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Antimicrobial Agents and Chemotherapy, May 1996, 1134-1138, Vol 40, No. 5
JF Flaherty Jr, G Gatti, J White, J Bubp, M Borin and JG Gambertoglio
Patients with AIDS have altered pharmacokinetics of clindamycin compared
with those of healthy control subjects. In an attempt to better understand
these differences, we undertook a study of protein binding of clindamycin
in sera of patients with AIDS. Fifteen patients with AIDS and 15 healthy
volunteers were given a single 600-mg dose of clindamycin orally and
intravenously, and serum samples were collected at three time points
corresponding to high, midpoint, and low clindamycin concentrations.
Protein binding was determined by ultrafiltration, and total and unbound
clindamycin concentrations were measured with a gas chromatography assay.
AIDS patients had alpha 1- acid glycoprotein values approximately twice
those of healthy volunteers (mean +/- standard deviation, 103 +/- 27 versus
61 +/- 11 mg/dl; P = 0.001). Overall, serum protein binding levels were
higher in AIDS patients (mean +/- standard deviation, 83 +/- 7 versus 78%
+/- 8%; P = 0.0001), which is likely the result of increased alpha 1-acid
glycoprotein levels in these patients. Total concentrations of clindamycin
in plasma were significantly higher in AIDS patients at most time points
studied, while unbound serum clindamycin concentrations did not differ
among the groups at each sampling time after both oral and intravenous
dosing. Increased protein binding may partly explain the altered
pharmacokinetic disposition of clindamycin in AIDS patients; however, other
factors cannot be excluded.
Copyright © 1996 by the American Society for Microbiology. All rights reserved.
Protein binding of clindamycin in sera of patients with AIDS
Division of Clinical Pharmacy, School of Pharmacy, University of California, San Francisco 94143-0622, USA. jffj@itsa.ucsf.edu
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