title: Evaluation of change in the skin concentration of tazarotene and betamethasone dipropionate based on drug-drug interaction for transdermal drug delivery in miniature pig.
abstract: 1. The present study was designed to investigate drug-drug interaction in a new combination cream which contains both tazarotene (TZRT) and betamethasone dipropionate (BTMSDP) by comparing the pharmacokinetic (PK) behaviors of TZRT, BTMSDP, and their major metabolites, tazarotenic acid (TZRTAC) and betamethasone (BTMS) with those in the commonly prescribed TZRT gel and BTMSDP cream. 2. The trial was performed on six Bama mini-pigs. The different regions on the back side of each pig were randomly assigned to one of three treatment groups: TZRT 0.05% gel, BTMSDP 0.05% cream, and combination cream. The stratum corneum and epidermis-dermis samples were collected at various times after drug administration and analyzed for TZRT, TZRTAC, BTMSDP, and BTMS by LC-MS/MS. Compared with TZRT gel alone, TZRT + BTMSDP did not significantly change the PK profiles of TZRT; neither did BTMSDP + TZRT significantly change the PK profiles of BTMSDP, compared with the BTMSDP cream alone. In addition, the concentrations of TZRTAC and BTMS in most samples were below the lower limit of quantitation (LLOQ). 3. The results suggest that there was no significant drug-drug interaction trend between TZRT and BTMSDP in the process of transdermal permeation of combination cream into the stratum corneum and epidermis-dermis of mini-pigs.
authors.affiliation: Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University , Nanjing , China .
authors.forename: Biao
authors.initials: B
authors.lastname: Yu
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Ma
authors.forename: Linwen
authors.initials: L
authors.lastname: Yuan
authors.forename: Dingding
authors.initials: D
authors.lastname: Chen
authors.forename: Jin
authors.initials: J
authors.lastname: Yang
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D001623:Betamethasone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D020405:Dermis; D016503:Drug Delivery Systems; D004347:Drug Interactions; D004817:Epidermis; D005782:Gels; D009539:Nicotinic Acids / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D009824:Ointments; D012867:Skin / Q000187:drug effects*; D013552:Swine; D013556:Swine, Miniature; D013997:Time Factors; D012176:Retinoids
chemical_list: D001623:Betamethasone; D005782:Gels; D009539:Nicotinic Acids; D009824:Ointments; C086827:tazarotene; D012176:Retinoids; C011175:betamethasone-17,21-dipropionate
keywords: Betamethasone dipropionate cream; combination cream; drug–drug interaction; psoriasis; skin homogenate; tazarotene gel; tissue distribution