PMID- 27981717
OWN - NLM
STAT- MEDLINE
DCOM- 20171102
LR  - 20171129
IS  - 1463-1326 (Electronic)
IS  - 1462-8902 (Linking)
VI  - 19
IP  - 4
DP  - 2017 Apr
TI  - Effect of varying degrees of renal impairment on the pharmacokinetics and 
      tolerability of taspoglutide.
PG  - 537-544
LID - 10.1111/dom.12850 [doi]
AB  - AIM: To evaluate single-dose pharmacokinetics and tolerability of taspoglutide in 
      people with varying degrees of renal impairment and matched healthy participants. 
      METHODS: Participants in the present study were people with mild renal impairment 
      (n = 10), moderate impairment (n = 10), severe impairment (n = 9), and a matched 
      healthy control group (n = 10). Participants received a single subcutaneous 
      injection of taspoglutide (10 mg) on day 1. Plasma and urine drug concentration, 
      antibody formation, vital signs, ECGs and routine laboratory variables were 
      measured frequently and adverse events (AEs) were monitored for 9 weeks. RESULTS: 
      Taspoglutide exposure was higher among participants with moderate and severe 
      renal impairment compared with participants with normal renal function. Mean 
      AUC(last) was 13% and 38% higher in participants with moderate and severe renal 
      impairment, respectively compared with participants with normal renal function. 
      Likewise, mean peak plasma concentration (C(max) ) was 57% and 93% higher in 
      participants with moderate and severe renal function impairment, respectively, 
      compared with participants with normal renal function. Linear regression analyses 
      showed a statistically significant inverse relationship between taspoglutide 
      exposure parameters (AUC and C(max) ) and creatinine clearance. Higher incidences 
      of gastrointestinal (GI) AEs were reported in participants with severe renal 
      impairment. CONCLUSION: Renal impairment altered the pharmacokinetics of 
      taspoglutide. The degree of renal impairment was associated with an increased 
      exposure to taspoglutide and an increased risk of GI AEs.
CI  - (c) 2016 John Wiley & Sons Ltd.
FAU - Giraudon, Mylene
AU  - Giraudon M
AD  - F. Hoffmann-La Roche AG, Basel, Switzerland.
FAU - Sturm, Stefan
AU  - Sturm S
AD  - F. Hoffmann-La Roche AG, Basel, Switzerland.
FAU - Lambert, Nathalie
AU  - Lambert N
AD  - Novartis Pharma AG, Basel, Switzerland.
FAU - Niggli, Markus
AU  - Niggli M
AD  - F. Hoffmann-La Roche AG, Basel, Switzerland.
FAU - Brumm, Jochen
AU  - Brumm J
AD  - Genentech, South San Francisco, California.
FAU - Mangold, Bernhard
AU  - Mangold B
AD  - F. Hoffmann-La Roche AG, Basel, Switzerland.
FAU - Schmitt, Christophe
AU  - Schmitt C
AD  - F. Hoffmann-La Roche AG, Basel, Switzerland.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170127
PL  - England
TA  - Diabetes Obes Metab
JT  - Diabetes, obesity & metabolism
JID - 100883645
RN  - 0 (Peptides)
RN  - 2PHK27IP3B (taspoglutide)
RN  - AYI8EX34EU (Creatinine)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antibody Formation/drug effects
MH  - Creatinine/analysis
MH  - Female
MH  - Gastrointestinal Diseases/chemically induced
MH  - Humans
MH  - Kidney/drug effects/metabolism
MH  - Kidney Function Tests
MH  - Linear Models
MH  - Male
MH  - Metabolic Clearance Rate/drug effects
MH  - Middle Aged
MH  - Peptides/*pharmacokinetics
MH  - Renal Insufficiency/*metabolism
OTO - NOTNLM
OT  - GLP-1 agonist
OT  - incretin
OT  - pharmacokinetics
OT  - renal function
OT  - taspoglutide
OT  - tolerability
EDAT- 2016/12/17 06:00
MHDA- 2017/11/03 06:00
CRDT- 2016/12/17 06:00
PHST- 2016/09/26 00:00 [received]
PHST- 2016/12/01 00:00 [revised]
PHST- 2016/12/08 00:00 [accepted]
PHST- 2016/12/17 06:00 [pubmed]
PHST- 2017/11/03 06:00 [medline]
PHST- 2016/12/17 06:00 [entrez]
AID - 10.1111/dom.12850 [doi]
PST - ppublish
SO  - Diabetes Obes Metab. 2017 Apr;19(4):537-544. doi: 10.1111/dom.12850. Epub 2017 
      Jan 27.