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Does alpha1-acid glycoprotein reduce the unbound metabolic clearance of disopyramide in patients with renal impairment?

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Summary

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 α1-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.

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Authors and Affiliations

  1. Institute of Nephrology, University of Erlangen-Nürnberg, Nürnberg, Federal Republic of Germany

    J. Braun

  2. IBMP, Institute for Biomedical and Pharmaceutical Research, Nürnberg, Federal Republic of Germany

    F. Sörgel

  3. Institute of Forensic Medicine, University of Erlangen-Nürnberg, Erlangen, Federal Republic of Germany

    W. P. Gluth

  4. Department of Pharmacy, University of California, San Francisco, USA

    S. Øie

Authors
  1. J. Braun
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  2. F. Sörgel
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  3. W. P. Gluth
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  4. S. Øie
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Braun, J., Sörgel, F., Gluth, W.P. et al. Does alpha1-acid glycoprotein reduce the unbound metabolic clearance of disopyramide in patients with renal impairment?. Eur J Clin Pharmacol 35, 313–317 (1988). https://doi.org/10.1007/BF00558271

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  • DOI: https://doi.org/10.1007/BF00558271

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