The mechanism of action of diclofenac sodium in the treatment of actinic keratoses (AK) is unknown.
The contribution to efficacy of individual components of the vehicle has not been established.
When Solaraze® is applied topically, diclofenac is absorbed into the epidermis. In a study in patients with compromised skin (mainly atopic dermatitis and other dermatitic conditions) of the hands, arms or face, approximately 10% of the applied dose (2 grams of 3% gel over 100 cm2) of diclofenac was absorbed systemically in both normal and compromised epidermis after seven days, with four times daily applications.
After topical application of 2 g Solaraze® three times daily for six days to the calf of the leg in healthy subjects, diclofenac could be detected in plasma. Mean bioavailability parameters were AUC0-t 9±19 ng/hr/mL (mean±SD) with a Cmax of 4±5 ng/mL and a Tmax of 4.5±8 hours. In comparison, a single oral 75 mg dose of diclofenac (Voltaren®)Voltaren® is a registered trademark of Novartis. produced an AUC of 1600 ng/hr/mL. Therefore, the systemic bioavailability after topical application of Solaraze® is lower than after oral dosing.
Blood drawn at the end of treatment from 60 patients with AK lesions treated with Solaraze® in three adequate and well-controlled clinical trials was assayed for diclofenac levels. Each patient was administered 0.5 g of Solaraze® Gel twice a day for up to 105 days. There were up to three 5 cm × 5 cm treatment sites per patient on the face, forehead, hands, forearm, and scalp. Serum concentrations of diclofenac were, on average, at or below 20 ng/mL. These data indicate that systemic absorption of diclofenac in patients treated topically with Solaraze® is much lower than that occurring after oral daily dosing of diclofenac sodium.
No information is available on the absorption of diclofenac when Solaraze® is used under occlusion.
Diclofenac binds tightly to serum albumin. The volume of distribution of diclofenac following oral administration is approximately 550 mL/kg.
Biotransformation of diclofenac following oral administration involves conjugation at the carboxyl group of the side chain or single or multiple hydroxylations resulting in several phenolic metabolites, most of which are converted to glucuronide conjugates. Two of these phenolic metabolites are biologically active, however to a much smaller extent than diclofenac. Metabolism of diclofenac following topical administration is thought to be similar to that after oral administration. The small amounts of diclofenac and its metabolites appearing in the plasma following topical administration makes the quantification of specific metabolites imprecise.
Diclofenac and its metabolites are excreted mainly in the urine after oral dosing. Systemic clearance of diclofenac from plasma is 263±56 mL/min (mean±SD). The terminal plasma half-life is 1-2 hours. Four of the metabolites also have short terminal half-lives of 1-3 hours.