Plasma Protein Binding and Renal Clearance

As only unbound drug is available for renal clearance by filtration at the glomerulus, drugs with high plasma protein binding will only appear slowly in the filtrate. Hence considerations of the renal clearance process based on total drug concentrations either in plasma or urine may be misleading. 

However, the major contributing factor to the decreased renal clearance of total drug was increasing plasma protein binding with increasing lipophilicity. When the extent of plasma protein binding was taken into account, the imbound renal clear- 

The value for unbound renal clearance of 6 mL min kg is in excess of GFR in the dog ( 4 mL min kg ) indicating a degree of tubular secretion in the renal clearance of these basic molecules (pKa values of 7.8-8.2). The unbound renal clearance of compound 4 is about 1.5 mL min kg and indicates substantial tubular reabsorption of this, the most lipophilic member of the series. This compound is also substantially less basic than the others (ipK of 7.3) and as such may be subject to reduced tubular secretion. 

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