Drug dosage in renal failure

Bennett WM. Guide to drug dosage in renal failure. In Speight TM, Elolford N, eds. Avery s drug treatment, 4th edn. Auckland ADIS International 1997 1725-92. 

Nafcillin is primarily cleared by biliary excretion. Oxacillin, dicloxacillin, and cloxacillin are eliminated by both the kidney and biliary excretion no dosage adjustment is required for these drugs in renal failure. Because clearance of penicillins is less efficient in the newborn, doses adjusted for weight alone result in higher systemic concentrations for longer periods than in the adult. 

Tetracyclines are excreted mainly in bile and urine. Concentrations in bile exceed those in serum tenfold. Some of the drug excreted in bile is reabsorbed from the intestine (enterohepatic circulation) and may contribute to maintenance of serum levels. Ten to 50 percent of various tetracyclines is excreted into the urine, mainly by glomerular filtration. Ten to 40 percent of the drug is excreted in feces. Doxycycline and tigecycline, in contrast to other tetracyclines, are eliminated by nonrenal mechanisms, do not accumulate significantly and require no dosage adjustment in renal failure. 

Skin heavily infected with M leprae may contain several times as much of the drug as normal skin. Sulfones are excreted into bile and reabsorbed in the intestine. Excretion into urine is variable, and most excreted drug is acetylated. In renal failure, the dose may have to be adjusted. The usual adult dosage in leprosy is 100 mg daily. For children, the dose is proportionately less depending on weight. 

Pharmacokinetics Slow intravenous infusion is employed for treatment of systemic infections or for prophylaxis. Because vancomycin is not absorbed after oral administration, this route is only employed for the treatment of antibiotic-induced colitis due to Q difficile. Inflammation allows penetration into the meninges. Metabolism is minimal 90-100 % is excreted by glomerular filtration. [Note Dosage must be adjusted in renal failure since the drug will accumulate. Normal half-life is 6-10 hours compared to over 200 hours in end-stage renal disease.]... 

Renal dysfunction reduces the clearance of tolrestat, with corresponding increases in the half-life. No effect was reported on the volume of distribution or absorption, suggesting that the dose should be reduced in renal failure (Troy et al., 1992). The fact that one-third of the dose is eliminated by the liver makes it possible to use the drug even in both liver and kidney dysfunction if the possible doubling in the plasma levels is compensated by a reduction in the dosage. 

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