Comparative Bioavailability and Tolerability of Single and Multiple Doses of 2 Diclofenac Sodium Sustained-Release Tablet Formulations in Fasting, Healthy Chinese Male Volunteers()

BACKGROUND: Diclofenac is a nonsteroidal anti-inflammatory drug used for the treatment of patients with osteoarthritis. OBJECTIVES: Our primary objective was to compare bioavailability and tolerability of a generic sustained-release tablet with the established reference sustained-release tablet of diclofenac sodium in a fasting, healthy Chinese male population. METHODS: A randomized, open-label, single- and multiple-dose study design was used. After the single dose, volunteers received diclofenac sodium sustained-release tablet once daily for 5 days. In the single-dose phase, blood samples were collected from 0 to 36 hours after drug administration. In the multiple-dose phase, samples were obtained before drug administration at 8:00 am on Days 3 and 4 to determine C(min,ss) of diclofenac sodium; on Day 5, samples were collected from 0 to 36 hours. Adverse events were monitored via subject interview, vital signs, and blood sampling. RESULTS: Twenty-four Chinese male volunteers were enrolled. The pharmacokinetic parameters (mean [SD]) for diclofenac after single dose of 75 and 100 mg were: C(max) 473.5 [179.5] and 546.6 [154.9] ng/mL; AUC(0–∞) 3841.2 [1402.3], and 5019.1 [2,314.0] ng·h/mL; T(max) 4.9 [2.4], and 4.3 [2.2] hours; t(1/2) 5.9 [2.5], and 6.0 [2.2] hours. Mean [SD] values after multiple doses of 75 and 100 mg were: C(max,ss) 525.6 [127.4] and 650.5 [167.0] ng/mL, C(min,ss) 33.9 [20.9] and 62.9 [34.9] ng/mL, AUC(ss) 4316.3 [633.0] and 5335.1 [1291.9] ng·h/mL, C(av,ss) 179.8 [26.4] and 222.3 [53.8] ng/mL, T(max) 5.1 [1.8] and 4.5 [0.9] hours and t(1/2) 5.2 [2.9] and 5.5 [2.8] hours, respectively. CONCLUSIONS: This diclofenac sodium 75 mg tablet has features compatible with the 100 mg sustained-release tablet and appeared to be well tolerated. ClinicalTrials.gov identifier: 2010L01969