| Bioavailability studies of drugs with nonlinear pharmacokinetics: I. Tracer dose AUC varies directly with serum concentration. | |
| | |
MedLine Citation:
|
PMID: 1487554 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
T R Browne; G K Szabo; G E Schumacher; D J Greenblatt; J E Evans; B A Evans |
Related Documents
:
|
19615934 - Interaction of phenylbutazone and colchicine in binding to serum albumin in rheumatoid ... 2330344 - Blood kinetics of sulfamonomethoxine and oxytetracycline following intrauterine spray i... 11289334 - Severe serum sickness-like reaction to oral penicillin drugs: three case reports. 2878604 - Cancer chemotherapy-induced tubular nephrotoxicity evaluated by immunochemical determin... 6782814 - Cultivation of m. leprae in cell-free, semi-synthetic media. 18999164 - A systematic review of medication safety and clinical outcomes related to drug interact... |
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 |
Affiliation:
|
Department of Neurology and Pharmacology, Boston University School of Medicine, MA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adolescent Adult Aged Biological Availability Epilepsy / drug therapy Humans Male Middle Aged Phenytoin / administration & dosage, blood, pharmacokinetics* |
| Grant Support | |
ID/Acronym/Agency:
|
HD-04147-14/HD/NICHD NIH HHS; HD-05515-13/HD/NICHD NIH HHS; NH-34223/NH/NIH HHS |
| Chemical | |
Reg. No./Substance:
|
57-41-0/Phenytoin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: A study in normal human volunteers to compare the rate and extent of levothyroxine absorption from S...
Next Document: Single-dose antibiotic therapy: what has the past taught us?