Protein binding of clindamycin in sera of patients with AIDS

Abstract

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.