Document Detail

Bioavailability studies of drugs with nonlinear pharmacokinetics: I. Tracer dose AUC varies directly with serum concentration.
MedLine Citation:
PMID:  1487554     Owner:  NLM     Status:  MEDLINE    
The authors show that for a drug cleared by one enzyme the area under the serum concentration-time curve from time 0 to infinity (AUC0-INF) of a test dose can be expressed as AUC0-INF = TD x F x (Km + C)/Vmax where TD is test dose size, F is fraction absorbed, C is drug serum concentration at the time of the study, and Km and Vmax are the Michaelis constant and maximum velocity of the enzyme. This equation predicts the AUC0-INF produced by a given tracer dose of drug will vary directly with C in drugs with nonlinear pharmacokinetic properties (i.e., drugs whose value for C approaches or exceeds Km) if C is held constant by administration of tracer and maintenance doses of drug. The AUC0-INF produced by intravenous tracer doses of 150 mg of 13C15N2-sodium phenytoin was determined in 15 subjects at 30 different values of C. AUC0-INF showed a high degree of direct linear correlation with C (AUC0-INF (ug x hr/mL) = 35.4 + 8.1 x C (ug/mL), r = 0.885, P < .0001). Consequences of this observation for relative bioavailability studies of drugs with nonlinear pharmacokinetic properties are discussed.
T R Browne; G K Szabo; G E Schumacher; D J Greenblatt; J E Evans; B A Evans
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of clinical pharmacology     Volume:  32     ISSN:  0091-2700     ISO Abbreviation:  J Clin Pharmacol     Publication Date:  1992 Dec 
Date Detail:
Created Date:  1993-02-24     Completed Date:  1993-02-24     Revised Date:  2012-10-23    
Medline Journal Info:
Nlm Unique ID:  0366372     Medline TA:  J Clin Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1141-5     Citation Subset:  IM    
Department of Neurology and Pharmacology, Boston University School of Medicine, MA.
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MeSH Terms
Biological Availability
Epilepsy / drug therapy
Middle Aged
Phenytoin / administration & dosage,  blood,  pharmacokinetics*
Grant Support
Reg. No./Substance:

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