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New Pharmacokinetic Methods: L Estimation of Mean Serum Concentration From Trough Serum Concentration
Author(s) -
Browne Thomas R.,
Greenblatt David J.,
Szabo George K.,
Evans James E.,
Evans Barbara A.
Publication year - 1990
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1990.tb03612.x
Subject(s) - pharmacokinetics , chemistry , serum concentration , half life , phenytoin , steady state (chemistry) , mean value , chromatography , medicine , mathematics , statistics , psychiatry , epilepsy
An equation is derived to estimate mean steady state serum concentration (C̄ ss ) from trough steady state serum concentration (C min ) which can be used for drugs with either linear or nonlinear pharmacokinetic properties. In 15 subjects receiving phenytoin monotherapy, estimated C̄ ss did not differ significantly from measured C̄ ss , while C min differed significantly ( P < .0001) from measured C̄ ss and estimated C̄ ss . Clearance (CL) and elimination half‐life (t 1/2 ) values determined by stable isotope tracer methods or by standard equations and measured C̄ ss or estimated C̄ ss did not differ significantly, while CL and t 1/2 values calculated with standard equations and C min differed significantly ( P < .02) from values obtained by any of the other three methods. We conclude: 1) C min values and CL and t 1/2 values calculated with C min values may differ significantly from C̄ ss values and CL and t 1/2 values calculated with C̄ ss ; 2) accurate estimates of C̄ ss and of CL and t 1/2 can be obtained using our procedure to correct a C min value to an estimated C̄ ss value.