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.
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.


METHODS
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.


CONCLUSIONS
The effectiveness and safety of the regimen with rapid i.v. loading and the necessity to individualize phenytoin dosing after day 5 were demonstrated.
Martinelli
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EF
Department of Pharmacy, Kantonsspital, Aarau, Switzerland. enea.martinelli@spitalfmi.ch
Mühlebach
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SF
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000927:Anticonvulsants / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D001499:Bayes Theorem; D003201:Computers; D005260:Female; D006760:Hospitalization; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010672:Phenytoin / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics
D000927:Anticonvulsants; D010672:Phenytoin