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Ex Vivo Protein Binding of Clindamycin in Sera With Normal and Elevated α 1 ‐Acid Glycoprotein Concentrations
Author(s) -
Kays Michael B.,
White Roger L.,
Gatti Giorgio,
Gambertoglio John G.
Publication year - 1992
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1002/j.1875-9114.1992.tb02671.x
Subject(s) - radial immunodiffusion , orosomucoid , chemistry , acute phase protein , clindamycin , blood proteins , pharmacokinetics , in vivo , ultrafiltration (renal) , antibiotics , chromatography , glycoprotein , medicine , immunology , biochemistry , biology , antibody , inflammation , microbiology and biotechnology
Clindamycin is a lincosamide antibiotic that binds primarily to α 1 ‐acid glycoprotein (AAG), an acute‐phase serum protein. Many studies have shown that AAG concentrations increase in response to stress, including infection, myocardial infarction, and trauma. The objectives of this study were to determine the serum protein binding of various clindamycin concentrations in sera with normal and elevated AAG concentrations. Serum was obtained from 4 healthy volunteers and 12 patients with pathophysiologic conditions known to elevate serum AAG concentrations. Timing for collection was determined from the literature, corresponding with the expected peak concentration for each disease state. Samples were assayed for AAG by radial immunodiffusion and were spiked with clindamycin to achieve total concentrations of 10 μg/ml (n = 18), 4 μg/ml (n = 10), and 2 μg/ml (n = 7). Protein binding was determined by ultrafiltration and subsequent high‐performance liquid or gas chromatography. Protein binding was dependent on the serum concentrations of both AAG and clindamycin. When AAG concentrations increased from 101–150 mg/dl to 201 mg/dl or greater, mean protein binding increased from 81.2% to 92.4% (p = 0.1265) and from 61.3% to 88.6% (p < 0.05) at clindamycin concentrations of 2 and 4 μg/ml, respectively. With AAG concentrations between 101 and 150 mg/dl, mean protein binding increased from 62.4% at 10 μg/ml to 81.2% at 2 μg/ml (p = 0.1514). Since AAG concentrations may increase in certain patients, the concentration of free (pharmacologically active) drug may fall below the minimum inhibitory concentration for several pathogens earlier in a dosing interval.