Proposal for individualized dosing of eculizumab in atypical haemolytic uraemic syndrome: patient friendly and cost-effective
| Autor: | Avest, M. ter, Bouwmeester, R.N., Duineveld, C., Wijnsma, K.L., Volokhina, E.B., Heuvel, L.P.W.J. van den, Burger, D.M., Wetzels, J.F.M., Adang, E.M.M., Kar, N.C.A.J. van de, Heine, R. ter |
|---|---|
| Rok vydání: | 2023 |
| Předmět: |
All institutes and research themes of the Radboud University Medical Center
Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11] lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4] Renal disorders Radboud Institute for Health Sciences [Radboudumc 11] Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18] |
| Zdroj: | Nephrology, Dialysis, Transplantation, 38, 362-371 Nephrology, Dialysis, Transplantation, 38, 2, pp. 362-371 |
| ISSN: | 0931-0509 |
| Popis: | Contains fulltext : 291080.pdf (Publisher’s version ) (Open Access) BACKGROUND: Eculizumab is a lifesaving yet expensive drug for atypical haemolytic uraemic syndrome (aHUS). Current guidelines advise a fixed-dosing schedule, which can be suboptimal and inflexible in the individual patient. METHODS: We evaluated the pharmacokinetics (PK) and pharmacodynamics (PD) [classical pathway (CP) activity levels] of eculizumab in 48 patients, consisting of 849 time-concentration data and 569 CP activity levels. PK-PD modelling was performed with non-linear mixed-effects modelling. The final model was used to develop improved dosing strategies. RESULTS: A PK model with parallel linear and non-linear elimination rates best described the data with the parameter estimates clearance 0.163 L/day, volume of distribution 6.42 L, maximal rate 29.6 mg/day and concentration for 50% of maximum rate 37.9 mg/L. The PK-PD relation between eculizumab concentration and CP activity was described using an inhibitory Emax model with the parameter estimates baseline 101%, maximal inhibitory effect 95.9%, concentration for 50% inhibition 22.0 mg/L and Hill coefficient 5.42. A weight-based loading dose, followed by PK-guided dosing was found to improve treatment. On day 7, we predict 99.95% of the patients to reach the efficacy target (CP activity |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|