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Significance of error associated with use of the one‐compartment formula to calculate clearance of thirty‐eight drugs
Author(s) -
Dvorchik Barry H.,
Vesell Elliot S.
Publication year - 1978
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/cpt1978236617
Subject(s) - theophylline , tolbutamide , drug , phenytoin , medicine , chlordiazepoxide , pharmacology , hexobarbital , pentobarbital , diazepam , anesthesia , chemistry , biochemistry , psychiatry , epilepsy , insulin , enzyme , microsome
A survey of the literature was performed to gather information on the magnitude of the error introduced into calculating drug clearance by using a one‐compartment formula for drugs whose disposition follows multicompartment kinetics. Sufficient data to permit quantitation of this error were found for 38 drugs. The magnitude of the error varied widely depending on the initial distribution of the particular drug. Antipyrine and such commonly used drugs as amobarbital, chlordiazepoxide, nortriptyline, pentobarbital, phenytoin, sulfisoxazole, theophylline, tolbutamide, and warfarin had errors of 8% or less, thereby permitting utilization of the one‐compartment formula for determination of drug clearances without much loss of accuracy. However, 22 drugs exhibited errors ranging from 12% to 196%; for these drugs, the one‐compartment formula introduced considerable inaccuracy. The errors for diazepam, meperidine, and propranolol, when administered to patients with hepatic cirrhosis or to hypertensive patients, were 4%, 5%, and 6%, respectively, whereas in normal subjects the errors were 18%, 14%, and 2/%. Thus, the clinical status of the subject may influence the choice of the model used. On the basis of these data we conclude that for many commonly used drugs the one‐compartment formula is acceptable for determining drug clearance, loading dose, or maintenance dose.