title: Safety, tolerability, pharmacokinetics and pharmacodynamics of single doses of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in healthy Japanese subjects.
abstract: This randomized, placebo-controlled within dose groups, double-blind, single rising dose study investigated the safety, tolerability, pharmacokinetics and pharmacodynamics of 1 mg to 100 mg doses of empagliflozin in 48 healthy Japanese male subjects. Empagliflozin was rapidly absorbed, reaching peak levels in 1.25 to 2.50 h; thereafter, plasma concentrations declined in a biphasic fashion, with mean terminal elimination half-life ranging from 7.76 to 11.7 h. Increase in empagliflozin exposure was proportional to dose. Oral clearance was dose independent and ranged from 140 to 172 mL/min. In the 24 h following 100 mg empagliflozin administration, the mean (%CV) amount of glucose excreted in urine was 74.3 (17.1) g. The amount and the maximum rate of glucose excreted via urine increased with dose of empagliflozin. Nine adverse events, all of mild intensity, were reported by 8 subjects (7 with empagliflozin and 1 with the placebo). No hypoglycemia was reported. In conclusion, 1 mg to 100 mg doses of empagliflozin had a good safety and tolerability profile in healthy Japanese male subjects. Exposure to empagliflozin was dose proportional. The amount and rate of urinary glucose excretion were higher with empagliflozin than with the placebo, and increased with empagliflozin dose.
authors.affiliation: Clinical PK/PD Group, Medical Development Division, Nippon Boehringer Ingelheim Co., Ltd., Kobe, Japan. sarasina@kaw.boehringer-ingelheim.com
authors.forename: Akiko
authors.initials: A
authors.lastname: Sarashina
authors.forename: Kazuki
authors.initials: K
authors.lastname: Koiwai
authors.forename: Leo J
authors.initials: LJ
authors.lastname: Seman
authors.forename: Norio
authors.initials: N
authors.lastname: Yamamura
authors.forename: Atsushi
authors.initials: A
authors.lastname: Taniguchi
authors.forename: Takahiro
authors.initials: T
authors.lastname: Negishi
authors.forename: Shogo
authors.initials: S
authors.lastname: Sesoko
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Woerle
authors.forename: Klaus A
authors.initials: KA
authors.lastname: Dugi
mesh_terms: D044466:Asian People; D001559:Benzhydryl Compounds / Q000493:pharmacokinetics* / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004311:Double-Blind Method; D005947:Glucose / Q000378:metabolism; D005960:Glucosides / Q000493:pharmacokinetics* / Q000494:pharmacology; D006029:Glycosuria / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors
chemical_list: D001559:Benzhydryl Compounds; D005960:Glucosides; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C570240:empagliflozin; D005947:Glucose