Drug Elimination: Excretion

: loss of drug by excretion (primarily in kidneys; unchanged species) and/or metabolism (primarily in liver; different chemical). The process is irreversible

is defined as: The proportionality factor that relates the renal elimination rate of a drug with the drug concentration in blood (plasma). Volume of fluid (blood, plasma) that is completely cleared of drug by the kindeys per unit time. The units for clearance are volume/time (for example: mL/min, L/h) Example: ClRenal = 100 mL /min 100 mL of plasma (blood) are cleared of drug every minute

the fraction of a drug passing by the kidney which is eliminated by the kidney and normally excreted in urine. The value of an extraction ratio for a drug and eliminating organ can range from: 0 the drug is not eliminated as in this case: Centering = Cleaving 1 all the drug is eliminated as in this case: Cleaving = 0 Link of Renal rxtraction ratio to Renal Clearance

Drug enters the kidney via the renal artery and leaves partly in the exiting renal vein and partly in urine. Urinary excretion (4) is the net effect of glomerular filtration of unbound drug (1) and tubular secretion (2), processes adding drug into the proximal part of the lumen of the tubule, and tubular reabsorption (3) of drug from the lumen and collecting tubule back into the perfusing blood.

(occurs always) Approximately 1.2L of blood per minute goes to the kidneys Of this volume, about 10% (120 mL/min) is filtered at the glomerulus by the hydraulic pressure exerted by the arterial blood As a general rule, only unbound drug in plasma water is filtered; protein-bound drug is too large to pass through the fenestration of the glomerulus Creatinine (endogenous compound) is neither bound to plasma proteins nor significantly excreted. The entire filtered load is excreted in urine. Its renal clearance is a measure of the glomerular filtration rate (GFR)

Active transport (carrier-mediated) from blood to lumen of nephron. Predominant in the proximal tubule Transporter systems lack a high degree of specificity (variety of substances are transported by them) Drug interactions Saturation

Occurs all along the nephron For most drugs, reabsorption occurs by passive diffusion. Drug properties important (lipoidal membranes of the cells that form the tubule act as barrier to water-soluble and ionised substances) Lipophilic molecules tend to be extensively reabsorbed, whereas polar molecules (eg conjugates) do not The extensive reabsorption of water is the driving force for solutes (including drugs) passive re-absorption. Active reabsorption also occurs

Increases ClR- If a drug is only eliminated by filtration fu = 1 (not bound to proteins) Clfiltration = ClCR fu < 1 (bound to proteins) Clfiltration = ClCR x fu Clrenal, drug = Clfiltration Increases ClR-If a drug is eliminated by filtration and secretion ClR= Clfiltration+Clsecretion ClR=(ClCRxfu)+Clsecretion Clrenal, drug > Clfiltration Decreases ClR-If a drug is eliminated by filtration and it is reabsorbed ClR= Clfiltration-Clreabsorption ClR=(ClCRxfu)-Clreabsorption Clrenal, drug < Clfiltration