Covariance Analysis of Laboratory Variance in Steady-State Serum Phenytoin Concentrations

Hanan Costeff, Zeev Groswasser, Nachum Soroker, Gerald van Belle

Research output: Contribution to journalArticlepeer-review


Inpatients (n = 57) on long term prophylaxis with 2 oral phenytoin preparations were followed up via monthly checks of serum drug concentrations. Duplicate serum aliquots were submitted to 2 laboratories, and covariance analysis was used to estimate laboratory error. The laboratory-associated variance of examinations using the ‘EMIT’ or ‘TDX’ systems was 7.1 to 10 (mg/L)2, while that of chromatographic assays was 37.1 (mg/L)2. Laboratory errors were distributed in a non-normal fashion. The ratio of the maximum rate of metabolism (Vmax) and the Michaelis-Menten constant (Km) tended to remain constant between individuals. A linear analytical model showed little more residual variance than one based on Michaelis-Menten pharmacokinetics.

Original languageEnglish
Pages (from-to)331-335
Number of pages5
JournalClinical Pharmacokinetics
Issue number4
StatePublished - Apr 1991


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