The dipeptidyl peptidase-4 inhibitor linagliptin exhibits time- and dose-dependent localization in kidney, liver, and intestine after intravenous dosing: Results from high resolution autoradiography in rats

Drug Metabolism and Disposition

Volumn 38, Issue 9, 2010, Pages 1443-1448

  Greischel, Andreas ^a   Binder, Rudolf ^a   Baierl, Juergen ^a  

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

Author keywords

[No Author keywords available]

Indexed keywords

DIPEPTIDYL PEPTIDASE IV INHIBITOR; LINAGLIPTIN; TRITIUM; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; AUTORADIOGRAPHY; BILE DUCT; BRUSH BORDER; CELLULAR DISTRIBUTION; CONTROLLED STUDY; DOSE RESPONSE; DOSE TIME EFFECT RELATION; DRUG BINDING; DRUG DISTRIBUTION; DRUG DOSE INCREASE; DRUG MEGADOSE; GLOMERULUS; HENLE LOOP; INTESTINE VILLUS; KIDNEY; KIDNEY COLLECTING TUBULE; KIDNEY DISTAL TUBULE; KIDNEY PROXIMAL TUBULE; LAMINA PROPRIA; LIVER; LOW DRUG DOSE; MALE; NONHUMAN; PRIORITY JOURNAL; RADIOACTIVITY; RAT; SMALL INTESTINE;

ANIMALS; DIPEPTIDYL-PEPTIDASE IV INHIBITORS; INFUSIONS, INTRAVENOUS; INTESTINES; KIDNEY; LIVER; MALE; PURINES; QUINAZOLINES; RATS; TISSUE DISTRIBUTION;

RATTUS;

EID: 77956007404     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.110.034199     Document Type: Article

References (16)

1. Deacon CF and Holst JJ (2010) Linagliptin, a xanthine-based dipeptidyl peptidase-4 inhibitor with an unusual profile for the treatment of type 2 diabetes. Expert Opin Investig Drugs 19:133-140.
2. Eckhardt M, Hauel N, Himmelsbach F, Langkopf E, Nar H, Mark M, Tadayyon M, Thomas L, Guth B, and Lotz R (2008) 3,5-Dihydro-imidazol[4,5 days]pyridazin-4-ones: a class of potent DPP-4 inhibitors. Bioorg Med Chem Lett 18:3158-3162. (Pubitemid 351718346)
3. Fuchs H, Binder R, and Greischel A (2009a) Tissue distribution of the novel DPP-4 inhibitor BI 1356 is dominated by saturable binding to its target in rats. Biopharm Drug Dispos 30:229-240.
4. Fuchs H, Tillement JP, Urien S, Greischel A, and Roth W (2009b) 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. J Pharm Pharmacol 61:55-62.
5. Fukasawa KM, Fukasawa K, Sahara N, Harada M, Kondo Y, and Nagatsu I (1981) Immunohistochemical localization of dipeptidyl aminopeptidase IV in rat kidney, liver, and salivary glands. J Histochem Cytochem 29:337-343. (Pubitemid 11145976)
6. Hansen L, Deacon CF, Orskov C, and Holst JJ (1999) Glucagon-like peptide-1-(7-36)amide is transformed to glucagon-like peptide-1-(9 -36)amide by dipeptidyl peptidase IV in the capillaries supplying the L cells of porcine intestine. Endocrinology 140:5356-5363.
7. Hartel S, Gossrau R, Hanski C, and Reutter W (1988a) Dipeptidyl peptidase (DPP) IV in rat organs. Comparison of immunohistochemistry and activity histochemistry. Histochemistry 89:151-161.
8. Hartel S, Hanski C, Neumeier R, Gossrau R, and Reutter W (1988b) Characterization of different forms of dipeptidyl peptidase IV from rat liver and hepatoma by monoclonal antibodies. Adv Exp Med Biol 240:207-214.
9. Hartel-Schenk S, Gossrau R, and Reutter W (1990) Comparative immunohistochemistry and histochemistry of dipeptidyl peptidase IV in rat organs during development. Histochem J 22:567-578.
10. Heise T, Graefe-Mody EU, Hüttner S, Ring A, Trommeshauser D, and Dugi KA (2009) Pharmacokinetics, pharmacodynamics and tolerability of multiple oral doses of linagliptin, a dipeptidyl peptidase-4 inhibitor in male type 2 diabetes patients. Diabetes Obes Metab 11:786-794.
11. Hong WJ, Petell JK, Swank D, Sanford J, Hixson DC, and Doyle D (1989) Expression of dipeptidyl peptidase IV in rat tissues is mainly regulated at the mRNA levels. Exp Cell Res 182:256-266. (Pubitemid 19123471)
12. Kettmann U, Humbel B, and Holzhausen HJ (1992) Ultrastructural localization of dipeptidylpeptidase IV in the glomerulum of the rat kidney. Acta Histochem 92:225-227.
13. Lambeir AM, Durinx C, Scharpé S, and De Meester I (2003) Dipeptidyl-peptidase IV from bench to bedside: an update on structural properties, functions, and clinical aspects of the enzyme DPP IV. Crit Rev Clin Lab Sci 40:209-294.
14. Mentlein R (1999) Dipeptidyl-peptidase IV (CD26) - role in the inactivation of regulatory peptides. Regul Pept 85:9-24.
15. Retlich S, Withopf B, Greischel A, Staab A, Jaehde U, and Fuchs H (2009) Binding to dipeptidyl peptidase-4 determines the disposition of linagliptin (BI 1356) - investigations in DPP-4 deficient and wildtype rats. Biopharm Drug Dispos 30:422-436.
16. Stumpf WE (2003) Drug localization in tissues and cells. Receptor microscopic autoradiography. A basis for tissue and cellular pharmacokinetics, drug targeting, delivery and prediction, in International Institute of Drug Distribution, Cytopharmacology and Cytotoxicology, IDDC Press, Chapel Hill, NC.