Pharmacokinetics of two pasteurized Factor VIII concentrates by different and multicenter assays of Factor VIII activity

Messori, Andrea; Morfini, Massimo; Blombäck, Margareta; Cinotti, S.; Longo, Giovanni; Schimpf, Kl.; Schumacher, Katja; Novakova-Banet, A.; Delvos, U.; Kjellman, H

doi:10.1016/0049-3848(92)90109-n

Cited by 14 publications

(20 citation statements)

References 7 publications

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“…A summary of IVR from crossover studies of FVIII [17][18][19][20] and FIX [21][22][23] PK is reported in Table 1.…”

Section: Resultsmentioning

confidence: 99%

“…Very wide standard deviations (SD) have been observed in all studies, in particularly in the Recombinate study, due to an extremely large range of results (1.43-3.337 dL kg )1 ). The data from five FVIII PK studies [7,[17][18][19][20] have been analysed according to the procedure described in point 2 above, and the results are reported in [7,[17][18][19][20]24] are reported in Table 3-6 for FVIII and in Table 7 for FIX. The FVIII concentration has been accordingly increased by 18%)20%.…”

Section: Resultsmentioning

confidence: 99%

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Pharmacokinetics of factor VIII and factor IX

Morfini

2003

Haemophilia

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A survey of principal pharmacokinetic (PK) studies on factor VIII (FVIII) and factor IX (FIX) plasma- and rDNA-derived concentrates, analysed by means of the PKRD program, has been performed. Notwithstanding the accurate definition of the study design, released in 1991 by the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis (SSC-ISTH), a large variability of PK parameters has been pointed out. In the majority of the PK studies, the size of the population is small. In this situation, a careful individualization of haemophilia therapy is strongly recommended. The tailored prediction of loading and maintenance dosages and the need for strict control of trough FVIII/IX levels are mandatory not only to decrease the risk of bleeds but also to spare financial resources. Recently, the old problem of FVIII assay standardization has again become a concern among physicians, especially after the introduction of B-domain deleted rFVIII concentrate. The discrepancies between the widely used one-stage clotting assay and the chromogenic substrate assay seem to be solved by the introduction of a product-specific laboratory standard.

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“…A summary of IVR from crossover studies of FVIII [17][18][19][20] and FIX [21][22][23] PK is reported in Table 1.…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Pharmacokinetics of factor VIII and factor IX

Morfini

2003

Haemophilia

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“…The pharmacokinetic results achieved are usually considered equivalent or comparable if the pharmacokinetic approach is similar. In the case of FVIII, a plasma protein, differences have been described in pharmacokinetic parameters depending on the commercial preparation [4]. It could be explained because a biological product is subjected to different purification/preparation methods.…”

Section: Discussionmentioning

confidence: 99%

“…The patients' age ranged from 15 to 43 years (median 23 years) and their body weight ranged from 45 to 82 kg (median 58 kg). The inclusion/exclusion criteria were similar to those described previously [4]. Each patient was administered a single dose of 30-50 IU kg )1 body weight (the closest multiple of whole vials) of monoclonal purified FVIII (Monoclate-P, Armour Pharm.…”

Section: Methodsmentioning

confidence: 99%

Comparative study of four different pharmacokinetic computer programs: case study of a factor VIII preparation

Planas-Pascual

Montoro

1997

European Journal of Clinical Pharmacology

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Pharmacokinetic parameters differed depending on the computer program used to analyse the same data set. The same patient data used in different computer programs will result in significantly different parameter estimations, although the non-compartmental approach is less affected by variation, and this should be taken into consideration for comparative purposes, for the development of new preparations and for the implications in patient care and therapy monitoring.

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“…A European multicentre study aimed to assess the reproducibility of one- and two-stage clotting methods and chromogenic assay of FVIII showed a good agreement between one-stage clotting and chromogenic assay in a wide range of concentrations, while two-stage clotting assay was not well reproducible [40]. The same PK study design was employed for another multicentre study comparing two pasteurised clotting factor concentrates, Haemate P vs. FVIII CS from CSL Behring [41]. Similar discrepancies between one-stage clotting and chromogenic assay resulted some years later [42] in a multicentre PK study of the new B-domain deleted FVIII concentrate, moroctocog alfa.…”

Section: Dna-recombinant Clotting Factor Concentrates and Their Phmentioning

confidence: 99%

The History of Clotting Factor Concentrates Pharmacokinetics

Morfini¹

2017

JCM

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Clotting factor concentrates (CFCs) underwent tremendous modifications during the last forty years. Plasma-derived concentrates made the replacement therapy feasible not only in the hospital but also at patients’ home by on-demand or prophylactic regimen. Virucidal methods, implemented soon after hepatitis and AIDS outbreak, and purification by Mabs made the plasma-derived concentrates safer and purer. CFCs were considered equivalent to the other drugs and general rules and methods of pharmacokinetics (PK) were applied to their study. After the first attempts by graphical methods and calculation of In Vivo Recovery, compartment and non-compartment methods were applied also to the study of PK of CFCs. The bioequivalence of the new concentrates produced by means of recombinant DNA biotechnology was evaluated in head-to-head PK studies. Since the beginning, the large inter-patient variability of dose/response of replacement therapy was realized. PK allowed tailoring haemophilia therapy and PK driven prophylaxis resulted more cost effective. Unfortunately, the need of several blood samples and logistic difficulties made the PK studies very demanding. Recently, population PK (PopPK) has been applied to the prediction of CFCs dosing by Bayesian methodology. By PopPK also sparse data may allow evaluating the appropriateness of replacement therapy.

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Pharmacokinetics of two pasteurized Factor VIII concentrates by different and multicenter assays of Factor VIII activity

Cited by 14 publications

References 7 publications

Pharmacokinetics of factor VIII and factor IX

Pharmacokinetics of factor VIII and factor IX

Comparative study of four different pharmacokinetic computer programs: case study of a factor VIII preparation

The History of Clotting Factor Concentrates Pharmacokinetics

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