VIGABATRIN-INDUCED DECREASE IN SERUM PHENYTOIN CONCENTRATION DOES NOTINVOLVE A CHANGE IN PHENYTOIN BIOAVAILABILITY

The possibility that vigabatrin (VGB) decreases serum phenytoin (PHT) concentration by lowering the oral bioavailability of PHT was investig ated in 21 patients with epilepsy. Each patient was switched from oral to intravenous PHT for 5 days before and after combined treatment wit h VGB. After VGB (2-3.5 g day-1 for at least 5 weeks), serum PHT conce ntrations decreased slightly from 87 +/- 25 to 76 +/- 31 mumol l-1 (me ans +/- s.d., P < 0.05), but in a subgroup of seven patients the decre ase was more prominent (from 72 +/- 22 to 49 +/- 17 mumol l-1, P < 0.0 05). At baseline (before VGB), serum PHT remained unaffected (85 +/- 3 0 mumol l-1) after switching PHT dosage to the intravenous route, indi cating that the oral availability of the drug was virtually complete. During VGB treatment, serum PHT was also unchanged (74 +/- 34 mumol l- 1) after switching from oral to intravenous therapy, and this was also true for the subgroup of patients showing a prominent interaction (48 +/- 18 mumol l-1). The urinary recoveries of PHT and its metabolites pHPPH and mHPPH remained constant throughout the study. It is conclude d that the oral availability of PHT is unaffected by VGB and that the VBG-induced decrease in serum PHT is mediated by alternative mechanism s.