Comparison of serum phenytoin levels after administration with Dilantin Infatabs and Dilantin Kapseals via nasogastric tube feeding

Abstract

The purpose of this open-labelled, crossover clinical trial is to compare serum phenytoin levels after administration with Dilantin Infatabs (phenytoin acid tablet) and Dilantin Kapseals (phenytoin sodium capsule) through NG tube feeding. Patients enrolled were started with receiving Dilantin Infatabs 300 mg daily through NG tub feeding for at least 5 days the serum phyentoin level was determined. The dosage formulation was changed to Dilantin Kapseals 300 mg daily which was again administered through NG tube feeding for at least 5 days and serum phenytoin level was again determined. Seventeen subjects completed the whole process of study. Mean serum phenytoin concentrations after administration of phenytoin tablet and capsule were 6.03+-5.92 microgram/mL and 3.80+-2.71 microgram/mL, respectively. Mean serum albumin concentration measured at the time of phenytoin tablet and capsule administration were 2.51+-0.49 and 2.45+-0.40 g/dl, respectively. Mean serum phenytoin concentrations adjusted for their low serum albumin concentrations after administration of phenytoin tablet and capsule were 10.33+-11.60 and 6.28+-4.76 microgram/mL, respectively. Measured serum phenytoin concentrations and adjusted phenytoin concentrations after administration with phenytoin tablet and phenytoin capsule were significantly different (p=0.019 and p=0.035, respectively), The reasons which caused the serum phenytoin concentrations obtained from capsule to be significantly lower than that obtained from tablet was partly due to the sodium salt form of phenytoin in capsule while it is the free acid form in the tablet. During the study, all patients were seizure free and none of the patients showed serious adverse drug reaction. The mean Vmax/F (when assume Km=4 mg/L) after administration phenytoin tablet and phenytoin capsule were 501.32+-137.02 and 612.90+-346.18 mg/day, respectively. These values were not significantly different indicated that bioavailabilities of two dosage form were not significantly different. When the desired serum phenytoin concentration was set at 15 microgram/mL, the appropriate dosage required for phenytoin tablet and capsule were around 400 and 500 microgram/day. Since these predicted dosages were quite high and the bioavailability of either tablet or capsule was quite low and varied highly. Feeding standard dose of phenytoin (300 mg/day) 2 hours apart from feeding diet formula might be a safer method to increase serum phenytoin concentration. Further studies are strongly recommended before any definite conclusion could be made.