The pharmacokinetics and bioavailability of subcutaneously administered dihydroergotamine, heparin and the dihydroergotamine-heparin combination.
Thromb Res
; 31(1): 51-67, 1983 Jul 01.
Article
em En
| MEDLINE
| ID: mdl-6612697
ABSTRACT
Subcutaneously administered dihydroergotamine (DHE) becomes rapidly and completely available to the human systemic circulation, with peak plasma levels of 1.4-3.5 ng/mL/mg achieved in less than 1 h. The elimination of DHE from plasma is biphasic, t 1/2 alpha = 1h, t 1/2 beta = 4-5 h. DHE exhibits linear dose proportionality. Coadministration of heparin results in a statistically significant increase of 25% in the area under the plasma level/time curve for DHE (bioavailability). Coinjection of DHE and heparin in the same subcutaneous site furthermore causes a decrease in the rate of DHE absorption by 63%, resulting in delayed time to peak (by 110%) and reduced peak levels (by 15%) of DHE. In contrast, there is no effect by coadministered DHE on heparin pharmacokinetic parameters. Heparin peak plasma levels (0.3 I.U./mL by activated factor X, 0.1 I.U./mL by protamine titration with a 15,000 I.U. s.c. bolus) are achieved in 3.6 h. Pharmacokinetic analysis suggests that the subcutaneous route of administration provides only 19% of the bioavailable heparin that would be obtained following administration of an equipotent intravenous dose. DHE-heparin formulated for injection in combination demonstrates systemic availability identical to that of the two components injected separately, but with a reduced rate of absorption for the DHE component and a corresponding attenuation of fluctuations in steady state DHE levels.
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Base de dados:
MEDLINE
Assunto principal:
Heparina
/
Di-Hidroergotamina
Limite:
Adult
/
Humans
/
Male
/
Middle aged
Idioma:
En
Ano de publicação:
1983
Tipo de documento:
Article