Interplay Between Metabolic and Renal Clearance

Small molecules, with relatively low molecular weight, will appear in the urine due to glomerular filtration. The secretion of drugs into the urine can also occur through tubular carrier systems similar to those present on the sinusoid face of the hepatocyte. For instance, of the carriers illustrated in Figure 5.2, Natp, OATP and OCT1 are also present in the kidney. In addition another organic cation transporter, OCT2, is also present. There is also a vast difference in the volume of fluid formed at the glomerulus each minute and the amount that arrives during the same period at the collecting tubule. The aqueous concentration processes that occur in the kidney mean that for drugs capable of travelling through the lipid core of the tubule membrane, significant reabsorption back into the plasma will occur. The end result of this process is that only hydrophilic molecules are voided in the urine to any substantial degree. This interaction between metabolism and renal clearance can be illustrated by following the fate of the cholinesterase inhibitor SM-10888 [3]. A number of metabolism processes occur on the lipophilic parent molecule involving phase 1 oxidation and phase 2 conjugation reactions. Some of these processes occur sequentially as illustrated in Figure 5.5.

Fig. 5.5 Metabolism of SM-10888, involving phase 1 and phase 2 metabolic processes.

5.4 Role of Lipophilicity in Drug Clearance 63

5.4 Role of Lipophilicity in Drug Clearance 63

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