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Individualization of phenytoin dosage regimens
Author(s) -
Ludden Thomas M.,
Allen John P.,
Valutsky William A.,
Vicuna Ana V.,
Nappi Jean M.,
Hoffman Stephen F.,
Wallace Jack E.,
Lalka David,
McNay John L.
Publication year - 1977
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt1977213287
Subject(s) - phenytoin , nomogram , pharmacokinetics , anticonvulsant , medicine , dosing , serum concentration , steady state (chemistry) , pharmacology , chemistry , epilepsy , psychiatry
Two methods for arriving at optimum, individual phenytoin dosage regimens have been evaluated in 12 patients. (1) Individual Michaelis‐Menten pharmacokinetic parameters for phenytoin were estimated from two reliable steady‐state phenytoin serum concentrations resulting from different daily doses: The observed steady‐state phenytoin serum levels obtained after 3 to 8 wk of compliance with dosage regimens calculated from the individual pharmacokinetic parameters agreed well with predicted levels (r = 0.824, p < 0.02). The average deviation between observed and predicted levels was 0.04 µg/ml (range, ±3.2 µg/ml). (2) A previously published nomogram for making adjustments in phenytoin dosage regimens: The serum phenytoin concentration actually expected from the dose indicated by the nomogram was calculated using individual pharmacokinetic parameters. The daily dose for one patient would have exceeded his estimated maximal rate of metabolism. The correlation between calculated and predicted phenytoin serum levels in the other 11 patients was weak but significant (r = 0.360, p < 0.05). The average deviation was −3 µg/ml (range, 3.9 to −11.3 µg/ml). It was concluded that the use of individual pharmacokinetic parameters is practical and is also superior to the nomogram.