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1 The percentage of unbound drug was slightly higher in both moderately impaired cohorts.
2 The pharmacodynamic relationship between unbound drug concentration and QT prolongation was fit by a simple linear model.
3 Arthritic rats exhibited lower plasma and ISF albumin concentrations and reduced clearances of unbound drug to explain pharmacokinetic profiles.
4 The net effect of chronic inflammation was an elevation of the C max and area under the plasma concentration-time curve (AUC) of unbound drug .
5 A trend was observed toward more severe hematologic toxicity with the 3-hour schedule (P =.053), consistent with increased exposure to unbound drug .
6 Unbound drug is the pharmacodynamically relevant concentration.
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