TY - JOUR
T1 - Gentamicin and phenytoin sieving through hollow-fiber polysulfone hemofilters
AU - Golper, T. A.
AU - Saad, A. M.A.
AU - Morris, C. D.
N1 - Funding Information:
viding the minifilters used in this study, Walt Amacher and the dialysis unit staff for technical help, and 'l'erry Green and William M. Bennett for advice. Dr. Saad's fellowship and research were sponsored by a grant from AmidEast.
PY - 1986
Y1 - 1986
N2 - The sieving characteristics of the prototype drugs gentamicin (poorly protein bound) and phenytoin (highly protein bound) were measured in vitro using polysulfone capillary hemofilters similar to those used in clinical continuous arteriovenous hemofiltration. Plasma water, whole plasma, and whole blood were the solvent systems used with variable drug concentrations and solvent flow rates. Our results indicate that the sieving coefficients for both drugs can be accurately defined as the concentration in the ultrafiltrate divided by the concentration in the artery. This correlates with a more rigorously derived expression by Colton and Henderson (r = 0.98, P < 0.00001 for both drugs) and avoids the necessity of measuring venous concentrations. Drug sieving in the three solvents followed expectations from known protein-binding data and was independent of solvent flow rate. For both drugs, at higher drug concentrations sieving increased in plasma, consistent with the saturation of protein-binding sites. In whole blood, sieving fell for both drugs with increasing drug concentrations, consistent with drug compartmentalization into red blood cells. Although these sieving changes with increasing drug concentrations were statistically significant, their clinical significance is doubtful. Phenytoin sieving in plasma was increased by the addition of free fatty acids, consistent with a protein-drug displacement effect. There appears to be a real, but small, effect of protein concentration polarization, protein-membrane and drug-membrane interactions on drug sieving. Our observations are consistent with the expectation that the major determinant of drug sieving is the extent of drug-protein binding.
AB - The sieving characteristics of the prototype drugs gentamicin (poorly protein bound) and phenytoin (highly protein bound) were measured in vitro using polysulfone capillary hemofilters similar to those used in clinical continuous arteriovenous hemofiltration. Plasma water, whole plasma, and whole blood were the solvent systems used with variable drug concentrations and solvent flow rates. Our results indicate that the sieving coefficients for both drugs can be accurately defined as the concentration in the ultrafiltrate divided by the concentration in the artery. This correlates with a more rigorously derived expression by Colton and Henderson (r = 0.98, P < 0.00001 for both drugs) and avoids the necessity of measuring venous concentrations. Drug sieving in the three solvents followed expectations from known protein-binding data and was independent of solvent flow rate. For both drugs, at higher drug concentrations sieving increased in plasma, consistent with the saturation of protein-binding sites. In whole blood, sieving fell for both drugs with increasing drug concentrations, consistent with drug compartmentalization into red blood cells. Although these sieving changes with increasing drug concentrations were statistically significant, their clinical significance is doubtful. Phenytoin sieving in plasma was increased by the addition of free fatty acids, consistent with a protein-drug displacement effect. There appears to be a real, but small, effect of protein concentration polarization, protein-membrane and drug-membrane interactions on drug sieving. Our observations are consistent with the expectation that the major determinant of drug sieving is the extent of drug-protein binding.
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U2 - 10.1038/ki.1986.276
DO - 10.1038/ki.1986.276
M3 - Article
C2 - 3820943
AN - SCOPUS:0022892536
SN - 0085-2538
VL - 30
SP - 937
EP - 943
JO - Kidney International
JF - Kidney International
IS - 6
ER -