title: Pharmacokinetics and pharmacodynamics of once- and twice-daily multiple-doses of canagliflozin, a selective inhibitor of sodium glucose co-transporter 2, in healthy participants.
abstract: OBJECTIVE
  Assess the steady-state pharmacokinetics, pharmacodynamics and safety of once-daily (q.d.) versus twice-daily (b.i.d.) dosing with canagliflozin at the same total daily doses of 100 and 300 mg in healthy participants.
  
  
  METHODS
  34 participants (17 in each cohort) were enrolled in this single-center, open-label, multiple-dose, 2-cohort, 2-way crossover study. Participants in each cohort received a total daily dose of either 100 or 300 mg canagliflozin for 5 days with q.d. then b.i.d. dosing or vice versa. Pharmacokinetics and pharmacodynamics were assessed on day 5 of each period.
  
  
  RESULTS
  The canagliflozin Cmax,ss of 100 and 300 mg q.d. dosing were higher by 66% and 72% than corresponding morning Cmax,ss of the 50 mg and 150 mg b.i.d. regimen, respectively. The geometric mean ratios (90% CI) of b.i.d./q.d. for AUC0-24h,ss at total doses of 100 and 300 mg were 97.08 (94.08; 99.62) and 99.32 (94.71; 104.16) respectively. Median tmax and mean t1/2 were independent of dose and regimen. Mean (SE) 24-h mean renal glucose threshold values for b.i.d. and q.d. regimens were 59.2 (1.03) and 60.2 (1.03) mg/dL for the 100 mg daily doses and 51.0 (1.04) and 52.5 (1.04) mg/dL for the 300 mg daily doses. Mean (SE) values of 24-h urinary glucose excretion for b.i.d. and q.d. regimens were 52.8 (1.94) and 48.6 (1.94) g for the 100 mg daily doses and 58.6 (3.81) and 57.8 (3.81) g for the 300 mg daily doses. Both doses were safe and well tolerated.
  
  
  CONCLUSIONS
  Pharmacokinetics and pharmacodynamics of canagliflozin administered q.d. relative to b.i.d. at the same 100 and 300 mg total daily doses were comparable. Overall, canagliflozin was well tolerated.
authors.forename: Damayanthi
authors.initials: D
authors.lastname: Devineni
authors.forename: David
authors.initials: D
authors.lastname: Polidori
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Curtin
authors.forename: Joseph
authors.initials: J
authors.lastname: Murphy
authors.forename: Shean-Sheng
authors.initials: SS
authors.lastname: Wang
authors.forename: Hans
authors.initials: H
authors.lastname: Stieltjes
authors.forename: Ewa
authors.initials: E
authors.lastname: Wajs
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D000068896:Canagliflozin; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D005260:Female; D005960:Glucosides / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D064368:Healthy Volunteers; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008954:Models, Biological; D018570:Risk Assessment; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013876:Thiophenes / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D005960:Glucosides; D007004:Hypoglycemic Agents; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013876:Thiophenes; D000068896:Canagliflozin