Pharmacokinetics of a low molecular weight heparin, logiparin, after intravenous and subcutaneous administration to healthy volunteers.
In six healthy volunteers we have estimated the pharmacokinetic parameters of the anti factor Xa (AXa) and anti factor IIa (AIIa) activities of a LMW heparin, Logiparin. For the AXa the following parameters were estimated in a 1-compartment model (mean and 95% confidence limits in brackets): elimination half life 82 minutes (60-127 min), absorption half life (s.c. inj.) 200 minutes (137-368 min), bioavailability 90% (24-156%), and apparent volume of distribution 3.9 l (3.1-5.2 l). The plasma activity was linearly correlated to the dose given and to the body weight of the volunteer. For the AIIa the parameters estimated in a 1-compartment model were: elimination half life 71 minutes (52-115 min), absorption half life 257 minutes (133-3442 min), bioavailability 67% (44-90%), and apparent volume of distribution 10.1 l (7.2-16.7 l). The plasma activity was dependent on dose and body weight but it also seemed to be influenced by individual factors. This study shows that the absorption rate is the rate limiting factor and the explanation for the long lasting effect of this LMW heparin after subcutaneous injection. The slow absorption rate and the high bioavailability are probably the major advantages of LMW heparins compared to conventional heparin.
Pedersen
P C
PC
Novo Nordisk A/S, Copenhagen, Denmark.
Ostergaard
P B
PB
Hedner
U
U
Bergqvist
D
D
Mätzsch
T
T
D000042:Absorption; D000328:Adult; D000704:Analysis of Variance; D001682:Biological Availability; D001835:Body Weight; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006493:Heparin / Q000008:administration & dosage / Q000493:pharmacokinetics; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D011897:Random Allocation
D006495:Heparin, Low-Molecular-Weight; D006493:Heparin