Linked Life Data

10496299

Source:http://linkedlifedata.com/resource/pubmed/id/10496299

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1999-11-4
pubmed:abstractText
Troglitazone is a new thiazolidinedione oral antidiabetic agent approved for use to improve glycaemic control in patients with type 2 diabetes. It is rapidly absorbed with an absolute bioavailability of between 40 and 50%. Food increases the absorption by 30 to 80%. The pharmacokinetics of troglitazone are linear over the clinical dosage range of 200 to 600 mg once daily. The mean elimination half-life ranges from 7.6 to 24 hours, which facilitates a once daily administration regimen. The pharmacokinetics of troglitazone are similar between patients with type 2 diabetes and healthy individuals. In humans, troglitazone undergoes metabolism by sulfation, glucuronidation and oxidation to form a sulfate conjugate (M1), glucuronide conjugate (M2) and quinone metabolite (M3), respectively. M1 and M3 are the major metabolites in plasma, and M2 is a minor metabolite. Age, gender, type 2 diabetes, renal impairment, smoking and race do not appear to influence the pharmacokinetics of troglitazone and its 2 major metabolites. In patients with hepatic impairment the plasma concentrations of troglitazone, M1 and M3 increase by 30%, 4-fold, and 2-fold, respectively. Cholestyramine decreases the absorption of troglitazone by 70%. Troglitazone may enhance the activities of cytochrome P450 (CYP) 3A and/or transporter(s) thereby reducing the plasma concentrations of terfenadine, cyclosporin, atorvastatin and fexofenadine. It also reduces the plasma concentrations of the oral contraceptive hormones ethinylestradiol, norethindrone and levonorgestrel. Troglitazone does not alter the pharmacokinetics of digoxin, glibenclamide (glyburide) or paracetamol (acetaminophen). There is no pharmacodynamic interaction between troglitazone and warfarin or alcohol (ethanol). Pharmacodynamic modelling showed that improvement in fasting glucose and triglyceride levels increased with dose from 200 to 600 mg. Knowledge of systemic troglitazone exposure within a dose group does not improve the prediction of glucose lowering response or adverse effects beyond those based on the administered dose.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0312-5963
pubmed:author
pubmed:issnType
Print
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
91-104
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Clinical pharmacokinetics of troglitazone.
pubmed:affiliation
Department of Pharmacokinetics, Dynamics and Metabolism, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan 48105, USA. CHO-MING.LOI@WL.COM
pubmed:publicationType
Journal Article, Review