title: Nycthemeral variations of 99Tcm-labelled heparin pharmacokinetic parameters.
abstract: Six healthy volunteers (5 males and one female) received four i.v. boluses of 160 U.I. of 99Tcm-heparin at 8.00, 14.00, 20.00 and 02.00 hours at seven-day intervals. Nine blood samples were taken covering a period of 2 h after administration. Simultaneously urine was collected and diuresis was noted. Plasma and urinary radioactivity were measured and standard pharmacokinetic parameters were calculated. Nycthemeral variations of these kinetic parameters were detected by means of distribution-free tests. Circadian rhythms (period = 24 h) were analysed by means of the cosinor method and the Gauss-Marquardt method. The mean raw value of the following parameters: apparent volume of distribution, plasmatic clearance and extra-renal metabolic clearance, increased significantly between 8.00 and 14.00 (p less than 0.01) and decreased between 14.00 and 20.00 (p less than 0.05). A circadian rhythm was found for the plasmatic clearance only (p less than 0.04). On the other hand the elimination half-lives and the renal clearance were unaffected by the time of the injections. These results obtained for low doses of 99Tcm-heparin suggest a circadian rhythm of the bio-availability of heparin in man. This fact should be taken into account for the use of 99Tcm-heparin in the diagnosis of deep-vein thrombosis and for the safe adjustment of the heparin dosages in the treatment of severe thromboembolism.
mesh_terms: D002940:Circadian Rhythm; D004231:Diuresis; D005260:Female; D006207:Half-Life; D006493:Heparin / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D015609:Organotechnetium Compounds; D013667:Technetium / Q000378:metabolism
chemical_list: D015609:Organotechnetium Compounds; C047074:technetium Tc 99m heparin; D013667:Technetium; D006493:Heparin