Bioavailability Pharmacokinetics and Transepidermal Water Loss of Short Contact Tazarotene Lotion 0.1 Versus Tazarotene (Tazorac®) Cream 0.1

摘要

>Objective: Two clinical studies were conducted to 1) assess the pharmacokinetic (PK) properties of tazarotene and tazarotenic acid in DFD-03 lotion (a 1-minute, short-contact formulation for the topical treatment of acne vulgaris) and tazarotene cream 0.1% and 2) to evaluate transepidermal water loss (TEWL) with DFD-03 lotion, tazarotene gel (0.1%), or vehicle. >Design: The PK study included a single-center, randomized, multiple-dose, laboratory-blinded, open-label, parallel-design, and the TEWL study included a multiple-dose, within-subject comparison design. >Participants: The PK study included healthy adult men aged 18 to 40 years (n=43), and the TEWL study included healthy adults, male or female, aged 18 to 40 years (n=24). >Measurements: PK was assessed via Cmax, AUC0-12, AUC0-24, Tmax, Cmin, Tmin, and fluctuation. TEWL was assessed via evaporimetry. >Results: Tazarotene levels were very low due to rapid esterase hydrolysis to the primary active metabolite, tazarotenic acid. Tazarotenic acid AUC0-24 ratios (%) were at least two times higher when the test product was applied twice daily (Treatment-1) versus once daily (Treatment-2) on Days 7 and 14 (268.73% and 254.42%, respectively). Tazarotenic acid AUC0-24 ratios (%) were nearly 100 percent for Treatment-1 versus once-daily tazarotene cream 0.1% (Treatment-3) (99.36% and 83.21%, on Days 7 and 14, respectively). Starting on Day 7, DFD-03 lotion TEWL readings were significantly greater than vehicle (p≤0.05), except for on one study day. DFD-03 lotion TEWL readings were numerically greater (nonsignificant) than tazarotene gel. >Conclusion: DFD-03 lotion was well-tolerated, increased TEWL when applied twice daily for one minute, and had a PK profile with similar overall exposure as compared with commercially available tazarotene formulations applied once daily for 12 hours.