Does alpha 1-acid glycoprotein reduce the unbound metabolic clearance of disopyramide in patients with renal impairment?
The pharmacokinetics of disopyramide was studied in 15 patients with renal dysfunction (4 with pyelonephritis, 7 with glomerular nephritis and 4 with interstitial nephritis). The elimination rate constant of unbound disopyramide was 0.094 h-1 and CLu/f (unbound clearance divided by bioavailability) was 245 ml/min. Both the unbound renal clearance (CLR) and CLu/f were highly correlated with the creatinine clearance (CLCR). The apparent unbound metabolic clearance in the patients was approximately two-fold lower than that previously reported in normal subjects. The estimated unbound metabolic clearance in the renal dysfunction patients showed a significant negative correlation with the alpha 1-acid glycoprotein (AAG) concentration and only a weak, non-significant correlation with CLCR. As AAG in the renal dysfunction subjects was increased in comparison with normal values, it is possible that AAG is a factor in the decrease in the apparent unbound metabolic clearance.
Braun
J
J
Institute of Nephrology, University of Erlangen-Nürnberg, Federal Republic of Germany.
Sörgel
F
F
Gluth
W P
WP
Oie
S
S
D000328:Adult; D000368:Aged; D003404:Creatinine / Q000097:blood / Q000652:urine; D004206:Disopyramide / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D005260:Female; D005921:Glomerulonephritis / Q000378:metabolism*; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009395:Nephritis, Interstitial / Q000378:metabolism*; D009961:Orosomucoid / Q000097:blood / Q000378:metabolism* / Q000652:urine; D011704:Pyelonephritis / Q000378:metabolism*
D009961:Orosomucoid; D003404:Creatinine; D004206:Disopyramide