Pharmacokinetics of heparin and related polysaccharides

Journal Article · Sun Jan 01 04:00:00 EST 1989 · Ann. N.Y. Acad. Sci.; (United States)

DOI:https://doi.org/10.1111/j.1749-6632.1989.tb22510.x· OSTI ID:5934215

Boneu, B; Dol, F; Caranobe, C; Sie, P; Houin, G

The pharmacodynamic profile of standard heparin (SH), a low molecular weight derivative (CY 216) and of dermatan sulfate (DS), a new potential antithrombotic drug, was investigated in the rabbit over a large range of doses. After bolus i.v. injection of low doses, the biological activity of SH disappeared exponentially; however, its half-life was prolonged when the dose injected increased, and over 158 micrograms/kg (100 anti-factor Xa U/kg) the biological activity disappeared as a concave-convex curve. CY 216 disappeared more slowly than SH at low doses but faster than SH at higher doses. More than 90% of the DS biological activity present 1 minute after the i.v. injection disappeared exponentially without dose-dependent effects. Increasing doses of the three drugs were then delivered for 5 h under continuous infusions. Below 500 micrograms/kg/h the DS and CY 216 plateau concentrations were higher than that of SH while above this dose the SH concentration was higher than that of DS and CY 216. These observations may be explained by the results of pharmacokinetics experiments where /sup 125/I-labeled compounds were delivered by bolus i.v. injection in association with increasing doses of their unlabeled counterparts. For SH there was a 10-fold difference between the half-life of the lower dose (32 micrograms/kg or 5 anti-factor Xa U/kg) and that of the higher dose (3200 micrograms/kg); it was demonstrated that the half-life of SH continuously shortened as its plasma concentration decreased. In contrast the CY 216 and DS half-lives were very close, independent of the dose delivered, and therefore longer than that of SH at low doses and shorter than that of SH at higher doses.

• Research Organization: Centre de Transfusion Sanguine, Toulouse (France)
• OSTI ID: 5934215
• Journal Information: Ann. N.Y. Acad. Sci.; (United States), Journal Name: Ann. N.Y. Acad. Sci.; (United States) Vol. 556; ISSN ANYAA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINES
ANIMALS
ANTICOAGULANTS
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL HALF-LIFE
CARBOHYDRATES
CHONDROITIN
COMPARATIVE EVALUATIONS
DAYS LIVING RADIOISOTOPES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ENZYMES
HEMATOLOGIC AGENTS
HEPARIN
HYDROLASES
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
MAMMALS
MEDICINE
MOLECULAR WEIGHT
MUCOPOLYSACCHARIDES
NEPHRECTOMY
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
OXYGEN COMPOUNDS
PEPTIDE HYDROLASES
POLYSACCHARIDES
RABBITS
RADIOISOTOPES
REACTION KINETICS
SACCHARIDES
SERINE PROTEINASES
SULFATES
SULFUR COMPOUNDS
SURGERY
TRACER TECHNIQUES
VERTEBRATES