PRINCIPLES OF DRUG ADMINISTRATION IN RENAL-INSUFFICIENCY

Normal renal function is important for the excretion and metabolism of many drugs. Renal diseases which affect glomerular blood flow and fil tration, tubular secretion, reabsorption and renal parenchymal mass al ter drug clearances and lead to the need for alterations in dosage reg imens to optimise therapeutic outcome and minimise the risk of toxicit y. Renal disease is increasing and the cost of care has risen progress ively over the past decade, Part of these tests is related to inapprop riate drug therapy and excessive drug use. Although there are a variet y of methods for evaluating the various aspects of renal function, the most practical mid commonly used clinical measure of renal function i s estimated creatinine clearance (CL(CR)) as a marker for glomerular f iltration. This is useful since alterations in drug clearance are prop ortional to alterations in CL(CR) and this relationship is used as the basis for changing doses and dosage intervals for drugs which are lar gely renally excreted. Two populations, neonates and the elderly, are at risk of inappropriate drug dosage due to physiological changes in r enal function. Estimated CL(CR) may not be the best method of evaluati ng renal function in these patients, and dosage regimens should be car efully considered. Renal insufficiency and concurrent drug therapy use d in these populations can either increase or decrease drug absorption , depending on the particular agent. Drug distribution may be altered in renal insufficiency due to pH-dependent protein binding and reduced protein (primarily albumin) levels. Interestingly, renal disease may affect hepatic as well as renal drug metabolism; the exact mechanisms for these changes are not well understood. The most important quantita tive pharmacokinetic change is excretion. Glomerular filtration and tu bular process may both be affected but not to the same extent, and the type of renal disease may differentially affect filtration and excret ion. Drug removal by dialysis is dependent on a number of factors, inc luding the characteristics of a particular drug and the type of dialys is and equipment used. Therapeutic outcomes may be evaluated using end -points such as plasma concentrations, patient outcomes such as reduct ion in fever or negative cultures, and system-wide changes such as dru g-use or laboratory-use patterns.