Integrated pharmacokinetic/pharmacodynamic model of XV459, a potent and specific GPIIb/IIIa inhibitor, in healthy male volunteers

Journal of Clinical Pharmacology

Volumn 42, Issue 12, 2002, Pages 1326-1334

  Fossler, Michael J ^a,h   Ebling, William F ^a,e   Ma, Su ^a,f   Kornhauser, David ^a,g   Mondick, John ^a   Barrett, Jeffrey S ^a,d   Garner, Dennis ^a   Quon, Check Y ^a,c   Pieniaszek Jr , Henry J ^a,b  

^a DUPONT COMPANY   (United States)

^b HPP Consulting and Services Inc   (United States)

^c iNDA Consulting   (United States)

^d SANOFI   (France)

^e PHARSIGHT CORPORATION   (United States)

^f MERCK RESEARCH LABORATORIES   (United States)

^g BRISTOL MYERS SQUIBB   (United States)

^h GLAXOSMITHKLINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3 [[[3 [4 (AMINOIMINOMETHYL)PHENYL] 4,5 DIHYDRO 5 ISOXAZOLYL]ACETYL]AMINO] N (BUTOXYCARBONYL)ALANINE; ADENOSINE DIPHOSPHATE; FIBRINOGEN RECEPTOR ANTAGONIST; PRODRUG; ROXIFIBAN;

ADULT; AGE; AGED; ARTICLE; BODY WEIGHT; CLINICAL TRIAL; COMPARTMENT MODEL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DISTRIBUTION; HUMAN; LIQUID CHROMATOGRAPHY; MALE; MASS SPECTROMETRY; MULTIPLE DRUG DOSE; NORMAL HUMAN; RANDOMIZED CONTROLLED TRIAL; STATISTICAL MODEL; THROMBOCYTE AGGREGATION; THROMBOCYTE AGGREGATION INHIBITION; THROMBOCYTE COUNT;

ADMINISTRATION, ORAL; AGED; AMIDINES; AMINO ACIDS; AREA UNDER CURVE; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; HALF-LIFE; HUMANS; ISOXAZOLES; MIDDLE AGED; MODELS, BIOLOGICAL; PLATELET GLYCOPROTEIN GPIIB-IIIA COMPLEX; PRODRUGS;

EID: 0036891165     PISSN: 00912700     EISSN: None     Source Type: Journal    
DOI: 10.1177/0091270002042012003     Document Type: Article

References (23)

1. 3 binding sites in the guinea pig. Biopharm Drug Dispos 1999;20:309-318.
2. Mousa SA, Kapil R, Mu DX: Intravenous and oral antithrombotic efficacy of the novel platelet GPIIb/IIIa antagonist roxifiban (DMP754) and its free acid form, XV459. Arterioscler Thromb Vasc Biol 1999;19:2535-2541.
3. Mousa SA, Bozarth JM, Lorelli W, Forsythe MS, et al: Antiplatelet efficacy of XV459, a novel nonpeptide platelet GPIIb/IIIa antagonist: Comparative platelet binding profiles with c7E3. Pharmacol Exp Ther 1998;286:1277-1284.
4. Daly R, Ebling W, Pieniaszek H, Cain V, Kopecky S, Murphy J: Roxifiban, a new oral IIb/IIIa glycoprotein receptor antagonist, in patients with coronary artery disease. Paper presented at the Lancet Conference, "The Challenge of Acute Coronary Syndromes," Copenhagen, Denmark, June 10-11, 1999.
5. Kapil RP, Padovani PK, Garner DM, Chien BM, Quon CY, Lam GN: Nonlinear pharmacokinetics of a novel platelet glycoprotein IIb/IIIa receptor antagonist, XV459, in beagle dogs. Pharm Res 1996;13(9, suppl.):S-497.
6. Hardman JG, Limbird LE, Molinoff PB, Ruddon RW, Gilman AG (eds.): Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th ed. New York: McGraw-Hill, 1996.
7. Pieniaszek HJ, Sy S, Ebling WF, Fossler MJ, Cain V, Mondick JT, et al: DM safety, tolerability, pharmacokinetics, and time-course of pharmacologic response of the active moiety of roxifiban, XV459, a potent GP IIb/IIIa antagonist, following oral administration in healthy volunteers. J Clin Pharmacol 2002;42:738-753.
8. Aungst BJ, personal communication, May 2, 2000.
9. Ebling WF, Kornhauser DM, Ma S, Oliver JS, Pieniaszek HJ: The influence of food and fasting duration on the pharmacokinetics and pharmacodynamics of roxifiban, a glycoprotein IIb/IIIa antagonist. J Clin Pharmacol 1999;39(9):983.
10. Food and Drug Administration: Guidance for Industry: Population Pharmacokinetics, February 1999 [Online]. Available: www.fda.gov/cder/guidance/index.htm
11. Coller BS: Monitoring platelet GPIIb/IIIa antagonist therapy. Blood Coag Fibrinolysis 1999;10(suppl. 1):S81-S86.
12. Barrett JS, Murphy G, Peerlinck K, De Lepeleire I, et al: Pharmacokinetics and pharmacodynamics of MK-383, a selective non-peptide platelet glycoprotein-IIb/IIIa receptor antagonist, in healthy men. Clin Pharmacol Ther 1994;56:377-388.
13. Kleiman NS: Pharmacokinetics and pharmacodynamics of glycoprotein GPIIb/IIIa inhibitors. Am Heart J 1999;138:S263-275.
14. EPIC Investigators: Use of a monoclonal antibody directed against the platelet glycoprotein GPIIb/IIIa receptor in high-risk coronary angioplasty. N Engl J Med 1994;330:956-961.
15. IMPACT-II Investigators: Randomized placebo-controlled trial of the effect of eptifibatide on complications of percutaneous coronary intervention: The IMPACT-II trial. Lancet 1997;348:1422-1428.
16. Cannon CP, McCabe CH, Wilcox RG, Langer A, et al: Oral glycoprotein GPIIb/IIIa inhibition with orbofiban in patients with unstable coronary syndromes (OPUS-TIMI 16 trial). Circulation 2000;102(2):149-156.
17. Cannon CP, McCabe CH, Borzak S, Henry TD, et al: Randomized trial of an oral glycoprotein GPIIb/IIIa antagonist, sibrafiban, in patients after an acute coronary syndrome: Results of the TIMI 12 trial. Circulation 1998;97(4):340-349.
18. O'Neill WW, Serruys P, Knudtson M, van Es GA, et al: Long-term treatment with a platelet glycoprotein-receptor antagonist after percutaneous coronary revascularization. EXCITE Trial Investigators. Evaluation of oral Xemilofiban in controlling thrombotic events. N Engl J Med 2000;342(18):1316-1324.
19. SYMPHONY Investigators: Comparison of sibrafiban with aspirin for prevention of cardiovascular events after acute coronary syndromes: A randomized trial. Lancet 2000;355:337-345.
20. Heeschen C, Hamm CW: Commentary: Difficulties with oral platelet glycoprotein GPIIb/IIIa receptor antagonists. Lancet 2000;355:330-331.
21. Kereiakes DJ: Oral blockade of the platelet glycoprotein GPIIb/IIIa receptor: Fact or fancy? Am Heart J 1999;138:S39-S46.
22. Theroux P: Oral inhibitors of platelet membrane receptor glycoprotein GPIIb/IIIa in clinical cardiology: issues and opportunities. Am Heart J 1998;135(5, Pt. 2):S107-S112.
23. Modi NB, Novotny W, Reimann JD, Cannon CP, et al: Pharmacokinetics and pharmacodynamics of sibrafiban, an orally administered GPIIb/IIIa antagonist, in patients with acute coronary syndrome. J Clin Pharmacol 1999;39:675-684.