Phenytoin bioavailability assessed by steady state serum concentrations.
The effect of a change in bioavailability of phenytoin sodium formulations on steady state serum concentrations was assessed in two groups of neurosurgical patients (n = 20 and 12). One group was studied in 1980 while on the old formulation, the other in 1983 while on the new formulation. Data were also obtained from routine therapeutic-level monitorings in 85 ambulatory patients receiving the new formulation during 1984. Phenytoin levels on the 400-mg/day dose were 10.9 +/- 4.1 (SD) and 16.1 +/- 5.6 micrograms/ml on the old and new formulations, respectively (P less than 0.01) in the neurosurgical patients. Routinely monitored levels on the 300-mg/day dose were 6.9 +/- 4.9 and 12.1 +/- 6.8 micrograms/ml, respectively (P less than 0.01). The maximum elimination rate of phenytoin, estimated from steady state dose-concentration pairs, was significantly higher on the old formulation (9.5 +/- 2.8 vs. 7.2 +/- 1.1 mg/kg per day, P less than 0.025) even though there was no difference in the estimates of the Michaelis-Menten constant. The proportion of subtherapeutic levels on ostensibly equal doses fell from 85 to 45% on 300 mg/day of the two formulations (P less than 0.01), and to 28% on 400 mg/day of the new formulation. Steady state concentrations may be used to assess increased bioavailability of drugs with capacity-limited metabolism, such as phenytoin.
D000328:Adult; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009493:Neurosurgery; D010672:Phenytoin / Q000097:blood*
D010672:Phenytoin