Pharmacokinetic profile of parecoxib sodium, an injectable prodrug of the Cox-2-selective inhibitor, valdecoxib

Background Parecoxib sodium is an injectable prodrug of the Cox-2 inhibitor, valdecoxib in regulatory review in the US for the management of acute pain. Aim To compare the pharmacokinetic (PK) profiles of valdecoxib after administration of IV and IM parecoxib sodium relative to valdecoxib (BEXTRA®) tablets. Methods PK data were obtained from a study comparing single and multiple 5, 10, and 20 mg doses of oral valdecoxib tablet and IV parecoxib sodium solution (n=36), and a study comparing 20 mg IM and IV parecoxib sodium solution (n=16) in healthy volunteers. Results The 90% CIs for oral/IV treatment ratios of valdecoxib AUC after adjusting for molecular weight difference between parecoxib and valdecoxib were within 84–118% across single and multiple doses of 5, 10 and 20 mg. IM and IV parecoxib sodium were bioequivalent for valdecoxib AUC and Cmax. Valdecoxib Cmax was observed around 0.5, 0.8 and 2.3 hours after IV and IM parecoxib sodium and oral valdecoxib tablets, respectively, with mean oral/IV ratios within 0.51–0.78 due to the rapid conversion of parecoxib sodium (t1/2~22 min) to valdecoxib. Valdecoxib T1/2 (~8 hours) was unaffected by route of administration. Conclusions The pharmacokinetic profile of valdecoxib is similar when administered orally as valdecoxib tablets or as IM/IV parecoxib sodium, indicating no PK limitations to transitioning from parenteral to oral treatment. Clinical Pharmacology & Therapeutics (2005) 77, P48–P48; doi: 10.1016/j.clpt.2004.12.077