Evaluation of dose linearity in the systemic availability and pharmacokinetics of topically administered diclofenac: A 14C-microdosing study in healthy volunteers.
Drug metabolism and disposition: the biological fate of chemicals July 1, 2025 Severin Mairinger, Mihye Kwon, Martin Bauer et al.
Systemic absorption of a topically applied drug may not be dose-linear, limiting the usefulness of microdosing to predict therapeutic-dose exposure. In a crossover study of eight healthy participants, a topical microdose of diclofenac (62 μg) resulted in a higher fraction absorbed (0.48%) compared with a therapeutic dose (120 mg, 0.13%), a 3.79-fold difference. Intravenous dosing showed dose-linear disposition. Concentrations in subcutaneous tissue microdialysates were low and variable regardless of dose. The findings indicate that microdosing may not accurately predict the systemic availability of certain topical drugs at therapeutic doses.