Renal excretion, of drugs

The renal excretion of drugs depends on glomerular filtration, tubular secretion, and tubular absorption. A twofold increase in glomerular filtration occurs in the first 14 days of life [36], The glomerular filtration rate continues to increase rapidly in the neonatal period and reaches a rate of about 86 mL/min per 1.73 m2 by 3 months of age. Children 3-13 years of age have an average clearance of 134 mL/min per 1.73 m2 [37]. Tubular secretion approaches adult values between 2 and 6 months [11], There is more variability observed in maturation of tubular reabsorption capacity. This is likely linked to fluctuations in urinary pH in the neonatal period [38],... 

Interference with renal excretion of drugs that undergo active tubular secretion, especially weak acids. Inhibition of glucuronide conjugation of other drugs. 

Interference with renal excretion of drugs that undergo active tubular secretion. Salicylate renal excretion dependent on urinary pH when large doses of salicylate used. Aspirin (but not other salicylates) interferes with platelet function. Large doses of salicylates have intrinsic hypoglycemic activity. 

Drugs that alter the pH of urine can significantly affect the renal excretion of other drugs. Acid urine increases the effectiveness of mercurial diuretics. It also accelerates the excretion of basic drugs such as meperidine, tricyclic antidepressants, amphetamines, and antihistamines. Acidic drugs, such as aspirin, streptomycin, phenobarbital, sulfonamides, nalidixic acid, and nitrofurantoin have been shown to increase renal clearance in alkaline urine (61). The possible effects of urine pH on the renal excretion of drugs has been illustrated by the observation that if urine is rendered sufficiently alkaline, the excretion of amphetamine is markedly delayed and effective blood levels, after a single dose, can be maintained for several days (62). 

Renal clearance of drugs is delayed in newborns and young infants, necessitating dose reductions (Figure 23.7), but after 8 to 12 months of age, renal excretion of drugs is comparable with that of older children and may even exceed that of adults. In young... 

Prescott LF. Mechanisms of renal excretion of drugs (with special reference to drugs used by anaesthetists). Br J Anaesth 1972 44(3) 246-51. 

John EG Guignard JP. Development of renal excretion of drugs during ontogeny. In Neonatal and fetal medicine. Polin RA FowWW Eds. Saunders WB, Philadelphia, pp 188-193,1997. 

Besseghir K, Roch-Ramel E. Renal excretion of drugs and other xenobiotics. Renal Physiol 1987 10 221-241. 

FIGURE 31.6 Schematic representation of the renal excretion of drugs. 

Saito H. [Molecular and cell biological analyses for intestinal absorption and renal excretion of drugs]. Yakugaku Zasshi 1997 Aug 117(8) 522-541. Japanese. 

C. A. Van Ginneken and F. G. Russel, Saturable pharmacokinetics in the renal excretion of drugs. Clin Pharmacokinet 16 38-54 (1989). 

Fig. 30.4 Schematic representation of (A) a nephron and (B) the renal excretion of drugs.

Increasing the urinary volume (diuresis) also increases the renal excretion of drugs that are extensively reabsorbed indeed, the concentration gradient bet,ween tubular fluid and plasma is decreased by the increased tubular water load. 

In addition, a number of transporters expressed on the basal and apical sides of the proximal and distal tubules are responsible for tubular secretion (Fig. 6.8) (Kusuhara and Sugiyama, 2009) thus, it is necessary to determine the relative contribution of each transporter to elucidate the mechanism for the renal excretion of drugs. For this purpose, an uptake assay using kidney slices and cultured cells transfected with complementary deoxyribonucleic acid (cDNA) of transporters can be conducted (Hasegawa et al., 2003). 

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