 40 mg in 30 mt of water was administered directly into the stomach, the s econd part of the duodenum, or the terminal ileum over 1 minute via a nasoenteral tube in a three-period crossover design. In study B, a ris edronate solution of 40 mg in 30 mt of water was administered directly into the second part of the duodenum over 1 minute and over I hour in a randomized, two-period crossover design. Serum and urine samples we re obtained for 48 hours after dosing for risedronate analysis. Result s, Eight subjects completed each study. No statistically significant s ite-specific differences in any pharmacokinetic parameter were observe d (study A). Based on the area under the serum concentration-time prof ile and the amount of drug excreted in the urine unchanged, the extent of risedronate absorption did not differ significantly following a ra pid or a slow infusion (study B). Only minor symptomatic complaints we re reported by subjects, such as headaches and body aches. Conclusions , These studies indicate that the rate and extent of risedronate absor ption are independent of the site of administration along the gastroin testinal tract, and that the extent of absorption is not affected by t he rate of administration.