Drug elimination tubular reabsorption

Answer E. Back to basic principles. Zero-order elimination means that plasma levels of a drug decrease linearly with time. This occurs with ASA at toxic doses, with phenytoin at high therapeutic doses, and with ethanol at all doses. Enzymes that metabolize ASA are saturated at high plasma levels —> constant rate of metabolism = zero-order kinetics. Remember that application of the Henderson-Hasselbalch principle can be important in drug overdose situations. In the case of aspirin, a weak acid, urinary alkalinization favors ionization of the drug —>4 tubular reabsorption —>T renal elimination. 

The glomerular filtration rate (GFR) in normal males is estimated to be 125mL/min, and the results of the example calculation suggest that the drug is cleared by GFR. If the RCR had been less than 125 mL/min, tubular reabsorption of the drug would have been suspected. If it had been greater than 125 mL/min, tubular secretion would have been involved in the drug elimination. 

Pregabalin is eliminated from the systemic circulation primarily by renal excretion as unchanged drug, with a mean elimination half-life of 6.3 hours in subjects with normal renal function. Mean renal clearance was estimated to be 67 to 80.9 mL/min in young healthy subjects. Because pregabalin is not bound to plasma proteins, this clearance rate indicates that renal tubular reabsorption is involved. Pregabalin elimination is nearly proportional to Ccr. 

In congestive heart failure the drug elimination is retarded due to decreased perfusion and congestion of liver, also reduced glomerular filtration and increased tubular reabsorption. 

Small molecules are eliminated from the body largely by means of drug metabolism enzymes in the liver and other tissues and by urinary excretion. Large molecules are also eliminated by renal and hepatic mechanisms. Proteins that are less than 40 to 50 kDa are cleared by renal filtration with little or no tubular reabsorption. Larger proteins are less likely to be filtered but may be subject to phagocytosis in hepa-tocytes and Kupfer cells in the liver. Protein biotransformation—denaturation, proteolysis, and oxidative metabolism—is also important. 

Drugs affecting fiver enzymes may alter phenobarbital metabolism, but phenobarbital clearance is not affected by fiver blood flow. The elimination of phenobarbital is linear. Because tubular reabsorption of phenobarbital is pH dependent, the amount excreted renally can be increased by giving diuretics and urinary alkalinizers." ... 

Whereas filtration and secretion systems in the kidney serve to eliminate drug from the blood into the urine, tubular reabsorption serves to counteract excretion from the blood. Active reabsorption occurs via the proximal... 

Drugs which are either water-soluble or get metabolized gradually are mostly eliminated through the kidneys by the aid of these three essential phenomena, viz seeretion, glomerular filtration and tubular reabsorption. For instance, probenecid considerably retards tubular seeretion of penicillin thereby enhaneing its duration of action appreciably. 

The drug is not metabolized but is eliminated via the kidneys. Lisinopril probably undergoes glomerula filtration, tubular secretion and tubular reabsorption (42). 

It is, therefore, clear that a drug eliminated in urine may undergo one, all or any combination of the processes of glomerular filtration, tubular secretion or reabsorption. However, these mechanisms usually produce the net effect of removing a constant fraction of a drug presented to the kidneys through renal arterial blood. 

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