Pharmacokinetics and pharmacodynamics of recombinant factor VIIa
1994; Wiley; Volume: 55; Issue: 6 Linguagem: Inglês
10.1038/clpt.1994.80
ISSN1532-6535
AutoresCeleste Lindley, William T. Sawyer, B. Gail Macik, Jean Lusher, Justin F Harrison, Kelly Baird-Cox, Kel Birch, Stephen Glazer, Harold R. Roberts,
Tópico(s)Platelet Disorders and Treatments
ResumoClinical Pharmacology & TherapeuticsVolume 55, Issue 6 p. 638-648 Pharmacokinetics and Drug Disposition Pharmacokinetics and pharmacodynamics of recombinant factor VIIa Celeste M Lindley PharmD, Corresponding Author Celeste M Lindley PharmD University of North Carolina and Center for Thrombosis and Hemostasis, Chapel Hill Duke University Medical Center, Durham Children's Hospital, Detroit University Hospital of Wales, Cardiff Novo Nordisk, GentofteSchool of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7360.Search for more papers by this authorWilliam T Sawyer MS, William T Sawyer MS University of North Carolina and Center for Thrombosis and Hemostasis, Chapel Hill Duke University Medical Center, Durham Children's Hospital, Detroit University Hospital of Wales, Cardiff Novo Nordisk, GentofteSearch for more papers by this authorB Gail Macik MD, B Gail Macik MD University of North Carolina and Center for Thrombosis and Hemostasis, Chapel Hill Duke University Medical Center, Durham Children's Hospital, Detroit University Hospital of Wales, Cardiff Novo Nordisk, GentofteSearch for more papers by this authorJean Lusher MD, Jean Lusher MD University of North Carolina and Center for Thrombosis and Hemostasis, Chapel Hill Duke University Medical Center, Durham Children's Hospital, Detroit University Hospital of Wales, Cardiff Novo Nordisk, GentofteSearch for more papers by this authorJustin F Harrison MD, Justin F Harrison MD University of North Carolina and Center for Thrombosis and Hemostasis, Chapel Hill Duke University Medical Center, Durham Children's Hospital, Detroit University Hospital of Wales, Cardiff Novo Nordisk, GentofteSearch for more papers by this authorKelly Baird-Cox BS, Kelly Baird-Cox BS University of North Carolina and Center for Thrombosis and Hemostasis, Chapel Hill Duke University Medical Center, Durham Children's Hospital, Detroit University Hospital of Wales, Cardiff Novo Nordisk, GentofteSearch for more papers by this authorKel Birch MD, Kel Birch MD University of North Carolina and Center for Thrombosis and Hemostasis, Chapel Hill Duke University Medical Center, Durham Children's Hospital, Detroit University Hospital of Wales, Cardiff Novo Nordisk, GentofteSearch for more papers by this authorStephen Glazer MD, Stephen Glazer MD University of North Carolina and Center for Thrombosis and Hemostasis, Chapel Hill Duke University Medical Center, Durham Children's Hospital, Detroit University Hospital of Wales, Cardiff Novo Nordisk, GentofteSearch for more papers by this authorHarold R Roberts MD, Harold R Roberts MD University of North Carolina and Center for Thrombosis and Hemostasis, Chapel Hill Duke University Medical Center, Durham Children's Hospital, Detroit University Hospital of Wales, Cardiff Novo Nordisk, GentofteSearch for more papers by this author Celeste M Lindley PharmD, Corresponding Author Celeste M Lindley PharmD University of North Carolina and Center for Thrombosis and Hemostasis, Chapel Hill Duke University Medical Center, Durham Children's Hospital, Detroit University Hospital of Wales, Cardiff Novo Nordisk, GentofteSchool of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7360.Search for more papers by this authorWilliam T Sawyer MS, William T Sawyer MS University of North Carolina and Center for Thrombosis and Hemostasis, Chapel Hill Duke University Medical Center, Durham Children's Hospital, Detroit University Hospital of Wales, Cardiff Novo Nordisk, GentofteSearch for more papers by this authorB Gail Macik MD, B Gail Macik MD University of North Carolina and Center for Thrombosis and Hemostasis, Chapel Hill Duke University Medical Center, Durham Children's Hospital, Detroit University Hospital of Wales, Cardiff Novo Nordisk, GentofteSearch for more papers by this authorJean Lusher MD, Jean Lusher MD University of North Carolina and Center for Thrombosis and Hemostasis, Chapel Hill Duke University Medical Center, Durham Children's Hospital, Detroit University Hospital of Wales, Cardiff Novo Nordisk, GentofteSearch for more papers by this authorJustin F Harrison MD, Justin F Harrison MD University of North Carolina and Center for Thrombosis and Hemostasis, Chapel Hill Duke University Medical Center, Durham Children's Hospital, Detroit University Hospital of Wales, Cardiff Novo Nordisk, GentofteSearch for more papers by this authorKelly Baird-Cox BS, Kelly Baird-Cox BS University of North Carolina and Center for Thrombosis and Hemostasis, Chapel Hill Duke University Medical Center, Durham Children's Hospital, Detroit University Hospital of Wales, Cardiff Novo Nordisk, GentofteSearch for more papers by this authorKel Birch MD, Kel Birch MD University of North Carolina and Center for Thrombosis and Hemostasis, Chapel Hill Duke University Medical Center, Durham Children's Hospital, Detroit University Hospital of Wales, Cardiff Novo Nordisk, GentofteSearch for more papers by this authorStephen Glazer MD, Stephen Glazer MD University of North Carolina and Center for Thrombosis and Hemostasis, Chapel Hill Duke University Medical Center, Durham Children's Hospital, Detroit University Hospital of Wales, Cardiff Novo Nordisk, GentofteSearch for more papers by this authorHarold R Roberts MD, Harold R Roberts MD University of North Carolina and Center for Thrombosis and Hemostasis, Chapel Hill Duke University Medical Center, Durham Children's Hospital, Detroit University Hospital of Wales, Cardiff Novo Nordisk, GentofteSearch for more papers by this author First published: June 1994 https://doi.org/10.1038/clpt.1994.80Citations: 81 Presented in part at the Fourteenth Annual Meeting of the American College of Clinical Pharmacy, Reno, Nevada, August 18, 1993. AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract Objective To evaluate the pharmacokinetics and pharmacodynamics of recombinant activated factor VII (rFVIIa). Methods Single-dose pharmacokinetics of three dose levels (17.5, 35, and 70 µg/kg) of rFVIIa were investigated in 15 patients with hemophilia with severe factor VIII or factor IX deficiency (with or without inhibitors) while they were in the nonbleeding state and during bleeding episodes. Factor VII clotting activity (FVII:C) was determined 5 minutes before and at 10, 20, and 50 minutes and 2, 4, 6, 8, 12, and 24 hours after rFVIIa administration. Model-independent pharmacokinetic analysis of FVII:C plasma concentration—time data included determination of plasma clearance, mean residence time, and volume of distribution. rFVIIa recovery was determined from the plasma FVII:C observed 10 minutes after administration. Pharmacodynamic assessments of prothrombin time, activated partial thrombo-plastic time, and Factor X values obtained concurrently with FVII: C samples were performed. Results Sufficient data to allow pharmacokinetic parameter calculation were available for 25 nonbleeding episodes in 11 patients (17.5 µg/kg, n = 8; 35 µg/kg, n = 9; 70 µg/kg, n = 8) and for five bleeding episodes in three patients (17.5 µg/kg, n = 2; 35 (µg/kg, n = 2; 35 µg/kg, n = 1). Recovery was calculated during 27 nonbleeding and 17 bleeding episodes. rFVIIa distribution volume is two to three times that of plasma. Median clearance was low—31.0 ml/hr · kg in nonbleeding episodes and 32.5 mg/hr · kg in bleeding episodes. In nonbleeding episodes, median mean residence time was 3.44 hours and median half-life was 2.89 hours. In bleeding episodes, the elimination rate appears to be higher, with a median mean residence time of 2.97 hours and a median half-life of 2.30 hours. Recovery was 45.6% during nonbleeding conditions and 43.5% during bleeding episodes (p = 0.0006); it was statistically lower with the highest dose level than with the 17.5 and 35 µ/kg doses (p = 0.007). A significant statistical relationship was observed between values of the prothrombin time and activated partial thromboplastin time, and values of FVII:C with use of maximum effect model. Conclusions The pharmacokinetics of rFVIIa are linear in the dose range evaluated. The results suggest potential value of prothrombin time determination in the monitoring of rFVIIa therapy. Clinical Pharmacology and Therapeutics (1994) 55, 638–648; doi:10.1038/clpt.1994.80 Citing Literature Volume55, Issue6June 1994Pages 638-648 RelatedInformation
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