{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T16:38:57Z","timestamp":1724776737170},"reference-count":20,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,5,8]],"date-time":"2022-05-08T00:00:00Z","timestamp":1651968000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>To account for interindividual variability in the pharmacokinetics (PK) of factor concentrates, PK\u2010guided dosing is increasingly implemented in haemophilia patients. Calculations are based on provided label potency, but legislation allows a potency difference of \u00b120% between label and actual potency. It is unknown if these differences affect PK guidance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>Explore the effects of potency differences on individual factor VIII (FVIII) PK parameters and the prediction of FVIII trough levels of dosing regimens.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed individual preoperative PK profiling data from severe and moderate haemophilia A patients included in the OPTI\u2010CLOT randomized controlled trial. Label and actual potency were compared, with data on potency provided by pharmaceutical companies. For both potencies, individual PK parameters were estimated and concentration\u2010time curves were constructed by nonlinear mixed\u2010effects modelling. Finally, we explored the effect of both the identified and the maximum legislated potency difference on predicted FVIII trough levels infused in a low and high dose regimen.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In 45\/50 included patients, actual potency was higher than its label potency. The median potency difference was 6.0% (range \u20109.2% to 18.4%) and resulted in varying individual PK parameter estimates but practically identical FVIII concentration\u2010time curves. As expected, predicted FVIII trough levels were linearly correlated to the actual dose.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>It is not necessary to take potency differences into account when applying PK guidance of FVIII concentrates in haemophilia A patients. However, when the patient is switched to another FVIII batch after PK\u2010guided dosing, trough levels may deviate \u00b120% from calculations based on label dose.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.14575","type":"journal-article","created":{"date-parts":[[2022,5,8]],"date-time":"2022-05-08T10:43:31Z","timestamp":1652006611000},"page":"610-618","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Does difference between label and actual potency of factor VIII concentrate affect pharmacokinetic\u2010guided dosing of replacement therapy in haemophilia A?"],"prefix":"10.1111","volume":"28","author":[{"given":"Tine M.H.J.","family":"Goedhart","sequence":"first","affiliation":[{"name":"Department of Pediatric Hematology and Oncology Erasmus MC Sophia Children's Hospital University Medical Center Rotterdam  Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura H.","family":"Bukkems","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology \u2010 Hospital Pharmacy Amsterdam University Medical Centers  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iris","family":"van Moort","sequence":"additional","affiliation":[{"name":"Department of Hematology Erasmus MC University Medical Center Rotterdam  Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colin C.","family":"Spence","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology Erasmus MC Sophia Children's Hospital University Medical Center Rotterdam  Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel C.","family":"Zwaan","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology Erasmus MC Sophia Children's Hospital University Medical Center Rotterdam  Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moniek P.M.","family":"de Maat","sequence":"additional","affiliation":[{"name":"Department of Hematology Erasmus MC University Medical Center Rotterdam  Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ron A.A.","family":"Math\u00f4t","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology \u2010 Hospital Pharmacy Amsterdam University Medical Centers  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marjon H.","family":"Cnossen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology Erasmus MC Sophia Children's Hospital University Medical Center Rotterdam  Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"for the OPTI\u2010CLOT study group and SYMPHONY consortium","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,5,8]]},"reference":[{"key":"e_1_2_11_2_1","first-page":"1","volume-title":"Richtlijn Diagnostiek en behandeling van hemofilie en aanverwante hemostasestoornissen","author":"Leebeek 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