Elimination of non-reactive and weakly reactive human α1-acid glycoprotein after induction of the acute phase response in rats

Author:

Parivar Kourosh1,Tolentino Lorna1,Taylor Glyn2,øie Svein1

Affiliation:

1. Department of Pharmacy, School of Pharmacy, University of California, San Francisco, CA 94143–0446, USA

2. Department of Pharmacy, Welsh School of Pharmacy, University of Wales, Cardiff CF1 3XF, UK

Abstract

Abstract The disposition of concanavalin A (Con A)-non-reactive and Con A-reactive human α1-acid glycoprotein (AAG) was studied in normal male rats and in acute phase response-activated male rats. Activation of the acute phase response was made using a subcutaneous administration of ethynyloestradiol in sesame oil. This technique increased the endogenous AAG concentration 7-fold. In control rats the two forms of human AAG showed identical kinetics with an average clearance of 5·4 mL h−1 kg−1, terminal half-life of 13·5 h and a volume of distribution (steady state) of 91 mL kg−1. In the acute phase response-activated animals, both the clearance and volume of distribution were larger: the average clearance of the Con A-non-reactive AAG was 10·2 mL h−1 kg−1, the volume of distribution (steady state) 152 mL kg−1 and the terminal half-life 11·7 h. The Con A-reactive AAG had a clearance of 14·7 mL h−1 kg−1, a volume of distribution (steady state) of 262 mL kg−1 and a half-life of 15·8 h. The results indicate that not only does activation of the acute phase response alter the kinetics of AAG but that the change is different for the different types of AAG.

Funder

NIH

Publisher

Oxford University Press (OUP)

Subject

Pharmaceutical Science,Pharmacology

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