Pharmacokinetics and pharmacodynamics of dermatan sulfate after intravenous and intramuscular administration to healthy volunteers
Blardi, P.; Messa, G.L.; Urso, R.; Di Perri, T.
International Journal of Clinical Pharmacology Research 13(4): 231-238
1993
ISSN/ISBN: 0251-1649 PMID: 8150550 Document Number: 414719
The pharmacokinetics and pharmacodynamics of dermatan sulfate (DS) was investigated in healthy volunteers (two groups, namely group A: 6 subjects, group B: 8 subjects). The subjects of group A received 100 mg of DS both i.v. and i.m. and the subjects of group B received 400 mg of DS both i.v. and i.m. in two different days. The resulting anticoagulant activities were assessed by the activated partial thromboplastin time (aPTT) and the pharmacokinetic parameters were calculated from the plasma concentrations of DS measured by a chromogenic assay. The plasma concentrations of DS were fitted by linear and non-linear elimination models (i.e. assuming that the drug elimination follows Michaelis-Menten kinetics). Some evidence of non-linear kinetics was given by the observation that the mean terminal half-life and clearance estimated by the linear model were not independent of the i.v. dose (0.83 +- 0.1 and 1.74 +- 0.21 hours and 4.94 +- 0.64 and 2.67 +- 0.27 l/h after 100 and 400 mg i.v. respectively). Moreover the mean half-lives estimated after i.m. administrations were much higher than the values estimated after the i.v. dose (2.03 +- 0.74 and 3.54 +- 1.3 hours after 100 and 400 mg) and linear models failed to fit simultaneously the DS plasma concentrations after both the administration routes. Using the linear model, the mean drug bioavailability after i.m. administration was estimated to be about 30% and 80% after the 100- and the 400-mg dose respectively. Assuming a complete drug bioavailability after i.m. administration, the non-linear elimination mode/interpolated well with the DS plasma concentrations, fitting simultaneously the i.v. and the i.m. data. No side-effects were recorded during the study, and routine biochemical and hematological parameters remained unchanged at the end of the study.