A Pharmacokinetic Study of Intramuscular (IM) Parecoxib Sodium in Normal Subjects

• Published in: Journal of clinical pharmacology 2001-10, Vol.41 (10), p.1111-1119
• Main Authors: Karim, Aziz, Laurent, Aziz, Slater, Margaret E., Kuss, Michael E., Qian, Jiang, Crosby-Sessoms, Sharon L., Hubbard, Richard C.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Analysis of Variance; Anti-Inflammatory Agents, Non-Steroidal - adverse effects; Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics; Area Under Curve; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Cyclooxygenase Inhibitors - administration & dosage; Cyclooxygenase Inhibitors - adverse effects; Cyclooxygenase Inhibitors - pharmacokinetics; Double-Blind Method; Humans; Injections, Intramuscular; Isoxazoles - administration & dosage; Isoxazoles - adverse effects; Isoxazoles - pharmacokinetics; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Sulfonamides - adverse effects; Sulfonamides - pharmacokinetics
• ISSN: 0091-2700; 1552-4604
• DOI: 10.1177/00912700122012607

A single‐center, double‐blind, placebo‐controlled, randomized study was conducted to determine the pharmacokinetics, safety, and tolerability of single, rising intramuscular (IM) doses and the single maximum tolerated dose of parecoxib sodium, a prodrug of the novel COX‐2 selective anti‐inflammatory analgesic drug valdecoxib, in 56 healthy male volunteers, ages 18 to 45 years inclusive. Cohorts of up to 6 subjects in each dose schedule were administered either parecoxib sodium (1 mg, 2 mg, 5 mg, 10 mg, 20 mg, or 40 mg) or matching placebo. Following IM administration, serial blood samples for measurement of plasma concentrations of parecoxib, valdecoxib, and valdecoxib metabolite (M1) were collected at predetermined intervals (from 15 minutes prior to dose and through 96 hours postdose). Urine collections were obtained for drug assay (from −12 to 0 hours, 0 to 12 hours, and 12 to 24 hours postdose). After IM administration, peak plasma concentrations of parecoxib were reached within 15 minutes and then declined rapidly as prodrug was converted to the active moiety, valdecoxib. Change in plasma concentrations of valdecoxib, which declined more slowly (t1/2 = 5.4–9.9 hours), reflected transformation to several metabolites, one of which was the minor active metabolite M1. As measured by the AUC0–∞, Cmax, and XU0–24 of valdecoxib, parecoxib sodium demonstrated dose proportionality when administered in the range of 1 mg to 40 mg of parecoxib. All single IM doses up to the maximum of 40 mg of parecoxib, as well as concentrations of up to 20 mg/ml, were well tolerated.