PMID- 19476474
OWN - NLM
STAT- MEDLINE
DCOM- 20101210
LR  - 20220408
IS  - 1463-1326 (Electronic)
IS  - 1462-8902 (Linking)
VI  - 11
IP  - 8
DP  - 2009 Aug
TI  - Pharmacokinetics, pharmacodynamics and tolerability of multiple oral doses of 
      linagliptin, a dipeptidyl peptidase-4 inhibitor in male type 2 diabetes patients.
PG  - 786-94
LID - 10.1111/j.1463-1326.2009.01046.x [doi]
AB  - AIMS: To investigate the safety, tolerability, pharmacokinetic and 
      pharmacodynamic properties of multiple oral doses of the dipeptidyl peptidase-4 
      (DPP-4) inhibitor linagliptin (BI 1356) in patients with type 2 diabetes 
      mellitus. METHODS: Forty-seven male type 2 diabetic patients received linagliptin 
      1, 2.5, 5 or 10 mg, or placebo, once daily for 12 days. RESULTS: Linagliptin 
      exposure [area under the plasma concentration-time curve and maximum plasma 
      concentration (Cmax)] increased less than proportionally with dose. Accumulation 
      half-life was short (8.6-23.9 h), resulting in rapid attainment of steady state 
      (2-5 days) and little accumulation (range: 1.18-2.03). The long terminal 
      half-life (113-131 h) led to a sustained inhibition of DPP-4 activity. Renal 
      excretion was below 1% on day 1 in all dose groups. Inhibition of plasma DPP-4 
      activity correlated well with linagliptin plasma concentrations, resulting in 
      DPP-4 inhibition >90% in the two highest dose groups; even 24 h postdose, DPP-4 
      inhibition was >80%. Following an oral glucose tolerance test, 24 h after the 
      last dose, statistically significant reductions of glucose excursions were 
      observed with linagliptin (2.5, 5 and 10 mg doses) compared with placebo. 
      Linagliptin was well tolerated. The frequency of adverse events (AEs) was not 
      higher with linagliptin (54%) than with placebo (75%). No serious AEs and no 
      episodes of hypoglycaemia were reported. CONCLUSIONS: In type 2 diabetic 
      patients, multiple rising doses of linagliptin were well tolerated and resulted 
      in significant improvements of glucose parameters. Together with the favourable 
      pharmacokinetics, these results confirm the unique profile of linagliptin in the 
      DPP-4 inhibitor class.
FAU - Heise, T
AU  - Heise T
AD  - Profil Institut fur Stoffwechselforschung GmbH, Hellersbergstrasse, Neuss, 
      Germany.
FAU - Graefe-Mody, E U
AU  - Graefe-Mody EU
FAU - Huttner, S
AU  - Huttner S
FAU - Ring, A
AU  - Ring A
FAU - Trommeshauser, D
AU  - Trommeshauser D
FAU - Dugi, K A
AU  - Dugi KA
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
DEP - 20090519
PL  - England
TA  - Diabetes Obes Metab
JT  - Diabetes, obesity & metabolism
JID - 100883645
RN  - 0 (Dipeptidyl-Peptidase IV Inhibitors)
RN  - 0 (Purines)
RN  - 0 (Quinazolines)
RN  - 3X29ZEJ4R2 (Linagliptin)
RN  - EC 3.4.14.5 (Dipeptidyl Peptidase 4)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Area Under Curve
MH  - Diabetes Mellitus, Type 2/*drug therapy
MH  - Dipeptidyl Peptidase 4/blood
MH  - Dipeptidyl-Peptidase IV Inhibitors/*administration & dosage/adverse 
      effects/*pharmacokinetics
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Half-Life
MH  - Humans
MH  - Linagliptin
MH  - Male
MH  - Metabolic Clearance Rate
MH  - Middle Aged
MH  - Purines/administration & dosage/*adverse effects/*pharmacokinetics
MH  - Quinazolines/administration & dosage/*adverse effects/*pharmacokinetics
MH  - Young Adult
EDAT- 2009/05/30 09:00
MHDA- 2010/12/14 06:00
CRDT- 2009/05/30 09:00
PHST- 2009/05/30 09:00 [entrez]
PHST- 2009/05/30 09:00 [pubmed]
PHST- 2010/12/14 06:00 [medline]
AID - DOM1046 [pii]
AID - 10.1111/j.1463-1326.2009.01046.x [doi]
PST - ppublish
SO  - Diabetes Obes Metab. 2009 Aug;11(8):786-94. doi: 
      10.1111/j.1463-1326.2009.01046.x. Epub 2009 May 19.