Premium
Rapid i.v. loading with phenytoin with subsequent dose adaptation using non‐steady‐state serum levels and a Bayesian forecasting computer program to predict maintenance doses
Author(s) -
Martinelli E. F.,
Mühlebach S. F.
Publication year - 2003
Publication title -
journal of clinical pharmacy and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.622
H-Index - 73
eISSN - 1365-2710
pISSN - 0269-4727
DOI - 10.1046/j.0269-4727.2003.00506.x
Subject(s) - phenytoin , dosing , morning , confidence interval , medicine , evening , loading dose , regimen , maintenance dose , trough concentration , anesthesia , epilepsy , physics , astronomy , psychiatry
Summary Objective: To evaluate the suitability of a phenytoin loading dose regimen; to assess whether dose‐individualization was necessary and to investigate the reliability of a Bayesian forecasting method for phenytoin dose adaptation using non‐steady‐state levels in hospital‐admitted patients. Method: An initial loading dose (15 mg phenytoin acid/kg BW) was given i.v. over 4 h, followed by standardized maintenance doses given i.v. in 12‐h intervals from days 1 to 5 (175 mg ≤ 70 kg; 202 mg > 70 kg BW). The evening dose of day 5 was individualized based on three serum trough levels: L1 (after 16 h), L2 (morning day 4) and L3 (morning day 5). Results: Ninety of 136 consecutive patients were evaluable in a prospective study for the standardized phase; 50 of them had additional serum levels in the individualized phase. There was no exclusion of patients with interacting co‐medication. Seventy‐seven per cent (L1) and 68% (L3) of patients showed therapeutic values (10–20 mg/L). The prediction error of the forecasting was 3·95 mg/L, the root mean squared error 6·27 mg/L (target trough level 11 mg/L). Seventy per cent of the levels ( n =50) were within the 68% confidence interval. Conclusion: The effectiveness and safety of the regimen with rapid i.v. loading and the necessity to individualize phenytoin dosing after day 5 were demonstrated.