RT Journal Article
SR Electronic
T1 Effect of Hypoalbuminemia on the Disposition of Theophylline
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 595
OP 597
VO 26
IS 6
A1 Nakura, Hironori
A1 Tateishi, Tomonori
A1 Watanabe, Minoru
A1 Asoh, Masako
A1 Tanaka, Masami
A1 Kumai, Toshio
A1 Kobayashi, Shinichi
YR 1998
UL http://dmd.aspetjournals.org/content/26/6/595.abstract
AB We demonstrated the effect of hypoalbuminemia on theophylline disposition in rats. The pharmacokinetic parameters in Sprague-Dawley rats (SDRs) were compared with those in spontaneously hyperlipidemic rats (HLRs), which had approximately one half the serum albumin concentration of the SDRs, after a single 10 mg/kg injection (iv) of theophylline. Theophylline clearance (CL) in the HLRs was increased 1.6-fold, and the AUC was decreased by 36%. Although the elimination t½ was not significantly different between the two types of rats, the distribution volume (Vd ) was increased significantly in the HLRs, compared with the SDRs. The free theophylline concentration in the SDRs was one half of the total concentration. In contrast, the free theophylline concentration in the HLRs was approximately equal to the total concentration. The enzymatic activities and apoprotein expression levels of CYP1A were decreased significantly in the HLRs, compared with the SDRs. The total theophylline CL was increased in HLRs with hypoalbuminemia, even though they exhibited lower enzymatic activity and CYP1A expression than did the SDRs. Because the unbound fraction andVd of theophylline in HLRs were much larger than those in SDRs, we conclude that hypoalbuminemia may contribute to an increase in the Vd and a decrease in the CL for theophylline. The American Society for Pharmacology and Experimental Therapeutics