title: [Development of transdermal formulation of tulobuterol for the treatment of bronchial asthma].
abstract: beta 2-Adrenergic agonists have been widely used to treat patients with asthma. Usually, oral dosage forms of beta 2-agonists have been used, but side effects such as palpitation and tremor have been reported because of excessive serum levels around Tmax. It is said that circadian variations exist in the manifestation of asthma with maximum incidence of asthma attacks in early morning at around 4 a.m., the so-called morning dip. Chronotherapy for asthma based on circadian rhythm should be more efficient and have a lower frequency of side effects. Accordingly we developed a transdermal delivery system of the beta 2-agonist tulobuterol adapted to the circadian rhythm. The system is designed to administer the appropriate dose of the drug at an optimal time using the so-called Crystal Reservoir System. The superiority of the transdermal formulation of tulobuterol over the current therapy using oral formulations of beta 2-stimulants was indicated by its excellent pharmacokinetic profile, and confirmed by the results of clinical trials. This formulation is the first transdermal chrono-delivery system reported anywhere in the world, and is expected to provide more effective and safe treatment of asthma and related diseases not only in adults, but also especially in children.
authors.affiliation: Hokuriku Seiyaku Co., Ltd., 37-1-1, Inokuchi, Katsuyama, Fukui 911-8555, Japan and NITTO DENKO CORPORATION, 1-1-2, Shimohozumi, Ibaraki, Osaka 567-8680, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Kato
authors.forename: Osamu
authors.initials: O
authors.lastname: Nagata
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamazaki
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Suzuki
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Nakano
mesh_terms: D000279:Administration, Cutaneous; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000493:pharmacokinetics; D001249:Asthma / Q000188:drug therapy*; D019454:Chronotherapy; D002986:Clinical Trials as Topic; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D013726:Terbutaline / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D000318:Adrenergic beta-Agonists; C010809:tulobuterol; D013726:Terbutaline