Document Detail


Biopharmaceutical aspects of tolfenamic acid.
MedLine Citation:
PMID:  7816776     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The pharmacokinetics of tolfenamic acid is well described by a two-compartment model with relatively short half-lives (T/2 beta 1-2 hours) and tolfenamic acid is highly protein-bound with small volumes of distribution. It is cleared relatively fast (150-200 ml/min), mainly by hepatic metabolism and the metabolites are renally cleared as glucuronic acid conjugates. The peroral absorption is good and the peroral bioavailability is about 75%, as first pass metabolism accounts for about 20%. Tolfenamic acid shows linear pharmacokinetics and during multiple dosage regimen, i.e. thrice daily, no accumulation beyond the second dose is observed. The bioavailability in dependence of age and disease has been studied and only in the case of severe liver or kidney impairment, a change in dosage regimen seems warranted. The development of different formulations will be outlined, mainly on rectal delivery, on sustained release and rapid release oral formulations, on topical ointment, and on parenteral delivery. The problems with tolfenamic acid in pharmaceutical formulation caused mainly by poor solubility will be discussed. Formulations ready for the market now or very soon are Clotam capsules (tablets). Clotam retard tablets, Clotam suppositories, and Clotam oral suspension, whereas rapid tablets, topical ointments, and parenteral formulations need further development to be ready for marketing in the years to come.
Authors:
S B Pedersen
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Pharmacology & toxicology     Volume:  75 Suppl 2     ISSN:  0901-9928     ISO Abbreviation:  Pharmacol. Toxicol.     Publication Date:  1994  
Date Detail:
Created Date:  1995-02-06     Completed Date:  1995-02-06     Revised Date:  2005-11-17    
Medline Journal Info:
Nlm Unique ID:  8702180     Medline TA:  Pharmacol Toxicol     Country:  DENMARK    
Other Details:
Languages:  eng     Pagination:  22-32     Citation Subset:  IM    
Affiliation:
A/S GEA Farmaceutisk Fabrik, Biochemical Department, Hvidovre, Denmark.
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MeSH Terms
Descriptor/Qualifier:
Absorption
Aging / metabolism
Anthranilic Acids / pharmacokinetics*
Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics*
Arthritis, Rheumatoid / metabolism
Biological Availability
Dosage Forms
Drug Administration Routes
Half-Life
Humans
Liver Cirrhosis / metabolism
Migraine Disorders / metabolism
Chemical
Reg. No./Substance:
0/Anthranilic Acids; 0/Anti-Inflammatory Agents, Non-Steroidal; 0/Dosage Forms; 13710-19-5/tolfenamic acid

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