Animal pharmacokinetics of inogatran, a low-molecular-weight thrombin inhibitor with potential use as an antithrombotic drug

Biopharmaceutics and Drug Disposition

Volumn 19, Issue 1, 1998, Pages 55-64

  Eriksson, Ulf G ^a   Renberg, Lars ^a   Bredberg, Ulf ^a   Teger Nilsson, Ann Catrine ^a   Regardh, Carl Gunnar ^a  

^a ASTRAZENECA R AND D   (Sweden)

Author keywords

Animal pharmacokinetics; Inogatran; Thrombin inhibitor

Indexed keywords

INOGATRAN; THROMBIN INHIBITOR;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DOG; DOSE RESPONSE; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG EXCRETION; DRUG FECES LEVEL; DRUG HALF LIFE; DRUG METABOLISM; DRUG URINE LEVEL; HUMAN; HUMAN TISSUE; INTRAVENOUS DRUG ADMINISTRATION; ISOTOPE LABELING; MONKEY; NONHUMAN; NORMAL HUMAN; ORAL DRUG ADMINISTRATION; PLASMA; PLASMA PROTEIN BINDING; RAT;

ANIMALS; ANTITHROMBINS; AREA UNDER CURVE; BIOTRANSFORMATION; BLOOD PROTEINS; DOGS; FEMALE; GLYCINE; HALF-LIFE; HUMANS; MACACA FASCICULARIS; MALE; MOLECULAR WEIGHT; PIPERIDINES; RATS; RATS, SPRAGUE-DAWLEY; SPECIES SPECIFICITY;

EID: 0031908579     PISSN: 01422782     EISSN: None     Source Type: Journal    
DOI: 10.1002/(SICI)1099-081X(199801)19:1<55::AID-BDD74>3.0.CO;2-H     Document Type: Article

References (16)

1. A.-C. Teger-Nilsson, E. Gyzander, S. Andersson, M. Englund, C. Mattsson, J.-C. Ulvinge and D. Gustafsson, In vitro properties of inogatran, a new selective low molecular weight inhibitor of thrombin. Thromb. Haemostas, 73, 1325 (1995).
2. J.W. Fenton, H.A. Ofosu, D.G. Moon and J.M. Maraganore, Thrombin structure and function: why thrombin is the primary target for antithrombotics. Blood Coag. Fibrinol, 2, 69-75 (1991).
3. D. Gustafsson, M. Elg, S. Lenfors, I. Börjesson and A.-C. Teger-Nilsson, Effects of inogatran, a new low-molecular-weight thrombin inhibitor, in rat models of venous and arterial thrombosis, thrombolysis and bleeding time. Blood Coag. Fibrinol., 7, 69-79 (1996).
4. J. Hirsh, Heparin. New Engl. J. Med., 324, 1565-1574 (1991).
5. J. Hirsh, Low molecular weight heparin. Thromb. Haemostas., 70, 204-207 (1993).
6. J. Hirsh, Oral anticoagulants. New Engl. J. Med., 324, 1865-1875 (1991).
7. C. Tapparelli, R. Metternich, C. Ehrhardt and N.S. Cook, Synthetic low-molecular weight thrombin inhibitors: molecular design and pharmacological profile. Trends Pharmacol. Sci., 14, 366-376 (1993).
8. F. Markwardt: The development of hirudin as an antithrombotic drug. Thromb. Res., 74, 1-23 (1994).
9. L.R. Bush, Argatroban, a selective, potent thrombin inhibitor. Cardiovasc. Drug Rev., 9, 247-263 (1991).
10. K. Hilpert, I. Ackermann, D.W. Banner, A, Gast, K. Gubemator, P. Hadváry, L. Labler, K. Müller, G. Schmid, T.B. Tschopp and H. van de Waterbeemd, Design and synthesis of potent highly selective thrombin inhibitors. J. Med. Chem., 37, 3889-3901 (1994).
11. B. Davies and T, Morris, Physiological parameters in laboratory animals and humans. Pharm. Res., 10, 1093-1095 (1993).
12. J. Mordenti and W. Chappell, The use of interspecies scaling in toxicokinetics. In Toxicocokinetics and New Drug Development, A. Yacobi, J.P. Skelly and V.K. Batra (Eds), Pergamon, New York, 1989, pp. 42-97.
13. A.-C. Teger-Nilsson, U.G. Eriksson, D. Gustafsson, R. Bylund, G. Fager and P. Held, Phase I studies on inogatran, a new selective thrombin inhibitor. J. Am. Coll. Cardiol., 25, 117A (1995).
14. C.D. Klaassen and J.B. Watkins III, Mechanisms of bile formation, hepatic uptake, and biliary excretion. Pharmacol. Rev., 36, 1-67 (1984).
15. J. Hauptmann, B. Kaiser, M. Paintz, F. Markwardt, Biliary excretion of synthetic benzamidine-type thrombin inhibitors in rabbits and rats. Biomed. Biochim. Acta, 46, 445-453 (1987).
16. U. Echardt, W. Stüber, G. Dickneite, M. Reers, E. Petzinger, First pass elimination of a peptidomimetic thrombin inhibitor is due to carrier mediated uptake by the liver. Biochem. Pharmacol., 52, 85-96 (1996).