title: Bioequivalence of Linagliptin 5 mg once daily and 2.5 mg twice daily: pharmacokinetics and pharmacodynamics in an open-label crossover trial.
abstract: Linagliptin is an oral antihyperglycemic drug that acts by inhibiting the dipeptidyl peptidase-4 enzyme. A 5-mg once-daily regimen is available, but an alternative regimen was needed for twice-daily fixed-dose combinations. Although linagliptin has non-linear pharmacokinetics, simulation suggested 2.5 mg twice-daily would provide bioequivalent exposure and comparable plasma dipeptidyl peptidase-4 inhibition to 5 mg once-daily.This crossover study compared steady-state pharmacokinetics and pharmacodynamics of linagliptin 5 mg once-daily and 2.5 mg twice-daily, both administered for 7 days.In total, 16 healthy volunteers entered the study, and 15 completed both treatment periods. Exposure over 24-h at steady state (AUC0-24,ss) was similar for linagliptin 5 mg once-daily and 2.5 mg twice-daily (132 vs. 124 nmol · h/L), and the 90% confidence interval of the adjusted geometric mean ratio of AUC0-24,ss was well within the acceptance range for bioequivalence (ratio 93.9%; 90% confidence interval 89.5, 98.5). Median dipeptidyl peptidase-4 inhibition over a 24-h interval at steady state was 85.9% with linagliptin 5 mg once-daily and 86.5% with 2.5 mg twice-daily, and median dipeptidyl peptidase-4 inhibition values were approximately 80.0% at trough. Most subjects had no adverse events and there were no serious adverse events.Linagliptin 5 mg once-daily and 2.5 mg twice-daily provided bioequivalent exposure and similar inhibition of dipeptidyl peptidase-4 over the whole dosing interval.
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Friedrich
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Jungnik
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Retlich
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Ring
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Meinicke
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D018592:Cross-Over Studies; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D000069476:Linagliptin; D008297:Male; D008875:Middle Aged; D011687:Purines / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D011687:Purines; D011799:Quinazolines; D000069476:Linagliptin; D018819:Dipeptidyl Peptidase 4