Concentration-dependent plasma protein binding of the novel dipeptidyl peptidase 4 inhibitor BI 1356 due to saturable binding to its target in plasma of mice, rats and humans

Journal of Pharmacy and Pharmacology

Volumn 61, Issue 1, 2009, Pages 55-62

  Fuchs, Holger ^a   Tillement, Jean Paul ^b   Urien, Saik ^b   Greischel, Andreas ^a   Roth, Willy ^a  

^a BOEHRINGER INGELHEIM PHARMA GMBH AND CO KG   (Germany)

^b Paris Descartes University   (France)

Author keywords

BI 1356; Dipeptidyl peptidase 4 inhibitor; Pharmacokinetics; Plasma protein binding; Type 2 diabetes

Indexed keywords

8 (3 AMINO 1 PIPERIDINYL) 7 (2 BUTYNYL) 3 METHYL 1 (4 METHYL 2 QUINAZOLINYLMETHYL)XANTHINE; DIPEPTIDYL PEPTIDASE IV;

ARTICLE; BINDING AFFINITY; BINDING KINETICS; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG DOSE COMPARISON; DRUG ELIMINATION; DRUG PROTEIN BINDING; DRUG URINE LEVEL; ENZYME INHIBITOR INTERACTION; FEMALE; HUMAN; ISOTOPE LABELING; KNOCKOUT MOUSE; MALE; MOUSE; NONHUMAN; NORMAL HUMAN; PLASMA; RAT; SINGLE DRUG DOSE; SPECIES COMPARISON;

EID: 58149247983     PISSN: 00223573     EISSN: None     Source Type: Journal    
DOI: 10.1211/jpp.61.01.0008     Document Type: Article

References (20)

1. Eckhardt M et al. 8-(3-(R)-aminopiperidin-1-yl)-7-but-2-ynyl-3- methyl-1-(4-methy1-quinazolin-2-ylmethyl)-3,7-dihydropurine-2,6-dione (BI 1356), a highly potent, selective, long-acting, and orally bioavailable DPP-4 inhibitor for the treatment of type 2 diabetes. J Med Chem 2007; 50: 6450-6453.
2. Mentlein R. Cell-surface peptidases. Int Rev Cytol 2004; 235: 165-213.
3. Todd JF, Bloom SR. Incretins and other peptides in the treatment of diabetes. Diabetic Med 2007; 24: 223-232.
4. Ahrén B. Enhancement or prolongation of GLP-1 activity as a strategy for treatment of type 2 diabetes. Drug Discov Today Ther Strategies 2004; 1: 207-212.
5. Tillement JP et al. The binding of drugs to blood plasma macromolecules: recent advances and therapeutic significance. Adv Drug Res 1984; 13: 60-90.
6. Hirayama M et al. Pharmacokinetics of RU44403, an active form of newly developed angiotensin-converting enzyme inhibitor (RU44570) in the rat. Drug Metab Dispos 1994; 22: 601-606.
7. Meisel S et al. Clinical pharmacokinetics of ramipril. Clin Pharmacokinet 1994; 26: 7-15.
8. Marguet D et al. Enhanced insulin secretion and improved glucose tolerance in mice lacking CD26. Proc Natl Acad Sci USA 2000; 97: 6874-6879.
9. Erickson RH et al. Biosynthesis and degradation of altered immature forms of intestinal dipeptidyl peptidase IV in a rat strain lacking the enzyme. J Biol Chem 1992; 267: 21623-21629.
10. Tsuji E et al. An active-site mutation (Gly633->Arg) of dipeptidyl peptidase IV causes its retention and rapid degradation in the endoplasmic reticulum. Biochemistry 1992; 31: 11921-11927.
11. Cheng HC et al. Is the Fischer 344/CRJ rat a protein-knock-out model for dipeptyl peptidase IV-medicated Lung metastasis of breast cancer? Clin Exp Metastasis 1999; 17: 609-615.
12. Gorrell MD et al. CD26: a multifunctional integral membrane and secreted protein of activated lymphocytes. Scand J Immunol 2001; 54: 249-264.
13. Watanabe Y et al. Deficiency of membrane-bound dipeptidyl aminopeptidase IV in a certain rat strain. Experientia 1987; 43: 400-401.
14. Cordero OJ et al. Preoperative serum CD26 levels: diagnostic efficiency and predictive value for colorectal cancer. Br J Cancer 2000; 83: 1139-1146.
15. Cuchacovich M et al. Characterization of human serum dipeptidyl peptidase IV (CD26) and analysis of its autoantibodies in patients with rheumatoid arthritis and other autoimmune diseases. Clin Exp Rheumatol 2001: 19: 673-680.
16. Thomas L et al. (R)-8-(3-aminopiperidin-1-yl)-7-but-2-ynyl-3- methyl-1-(4-methy1-quinazolin-2-ylmethyl)-3,7-dihydro-purine-2, 6-dione (BI 1356), a novel xanthine-based dipeptidyl peptidase 4 inhibitor, has a superior potency and longer duration of action compared with other DPP-4 inhibitors. J Pharmacol Exp Ther 2008:325: 175-182.
17. Rasmussen HB et al. Crystal structure of human dipeptidyl peptidase IV/CD26 in complex with a substrate analog. Nat Struct Biol 2003; 10: 19-25.
18. Chien CH et al. One site mutation disrupts dimer formation in human DPP-IV proteins. J Biol Chem 2004: 279: 52338-52345.
19. Longenecker KL et al. Crystal structures of DPP-IV (CD26) from rat kidney exhibit flexible accommodation of peptidase-selective inhibitors. Biochemistry 2006: 45: 7474-7482.
20. Hüttner S et al. Safety, tolerability. pharmacokinetics and pharmacodynamics of single oral doses of BI 1356. an inhibitor of dipeptidyl peptidase 4. in healthy male volunteers. J Clin Pharm 2008: 48: 1171-1178.