Risedronate gastrointestinal absorption is independent of site and rate of administration

• Published in: Pharmaceutical research Vol. 15; no. 2; pp. 228 - 232
• Main Authors: MITCHELL, D. Y, EUSEBIO, R. A, DUNLAP, L. E, PALLONE, K. A, NESBITT, J. D, RUSSELL, D. A, CLAY, M. E, BEKKER, P. J
• Format: Journal Article
• Language: English
• Published: New York, NY Springer 01-02-1998; Springer Nature B.V
• Subjects: Area Under Curve; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Calcium Channel Blockers - administration & dosage; Calcium Channel Blockers - adverse effects; Calcium Channel Blockers - blood; Calcium Channel Blockers - pharmacokinetics; Dosage Forms; Duodenum - metabolism; Etidronic Acid - administration & dosage; Etidronic Acid - adverse effects; Etidronic Acid - analogs & derivatives; Etidronic Acid - blood; Etidronic Acid - pharmacokinetics; Gastric Mucosa - metabolism; Humans; Ileum - metabolism; Intestinal Absorption; Male; Medical sciences; Pharmacology. Drug treatments; Risedronic Acid; Human; Urine; Stomach; Duodenum; Digestive system; Single dose; Oral administration; Diphosphonic acid derivatives; Gastrointestinal; Route of administration; Bisphosphonates; Blood; Intragastric administration; Randomization; Absorption; Risedronic acid; Clinical trial; Serum; Intraduodenal administration; Pharmacokinetics
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1023/A:1011910517200

Two studies were conducted to compare the absorption of risedronate administered as a solution to three different gastrointestinal sites (study A) and to determine the extent of absorption of risedronate solution administered by rapid and slow infusion to the second part of the duodenum (study B).
Each study was designed as a single-dose, crossover (three periods, study A; two periods, study B) trial in healthy male subjects, with a 14-day washout period between dosing. Subjects fasted overnight before drug administration and for 4 hours after drug administration. In study A, a risedronate solution of 40 mg in 30 mL of water was administered directly into the stomach, the second 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 risedronate solution of 40 mg in 30 mL of water was administered directly into the second part of the duodenum over 1 minute and over 1 hour in a randomized, two-period crossover design. Serum and urine samples were obtained for 48 hours after dosing for risedronate analysis.
Eight subjects completed each study. No statistically significant site-specific differences in any pharmacokinetic parameter were observed (study A). Based on the area under the serum concentration-time profile and the amount of drug excreted in the urine unchanged, the extent of risedronate absorption did not differ significantly following a rapid or a slow infusion (study B). Only minor symptomatic complaints were reported by subjects, such as headaches and body aches.
These studies indicate that the rate and extent of risedronate absorption are independent of the site of administration along the gastrointestinal tract, and that the extent of absorption is not affected by the rate of administration.