Pharmacokinetics of single and multiple oral doses of 5 mg linagliptin in healthy Chinese volunteers.
OBJECTIVE
To investigate the pharmacokinetic and safety profile of linagliptin after single and multiple doses in healthy Chinese volunteers.


METHODS
Men and women (n = 12) aged 18 - 45 years with body mass index 19 - 24 kg/m2 received a single 5-mg dose of linagliptin on Day 1, followed by 7-day washout and 6 consecutive days of once-daily administration. Vital signs, electrocardiogram, routine laboratory tests, urinalysis, and adverse events were recorded. Blood and urine analytes were measured by HPLC/MS/MS.


RESULTS
Linagliptin was rapidly absorbed; median time to maximum concentration was 1.75 h for single dose and 1.5 h at steady-state. Maximum plasma drug concentration (Cmax) after single dose was 4.9 ng/ml (10.4 nM), with a geometric coefficient of variation (gCV) 46%. The corresponding geometric mean area under the plasma concentrationtime curve (AUC) was 71 ng×h ml-1 (150 nmol×h l-1, gCV 25%). At steady-state, Cmax and AUC were 6.7 ng/ml (14.1 nM, gCV 49%) and 96 nmol×h l-1 (204 nmol×h l-1, gCV 25%). An accumulation half-life of ~ 11.5 h (gCV 46.9%) was calculated. Renal excretion of linagliptin was low and < 8% of administered dose at steady-state (< 2% at Day 1). Single and multiple daily oral doses of 5 mg linagliptin were safe and well tolerated. No adverse events or clinically significant changes in laboratory tests, vital signs, or physical examination were reported.


CONCLUSIONS
Linagliptin demonstrated a favorable safety profile in healthy Chinese volunteers, with a pharmacokinetic profile that was similar to that observed previously in subjects of Japanese, Caucasian, or African American origin.
Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany. christian.friedrich@boehringer-ingelheim.com
Christian
C
Friedrich
Xiaojin
X
Shi
Peter
P
Zeng
Arne
A
Ring
Hans-Juergen
HJ
Woerle
Sanjay
S
Patel
D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D000069476:Linagliptin; D008297:Male; D011687:Purines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011799:Quinazolines / Q000008:administration & dosage / Q000493:pharmacokinetics*
D054873:Dipeptidyl-Peptidase IV Inhibitors; D011687:Purines; D011799:Quinazolines; D000069476:Linagliptin