Systemic absorption of ciclopirox was determined in 5 patients with dermatophytic onychomycoses, after application of PENLAC (ciclopirox topical solution) ® NAIL LACQUER (ciclopirox) Topical Solution, 8%, to all 20 digits and adjacent 5 mm of skin once daily for six months. Random serum concentrations and 24 hour urinary excretion of ciclopirox were determined at two weeks and at 1, 2, 4 and 6 months after initiation of treatment and 4 weeks post-treatment. In this study, ciclopirox serum levels ranged from 12-80 ng/mL. Based on urinary data, mean absorption of ciclopirox from the dosage form was < 5% of the applied dose. One month after cessation of treatment, serum and urine levels of ciclopirox were below the limit of detection.
The continued search for new and less toxic antifungals led to the discovery of the azoles several decades later with the first release in the early 1980s. However, in the 1990s, new discoveries of both fluconazole and itraconazole displayed a broader spectrum of antifungal activity. Eventually, these agents became subject to a number of clinically important limitations related to their development of resistance, the induction of hazardous drug interactions and their performance as they moved throughout the body and their toxicity. ( 17 )