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The pharmacokinetic profiles of naproxen in blood and synovial fluid (SF) following topical and i.v. bolus administration in dogs, and the local tissue disposition of the drug following topical and oral administration in rats, were investigated to assess the feasibility of topical delivery of naproxen for local and systemic effects. The naproxen gel in poloxamer 407 (PF‐127) was applied on the stifle joint of dogs, and serum and synovial fluid samples were collected. For local tissue disposition studies, the naproxen gel was applied on the dorsal skin in rats, and blood, skin, and muscle samples were taken at 3, 6, and 12 h postdose after removing the residual gel from the skin. Steady state serum concentrations occurred at ∼20 h after topical doses and lasted for the next ∼30 h in dogs. Similar SF–serum concentration ratios of naproxen were found between i.v. (0·61±0·16) and topical (0·55±0·14) routes of administration. Following the i.v. dose, the half‐life of naproxen in SF (∼60 h) was significantly longer than that in serum (∼40 h). The bioavailability of naproxen in the topical gel was ∼2% of the applied dose in dogs. A large accumulation of drug in the epidermis, dermis, and muscle tissue beneath the gel application site was found in rats. Isopropyl myristate (IPM) significantly increased the systemic absorption as well as the concentrations of naproxen in the underlying dermis and muscle tissues, but exerted little effect on the disposition of naproxen in the epidermis. © 1997 John Wiley & Sons, Ltd.

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