imrecoxib and Renal-Insufficiency

Renal insufficiency may influence the pharmacokinetics of drugs. We have investigated the pharmacokinetic parameters of imrecoxib and its two main metabolites in individuals with osteoarthritis (OA) with normal renal function and renal insufficiency, respectively.. This was a prospective, parallel, open, matched-group study in which 24 subjects were enrolled (renal insufficiency group, n = 12; healthy control group, n = 12). Blood samples of subjects administered 100 mg imrecoxib were collected at different time points and analyzed. Plasma concentrations of imrecoxib and its two metabolites (M1 and M2) were determined by the liquid chromatography-tandem mass spectrometry method, and pharmacokinetic parameters (clearance [CL], apparent volume of distribution [V. The exposure of imrecoxib in OA patients with renal insufficiency showed a decline compared to that in healthy subjects. However, in patients with renal insufficiency the exposure of M2 was markedly increased and the CL was noticeably reduced. These results indicate that the dosage of imrecoxib should be reduced appropriately in patients with renal insufficiency.

Topics: Adult; Aged; Cyclooxygenase 2 Inhibitors; Drug Interactions; Female; Humans; Male; Middle Aged; Osteoarthritis; Pyrroles; Renal Insufficiency; Sulfides

Topics: Humans; Pyrroles; Renal Insufficiency; Sulfides

Topics: Humans; Pyrroles; Renal Insufficiency; Sulfides

Imrecoxib is a new moderately selective cyclooxygenase-2 (COX-2) inhibitor. A previous study has shown that drug exposure differs significantly in renally impaired patients. We aim to describe the population pharmacokinetics (PPK) of imrecoxib (M0) and its two metabolites (M1, M2) to provide a theoretical basis for investigating imrecoxib doses for renally impaired patients.. Using PPK analysis, 24 patients with 257 different plasma concentrations were studied. Of these, 12 had severe renal impairment and 12 had normal renal function. The dose regimen was simulated based on the final model to compare the ratio (Cu,ss/IC50) of the average unbound concentration at steady state (Cu,ss) to the half-maximal inhibitory concentration (IC50) of COX-2.. Imrecoxib and its metabolite concentrations were satisfactorily described by a two-compartment with first-order transit absorption model for imrecoxib and a one-compartment model for its metabolites. Renal function was a significant binary covariate. Scenarios of '75 mg q12h' and '50 mg q8h' in renally impaired patients had similar Cu,ss/IC50 values with a '100 mg q12h' regimen in subjects with normal renal function.. A PPK model of imrecoxib and its two metabolites is presented. The renal insufficiency regimen should be reduced to '75 mg q12h' or '50 mg q8h'.

Topics: Cyclooxygenase 2 Inhibitors; Humans; Pyrroles; Renal Insufficiency; Sulfides