Mechanisms of Renal Excretion of Drugs (With Special Reference to Drugs Used by Anaesthetists)

Abstract

Contrary to popular belief, the elimination of active drug by renal excretion is a relatively unimportant mechanism for the termination of drug action. Most drugs are weak electrolytes which are lipid-soluble in the un-ionized state, and as such they cannot be excreted by the kidney because they are extensively reabsorbed. These lipid-soluble drugs are invariably metabolized to more water-soluble derivatives which usually have little or no pharmacological activity and can readily be excreted in the urine. The duration of action is therefore determined largely by redistribution, metabolism, and in the case of the anaesthetic gases, by elimination through the lungs. On the other hand, some drugs have limited lipid solubility or are highly ionized in the physiological range of pH. They tend to be eliminated largely unchanged by renal excretion and their duration of action may be prolonged in the presence of impaired renal function. Familiar drugs which fall into this category include quaternary ammonium bases, ganglion blocking drugs, non-depolarizing muscle relaxants, many antibiotics, thiazide diuretics, methotrexate, digoxin and barbitone (table I). From a practical point of view it is obviously important to know whether the major route of elimination of a drug is through metabolism or renal excretion. TABLE I. Some drugs jor which renal excretion is normally an important route of elimination.

A Systematic Review of Gastric Acid-Reducing Agent-Mediated Drug–Drug Interactions with Orally Administered Medications

“…In alkaline urine, the renal clearance of weakly acidic drug molecules will tend to be increased. In an alkaline environment, weakly acidic drugs are polar (charged), and thus are less likely to pass through membranes for reabsorption into the systemic circulation, and weakly basic drugs will be rendered neutral and remain non-polar (uncharged), allowing them to be more likely to pass through membranes to re-enter the systemic circulation and increase their systemic exposure [32]. Increased urinary pH may lead to either toxic concentrations being reached for weakly basic drug molecules or reduced efficacy for weakly acidic drug molecules.…”

“…Since antacids are basic compounds, they have the potential to alkalize urine, altering the renal excretion of weakly acidic and weakly basic medications [32]. Possible mitigation strategies proposed in the prescribing information include selection of an alternative ARA (H2RA or PPI), monitoring for increased or decreased effects of substrate medication, and possible dose adjustment of the substrate medication.…”

Clinical Pharmacokinetics of Muscle Relaxants

“…These same elimination criteria most likely apply in humans as well, since 5 patients with renal failure showed significant prolongation of blockade during abdominal surgery under gallamine-aided anaesthesia (Churchill-Davidson et aI., 1967). Numerous other reports describe prolongation of blockade following use of gallamine in patients with renal failure (see Prescott, 1972).…”

Development of a Microfluidic System Comprising Dialysis and Secretion Components for a Bioassay of Renal Clearance

“…1 Excretion consists of three processes: glomerular filtration in a renal corpuscle, tubular secretion, and reabsorption in a renal tubule. [2][3][4] Glomerular filtration is a size-dependent separation process by which small drugs are excreted by ultrafiltration, whereas macromolecular drugs and drugs strongly bound to plasma proteins are not. Tubular secretion is mediated by several kinds of transporters, including P-glycoprotein (P-gp).…”