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Systemic Bioavailability of Topical Diclofenac Sodium Gel 1% Versus Oral Diclofenac Sodium in Healthy Volunteers
Author(s) -
Kienzler JeanLuc,
Gold Morris,
Nollevaux Fabrice
Publication year - 2010
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270009336234
Subject(s) - diclofenac , diclofenac sodium , bioavailability , pharmacology , pharmacokinetics , medicine , oral administration , crossover study , chemistry , placebo , alternative medicine , pathology
Systemic bioavailability and pharmacodynamics of topical diclofenac sodium gel 1% were compared with those of oral diclofenac sodium 50‐mg tablets. In a randomized, 3‐way crossover study, healthy volunteers (n = 40) received three 7‐day diclofenac regimens: (A) 16 g gel applied as 4 g to 1 knee 4 times daily (4 g on surface area 400 cm 2 ), (B) 48 g gel applied as 4 g per knee 4 times daily to 2 knees plus 2 g gel per hand applied 4 times daily to 2 hands (12 g on 1200 cm 2 ), and (C) 150 mg oral diclofenac applied as 50‐mg tablets 3 times daily. Thirty‐nine participants completed all 3 regimens. Systemic exposure was greater with oral diclofenac (AUC 0–24 , 3890 ± 1710 ng·h/mL) than with topical treatments A (AUC 0–24 , 233 ± 128 ng·h/mL) and B (AUC 0–24 , 807 ± 478 ng·h/mL). Oral diclofenac inhibited platelet aggregation, cyclooxygenase‐1 (COX‐1), and COX‐2. Topical diclofenac did not inhibit platelet aggregation and inhibited COX‐1 and COX‐2 less than oral diclofenac. Treatment‐related adverse events were mild and limited to application site reactions with diclofenac sodium gel 1% (n = 4) and gastrointestinal reactions with oral diclofenac (n = 3). Systemic exposure with diclofenac sodium gel 1% was 5‐ to 17‐fold lower than with oral diclofenac. Systemic effects with topical diclofenac were less pronounced.