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Pharmacokinetics of Factor VIII in Humans

Obtaining Clinically Relevant Data from Comparative Studies

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Summary

The pharmacokinetics of Factor VIII procoagulant activity (FVIII:C) were investigated in 10 patients receiving 2 different high purity concentrates of FVIII. The in vivo recovery of FVIII:C depended on the method of blood volume estimation and on the in vitro assay used to define the potency of the concentrate; more generally, it also depends on the study design. The use of in vivo recovery to compare FVIII preparations should therefore be discouraged and the achieved area under the FVIII activity-time curve (AUC) should be used instead.

The volume of distribution at steady-state (Vss) of FVIII:C was significantly greater than the estimated plasma volume of the patients. The mean terminal half-life of FVIII:C was slightly assay-dependent, being 14h by a 1-stage clotting assay and 12h by a chromogenic assay. The calculated apparent clearance (CL) of FVIII:C, as well as the Vss and the in vivo recovery, depended on the measured in vitro potency of the FVIII concentrate.

These methodological aspects of pharmacokinetic studies are of direct interest to the clinician, since the routine administration of FVIII is based on the pharmacokinetic properties of the specific preparation.

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References

  • Allain J-P. Principles of in vivo recovery and survival studies. Scandinavian Journal of Haematology 33 (Suppl. 41): 123–130, 1984

    Google Scholar 

  • Allen TH, Peng MT, Chen KP, Huang TF, Chang C, et al. Prediction of blood volume and adiposity in man from body weight and cube of height. Metabolism 5: 328–345, 1956

    PubMed  CAS  Google Scholar 

  • Aronson DL. Factor VIII (antihaemophilic globulin). Seminars in Thrombosis and Hemostasis 6: 12–27, 1979

    Article  PubMed  CAS  Google Scholar 

  • Aronstam A, McLellan DS, Wassef M, Mbatha PS. Effect of height and weight on the in vivo recovery of transfused factor VIII C. Journal of Clinical Pathology 35: 289–291, 1982

    Article  PubMed  CAS  Google Scholar 

  • Barrowcliffe TW. Standardization of assays of factor VIII and factor IX. Research in Clinic and Laboratory 20: 155–165, 1990

    PubMed  CAS  Google Scholar 

  • Barrowcliffe TW, Edwards SJ, Kemball-Cook G, Thomas DP. Factor VIII degradation products in heated concentrates. Lancet 1: 1448–1449, 1986

    Article  PubMed  CAS  Google Scholar 

  • Boxenbaum HG, Riegelman S, Elashoff RM. Statistical estimations in pharmacokinetics. Journal of Pharmacokinetics and Biopharmaceutics 2: 123–148, 1974

    PubMed  CAS  Google Scholar 

  • Chiou WL. The phenomenon and rationale of marked dependence of drug concentration on blood sampling site: implications in pharmacokinetics, pharmacodynamics, toxicology and therapeutics (Parts I and II). Clinical Pharmacokinetics 17: 175–199, 1989

    Article  PubMed  CAS  Google Scholar 

  • Dawson NJ, Kemball-Cook G, Barrowcliffe TW. Assay discrepancies with highly purified factor VIII concentrates. Haemostasis 19: 131–137, 1989

    PubMed  CAS  Google Scholar 

  • Feldschuh J, Enson Y. Prediction of the normal blood volume: relation of blood volume to body habitus. Circulation 56: 605–612, 1977

    Article  PubMed  CAS  Google Scholar 

  • Gibaldi M, Perrier D. Pharmacokinetics. 2nd ed. Marcel Dekker, Inc, New York, 1982

    Google Scholar 

  • Harrison MH. Effects of thermal stress and exercise on blood volume in humans. Physiological Reviews 65: 149–209, 1985

    PubMed  CAS  Google Scholar 

  • Holford NHG, Sheiner LB. Understanding the dose-effect relationship: clinical application of pharmacokinetic-pharmacodynamic models. Clinical Pharmacokinetics 6: 429–453, 1981

    Article  PubMed  CAS  Google Scholar 

  • Kjellman H. Calculations of factor VIII in vivo recovery and half-life. Scandinavian Journal of Haematology 33 (Suppl. 40): 165–174, 1984

    Google Scholar 

  • Longo G, Matucci M, Messori A, Morfini M, Rossi-Ferrini PL. Pharmacokinetics of a new heat-treated concentrate of factor VIII estimated by model-independent methods. Thrombosis Research 42: 471–476, 1986

    Article  PubMed  CAS  Google Scholar 

  • Longo G, Matucci M, Morfini M, Vannini S, Messori A. A calculator program for individualizing factor VIII dosage. Drug Intelligence and Clinical Pharmacy 18: 726–730, 1984

    PubMed  CAS  Google Scholar 

  • Mannucci PM, Morfini M. Determination of pharmacokinetics of replacement factor VIII. Seminars in Hematology 27 (Suppl. 2): 8–10, 1990

    PubMed  CAS  Google Scholar 

  • Matucci M, Messori A, Donati-Cori G, Longo G, Vannini S, et al. Kinetic evaluation of four factor VIII concentrates by model-independent methods. Scandinavian Journal of Haematology 34: 22–28, 1985

    Article  PubMed  CAS  Google Scholar 

  • Mazurier C, Parquet-Gernez A, Goudemand M. Validation of a procedure for potency assessing of a high purity factor VIII concentrate — comparison of different factor VIII coagulant assays and effect of prediluent. Thrombosis and Haemostasis 64: 251–255, 1990

    PubMed  CAS  Google Scholar 

  • Messori A, Longo G, Matucci M, Morfini M, Rossi-Ferrini PL. Clinical pharmacokinetics of factor VIII in patients with classic haemophilia. Clinical Pharmacokinetics 13: 365–380, 1987

    Article  PubMed  CAS  Google Scholar 

  • Morfini M, Grasela TH, Longo G, Matucci M, Messori A, et al. Comparison of two pharmacokinetic techniques for individualizing factor VIII dosage in haemophilia patients. Haematologica 70: 454–456, 1985

    PubMed  CAS  Google Scholar 

  • Motulsky HJ, Ransnas LA. Fitting curves to data using nonlinear regression: a practical and nonmathematical review. FASEB Journal 1: 365–374, 1987

    PubMed  CAS  Google Scholar 

  • Nilsson IM. Haemorragic and thrombotic diseases, pp. 220–222, John Wiley & Sons, London, 1974

    Google Scholar 

  • Nilsson IM, Kirkwood TBL, Barrowcliffe TW. In vivo recovery of factor VIII: a comparison of one-stage and two-stage assay methods. Thrombosis and Haemostasis 42: 1230–1239, 1979

    PubMed  CAS  Google Scholar 

  • Over J, Sixma JJ, Doucet-De Bruine MHM, Trieschnigg AMC, Vlooswijk RAA, et al. Survival of 125iodine-labeled factor VIII in normals and patients with classic hemophilia. Journal of Clinical Investigation 62: 223–234, 1978

    Article  PubMed  CAS  Google Scholar 

  • Rosén S. Assay of factor VIII:C with a chromogenic substrate. Scandinavian Journal of Haematology 33 (Suppl. 40): 139–145, 1984

    Google Scholar 

  • Ruffo S, Messori A, Longo G, Matucci M, Morfini M, et al. A microcomputer program for individualizing factor VIII dosage in hemophilia patients undergoing major surgery. Computer Methods and Programs in Biomedicine 23: 37–46, 1986

    Article  PubMed  CAS  Google Scholar 

  • Rousell RH, Kasper CK, Schwartz RS. The pharmacology of a new pasteurized antihemophilic factor concentrate derived from human blood plasma. Transfusion 29: 208–212, 1989

    Article  PubMed  CAS  Google Scholar 

  • Schimpf K, Rothmann P, Schumacher K. Comparison of factor VIII concentrates in non-bleeding patients. Scandinavian Journal of Haematology 33 (Suppl. 41): 131–145, 1984

    Google Scholar 

  • Smith KJ, Lusher JM, Cohen AR, Salzman P. Initial clinical experience with a new pasteurized monoclonal antibody purified factor VIIIC. Seminars in Hematology 27 (Suppl. 2): 25–29, 1990

    PubMed  CAS  Google Scholar 

  • Sodetz JM, Pizzo SV, McKee PA. Relationship of sialic acid to function and in vivo survival of human factor VIII/von Willebrand factor protein. Journal of Biological Chemistry 252: 5538–5546, 1977

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Hospital Pharmacy, Department for Coagulation Disorders and Department of Community Health Sciences, Malmö General Hospital, Malmö, Sweden

    Sven Björkman, Maj Carlsson, Erik Berntorp & Pål Stenberg

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  1. Sven Björkman
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  2. Maj Carlsson
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  3. Erik Berntorp
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  4. Pål Stenberg
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Björkman, S., Carlsson, M., Berntorp, E. et al. Pharmacokinetics of Factor VIII in Humans. Clin. Pharmacokinet. 22, 385–395 (1992). https://doi.org/10.2165/00003088-199222050-00005

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