Intravenous phenytoin: a retrospective analysis of Bayesian forecasting versus conventional dosing in patients

In the hospital, medication management for effective antiepileptic therapy with phenytoin (PHT) often needs rapid IV loading and subsequent dose adjustment according to therapeutic drug monitoring (TDM).

To investigate PHT performance in reaching therapeutic target serum concentration rapidly and sustainably, a Bayesian forecasting (BF) regimen was compared to conventional dosing (CD), according to the official summary of product characteristics.

A 500-600 bed acute care teaching hospital in Switzerland, serving as a referral centre for neurology and neurosurgery.

In a retrospective, single centre, long-term analysis of hospitalized in- and out-patients, all PHT serum tests from the central hospital laboratory from 1997 to 2007 were assessed. The BF regimen consisted of a guided, body weight-adapted rapid IV PHT loading over 5 days with pre-defined TDM time points. The conventional dosage was performed without written guidance. Assuming non-normally distributed data, non-parametric statistical methods for analysis were applied.

The extent of target therapeutic PHT serum levels (40-80 μmol/L) was measured and compared between the two regimens. Also, the influence of gender and age was analysed.

A total of 6,120 PHT serum levels (2,819 BF and 3,301 conventionally dosed) from 2,589 patients (869 BF and 1,720 conventionally dosed) were evaluated and compared. 63.6 % of the PHT serum levels from the BF group were within the therapeutic range, compared with only 34.0 % in the conventional group (p < 0.0001). The mean BF serum level was 52.0 ± 22.1 μmol/L (within target range) (n = 2,819), whereas the mean serum level of the CD was 39.8 ± 28.2 μmol/L (sub-target range) (n = 3,301). In the BF group, men had small but significantly lower PHT serum levels compared to women (p < 0.0001). The conventionally dosed group showed no significant gender differences (p = 0.187). A comparative sub-analysis of age-related groups (children, adolescents, adults, seniors, and elderly) showed significantly lower target levels (p < 0.0001) for each group in the conventional dosed group, compared to BF.

Comparing the two cohorts, BF with the well-defined dose regimen showed significantly better performance in reaching therapeutic PHT serum levels rapidly and for longer duration.