关键词： Pharmacokinetic Rofecoxib
Pharmacokinetic Evaluation of Rofecoxib
Comparison of Tablet and Suspension Formulations
Posted 09/16/2003
Jules I. Schwartz, Patrick J. Larson, Arturo G. Porras, Kala-Jyoti Viswanathan-Aiyer, Nancy G.B. Agrawal, Kenneth C. Lasseter, Ralph S. Mazenko, Sheila A. Merschman, Barry J. Gertz
Abstract and Introduction
Abstract
Objective: Rofecoxib suspension is a formulation developed to increase the convenience of rofecoxib therapy for patients who have difficulty swallowing tablets. This open-label, two-part study compared the single-dose pharmacokinetics of rofecoxib tablets and rofecoxib suspension in healthy subjects.
Design and study participants: Part I was a two-period crossover study that assessed the bioequivalence of the 12.5mg/5mL rofecoxib suspension and the 12.5mg rofecoxib tablet in 24 healthy subjects (12 men and 12 women). Part II was a crossover study in 24 additional healthy subjects (12 men and 12 women) that determined the bioequivalence of the rofecoxib 25mg/5mL suspension and the 25mg rofecoxib tablet.
Results: No clinically meaningful differences between rofecoxib tablet and suspension were apparent with respect to the rofecoxib area under the concentration-time curve from time zero to infinity (AUC0-) and maximum plasma concentration (Cmax), the primary measures of bioequivalence. At the 12.5mg and 25mg doses, the 90% CI for the geometric mean ratio (suspension/tablet) of both AUC0- and Cmax fell within the prespecified interval for bioequivalence (0.80-1.25).
Conclusions: The rofecoxib suspension is bioequivalent to the rofecoxib tablet at single oral doses of 12.5mg and 25mg in healthy volunteers. The convenience and ease of administration of rofecoxib suspension may translate into increased compliance with therapy compared with a conventional solid tablet formulation, particularly for elderly patients.
Introduction
Rofecoxib is a selective cyclo-oxygenase (COX)-2 inhibitor that has demonstrated anti-inflammatory and analgesic efficacy comparable to that of many nonspecific COX-1/COX-2 inhibitors but has demonstrated an improved gastrointestinal safety profile.[1-4] Numerous studies demonstrate the efficacy of rofecoxib in treating osteoarthritis and rheumatoid arthritis as well as pain associated with dental and orthopaedic surgery and primary dys-menorrhoea.[5-12]
For some patients, especially elderly patients, compliance with once-daily rofecoxib therapy may be influenced by the ease with which they can swallow tablets. To improve the convenience of rofecoxib therapy, a suspension formulation of rofecoxib was developed to benefit patients who have difficulty swallowing as well as those who prefer an alternative to tablets. In addition, the rofecoxib suspension will avoid the possibility of rofecoxib tablets becoming stuck in the oesophagus. Tablets lodging in the oesophagus is a general phenomenon relating to tablet formulations and has been reported to occur in at least 20% of subjects participating in clinical studies where small volumes of water were used to take medications in tablet form.[13-16]
This open-label study was designed to evaluate the bioequivalence of rofecoxib tablets (12.5mg and 25mg) and a rofecoxib suspension formulation at the same corresponding strengths (12.5mg/5mL and 25mg/5mL).
