Renal drug excretion

Elimination J. Renal blood flow i GFR i ARTS J. No. functioning nephrons T ty2 renally excreted drugs... 

In hepatorenal syndrome (HRS), which is an acute episode, the clearance of renally excreted drugs and metabolites (pravastatin, simvastatin, rosu-vastatin, acipimox, fibrates) may be reduced. During an episode of HRS, anti-hyperlipidaemic medication should be withheld. 

Knowledge of the extraction ratio of a particular compound allows the preceding to be simplified into more practical terms. Renal excretion drug interactions resulting from transport inhibition cause reductions in A particularly useful parameter for elucidating mechanisms of renal excretion is excretion ratio (XR). XRis simply renal clearance corrected for filtration clearance... 

Drugs can be cleared from the body by metabolism as well as renal excretion, and when this occurs it is not possible to measure directly the amount cleared by metabolism. However, the total clearance rate (TCR), or total body clearance, of the drug can be calculated from its pharmacokinetic parameters using the following equation ... 

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],... 

The majority of evidence supporting the pH-partition hypothesis is from studies of gastrointestinal absorption, renal excretion, and gastric secretion of drugs [11]. While correlation between absorption rate and pKa was found to be consistent with the pH-partition hypothesis, deviations from this hypothesis were often reported [12]. Such deviations were explained by the existence of a mucosal unstirred layer [13,14] and/or a microclimate pH [15]. 

Although the pharmacokinetics of rifaximin in patients with renal insufficiency has not been specifically studied, its very low renal excretion makes any dose adjustment unnecessary. The same holds true for patients with hepatic insufficiency. In fact, the mean peak drug plasma concentrations (i.e. 13.5 ng/ml) detected in subjects with hepatic encephalopathy patients given rifaximin 800 mg 3 times daily for 7 days [34, 108] were not dissimilar to those found in healthy subjects [102] and patients with IBD [98], Indeed, in all the trials performed in this condition the drug has been well tolerated [33, 77],... 

It is eliminated primarily by renal excretion as unchanged drug dosage adjustment is required in patients with renal dysfunction. 

Hypomagnesemia is usually associated with disorders of the intestinal tract or kidneys. Drugs (e.g., aminoglycosides, amphotericin B, cyclosporine, diuretics, digitalis, cisplatin) or conditions that interfere with intestinal absorption or increase renal excretion of magnesium can cause hypomagnesemia. 

Peak plasma levels are reached about 1.5 h after oral ingestion, the maximum concentrations being in the order of 2 - 3 ng equivalents/ml (parent drug + metabolites) for an oral 1 mg dose. The elimination from the plasma is biphasic and proceeds with mean half-lives of 6 h (a-phase) and 50 h ((3-phase). Similar elimination half-lives are obtained from the urinary excretion. The cumulative renal excretion is practically the same after oral and intravenous administration and amounts to 6 - 7 % of the radioactivity dosed. The main portion of the dose, either oral or intravenous, is eliminated by the biliary route into the faeces. The kinetics of bromocriptine has been demonstrated to be linear in the oral dose range from 2.5 to 7.5 mg. 

The elimination half life of a drug will thus increase if the volume of distribution is increased as for lipophilic drugs in the elderly or if the clearance is affected, the latter mainly hepatic metabolism or renal excretion. 

Figure 15.2 Transport proteins involved in the intestinal absorption and the renal and hepatic excretion of drugs. In the intestine, drugs are taken up from the luminal side into enterocytes before the subsequent elimination into blood. In hepatocytes, drugs are taken up from the blood over the basolateral membrane and excreted over the canalicular membrane into bile. In the renal epithelium, drugs undergo secretion (drugs are taken up from the blood and excreted into the urine) or reabsorption (drugs are taken up from the urine and are excreted back into blood). Uptake transporters belonging to the SLC transporter superfamily are shown in red and export pumps...

Biotransformation involves the chemical alteration of a molecule to alter its effects. This often terminates the pharmacological effects of a drug, but active metabolites are produced in some cases. Biotransformation also changes the ease with which a drug is eliminated. This involves conversion of the drug to a more hydrophilic metabolite that enhances renal excretion. Although this process pertains to most drugs, it probably... 

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