Abstract | OBJECTIVE: DESIGN: Six adult subjects with cystic fibrosis and six healthy control subjects, matched by age and sex, were administered (R)- warfarin as a single intravenous bolus dose (0.375 mg/kg), and urine and plasma samples were collected for 192 hours. The concentration of (R)- warfarin in plasma and the concentration of (R)- warfarin and its metabolites in urine were determined by HPLC and GC/MS, respectively. Plasma protein binding of (R)- warfarin was measured by ultrafiltration. RESULTS: The unbound plasma clearance of (R)- warfarin was not significantly (p > 0.05) different between the cystic fibrosis and the control groups ( cystic fibrosis, 997 +/- 483 ml/hr/kg; control, 788 +/- 219 ml/hr/kg). The unbound metabolic clearances of (R)- warfarin to its oxidative metabolites--6-hydroxywarfarin, 7-hydroxywarfarin, 8-hydroxywarfarin, and 10-hydroxywarfarin (mediated by P450 3A4)--were also similar (p > 0.05) in the two groups (6-hydroxywarfarin: cystic fibrosis: 124.2 +/- 72.8 ml/hr/kg, control: 99.4 +/- 37.3 ml/hr/kg; 7-hydroxywarfarin: cystic fibrosis: 43.8 +/- 32.2 ml/hr/kg, control: 34.5 +/- 10.6 ml/hr/kg; 8-hydroxywarfarin: cystic fibrosis: 80.4 +/- 85.4 ml/hr/kg, control: 69.5 +/- 39.5 ml/hr/kg; 10-hydroxywarfarin: cystic fibrosis: 4.38 +/- 2.72 ml/hr/kg, control: 16.28 +/- 13.71 ml/hr/kg). CONCLUSION:
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Authors | J P Wang, J D Unadkat, S McNamara, T A O'Sullivan, A L Smith, W F Trager, B Ramsey |
Journal | Clinical pharmacology and therapeutics
(Clin Pharmacol Ther)
Vol. 55
Issue 5
Pg. 528-34
(May 1994)
ISSN: 0009-9236 [Print] United States |
PMID | 8181197
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Blood Proteins
- Warfarin
- Cytochrome P-450 Enzyme System
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Topics |
- Adult
- Blood Proteins
(metabolism)
- Cystic Fibrosis
(enzymology, metabolism)
- Cytochrome P-450 Enzyme System
(metabolism)
- Female
- Humans
- Male
- Protein Binding
- Stereoisomerism
- Warfarin
(metabolism, pharmacokinetics)
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