ABSTRACT
This Chapter includes a comprehensive evaluation of renal excretion and its role in the pharmacokinetics (PK) and toxicokinetics (TK) of xenobiotics. The contents include the major functions of the kidney that influence the excretion of unchanged xenobiotic and elimination of its metabolites from the body. The aspects of glomerular filtration, tubular reabsorption, and secretion of the nephron relevant to the PK-TK analysis, the significance of the proximal tubule in reabsorption and metabolism of xenobiotics, the significance of the loop of Henle and distal tubule and collecting duct in shaping the excretion of xenobiotics are examined. The exogenous markers and endogenous biomarkers for the estimation of the glomerular filtration, including the radiolabeled markers, inulin, iohexol, creatinine, cystatin C and the related empirical equations for estimation of glomerular filtration rate (GFR) are discussed in detail. The PK-TK analysis of urinary excretion of unchanged xenobiotic, eliminations of the metabolite(s), related computational methodologies such as the Rate plot and ARE plot (amount remaining to be excreted) for both unchanged and metabolite using various models and dosing administration like bolus, first-order absorption, and zero-order input, with all related equations, figures and assumptions including the general equations of PK/TK multicompartmental model, mechanistic models, and the non-compartmental approaches for analysis of urinary data are expanded and discussed in this Chapter. The renal metabolism of xenobiotics, as an important site of metabolism in the body after the liver, its most important enzymes of phase I and phase II metabolism are the next topics of the Chapter. The contents conclude with the section on renal replacement therapy, approaches, and methodologies and the effect of the hemodialysis therapy on the PK-TK parameters and rate constants.
