Clinical Pharmacokinetics and Safety of a 10% Aminolevulinic Acid Hydrochloride Nanoemulsion Gel (BF‐200 ALA) in Photodynamic Therapy of Patients Extensively Affected With Actinic Keratosis: Results of 2 Maximal Usage Pharmacokinetic Trials

The nanoemulsion‐based 10% aminolevulinic acid (ALA) hydrochloride gel BF‐200 ALA optimizes epidermal penetration of its active ingredient and is approved for topical photodynamic therapy (PDT) for the treatment of actinic keratosis in the United States and Europe. To characterize systemic absorption from dermal application during PDT, ALA and its key active metabolite protoporphyrin IX (PpIX) were analyzed in 2 maximal usage pharmacokinetic trials (MUsT) in patients severely affected with actinic keratosis. The primary objective of both MUsTs was to assess baseline‐adjusted plasma concentration–time curves for ALA and PpIX after a single PDT treatment applying either 2 g (1 tube) of BF‐200 ALA on the face (MUsT‐1) or applying 6 g (3 tubes) of BF‐200 ALA on the face/scalp or body periphery (MUsT‐2), to 20 or 60 cm(2), respectively. All PDTs were performed using red light at around 635 nm wavelength. Safety and tolerability were documented along with pharmacokinetics. In both MUsTs, ALA plasma concentrations were transiently increased to a maximum concentration at about 2.5 to 3.3 times above endogenous baseline with time to maximum concentration at ≈3 hours after dosing. Plasma levels subsequently returned to baseline within 10 hours after dosing. Overall baseline‐adjusted mean area under the baseline‐adjusted plasma concentration‐time curve from time zero to the last sampling time point at which the concentration was at or above the lower limit of quantification ranged from 142.8 to 146.2, indicating that a similar, minor fraction of topical ALA is systemically absorbed under both dosing regimens. Systemic PpIX exposure after administration of either dose of BF‐200 ALA was equally minimal. Application site skin reactions were treatment area size‐related, albeit transient and consistent with the known safety profile of BF‐200 ALA.