title: Influence of chlorthalidone on the pharmacokinetics and pharmacodynamics of Org 10172 (Lomoparan), a low molecular weight heparinoid, in healthy volunteers.
abstract: The influence of chlorthalidone (100 mg PO) on the pharmacokinetics and pharmacodynamics of Org 10172 (IV bolus injection of 3250 anti-Xa units), a low molecular weight heparinoid, was studied in six healthy male volunteers using an open randomized two-way crossover design. Chlorthalidone produced a slight decrease in clearance of anti-Xa activity from 7.1 +/- 1.0 to 6.6 +/- 0.8 mL/min and a decrease of the volume of distribution from 0.20 +/- 0.05 to 0.16 +/- 0.04 L/kg, whereas the volume of distribution of antithrombin activity increased from 0.14 +/- 0.05 to 0.26 +/- 0.10 L/kg (all differences P less than .05). During the entire study period no adverse events occurred. In summary, chlorthalidone showed separate effects on different fractions of Org 10172. The clinical implication of the slight change observed in plasma anti-Xa activity is likely to be limited, whereas the 80% increase in distribution volume of plasma antithrombin activity can not be defined as yet in terms of clinical relevance.
authors.affiliation: Center for Bio-Pharmaceutical Sciences, University of Leiden, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: de Boer
authors.forename: J C
authors.initials: JC
authors.lastname: Stiekema
authors.forename: M
authors.initials: M
authors.lastname: Danhof
authors.forename: D D
authors.initials: DD
authors.lastname: Breimer
mesh_terms: D000328:Adult; D001780:Blood Coagulation Tests; D002752:Chlorthalidone / Q000494:pharmacology*; D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D004347:Drug Interactions; D006025:Glycosaminoglycans / Q000493:pharmacokinetics* / Q000494:pharmacology; D006496:Heparinoids / Q000493:pharmacokinetics* / Q000494:pharmacology; D006497:Heparan Sulfate; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate
chemical_list: D002752:Chlorthalidone; D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D006025:Glycosaminoglycans; D006496:Heparinoids; D006497:Heparan Sulfate; C035838:danaparoid