Evaluation of new indomethacin dosage forms.
Indomethacin, an indole derivative nonsteroidal anti-inflammatory drug, has been available since the early 1960s in gelatin capsules. In 1982, a sustained release product, Indocin SR, was marketed. Awaiting marketing approval is a unique controlled release form of indomethacin, Indos. The disposition of indomethacin includes enterohepatic cycling and extensive metabolism to inactive metabolites. Enterohepatic cycling makes interpretation of bioavailability estimates of indomethacin dosage forms difficult. The relationship of indomethacin plasma concentration to therapeutic effects and side effects is inconclusive. It appears in vivo prostaglandin inhibition occurs at very low plasma concentrations that are achievable with all available dosage forms. Indocin SR is a sustained release capsule of indomethacin designed to deliver 25 mg of drug immediately and 50 mg gradually. Absolute bioavailability of the product is 80%. The plasma concentration-time curves do not show good sustained release characteristics; after four hours plasma concentrations resemble those seen with a single dose of regular capsule. The cost compared with Indocin is competitive. Indos is a zero-order release form of indomethacin. It is a unique drug delivery system that shows good controlled release characteristics. Bioavailability is 85%. Both Indocin SR and Indos are apparently therapeutically equivalent to indomethacin capsules. In elderly patients, Indos has been shown to be associated with fewer side effects than Indocin. Both Indocin SR and Indos have the advantage of once or twice daily dosing.
D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D001682:Biological Availability; D002214:Capsules; D003692:Delayed-Action Preparations; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage* / Q000378:metabolism; D007700:Kinetics; D009994:Osmolar Concentration; D010003:Osteoarthritis / Q000188:drug therapy
D002214:Capsules; D003692:Delayed-Action Preparations; D007213:Indomethacin