Which groups exhibit decreased plasma protein binding of drugs and inefficient hepatic metabolism compared with adults?

Which groups exhibit decreased plasma protein binding of drugs and inefficient hepatic metabolism compared with adults?

• A. Only neonates
• B. Only geriatrics
• C. Both neonates and geriatrics
• D. Adults

Answer: (C)

The concept here is how age affects pharmacokinetics, specifically protein binding and hepatic metabolism. In neonates, albumin levels are low and bilirubin and other endogenous compounds can compete for binding sites, so a larger fraction of drugs remains unbound in the plasma. At the same time, the liver is immature and many drug-metabolizing enzymes (like certain cytochrome P450 enzymes and conjugation pathways) have not reached adult activity, so hepatic metabolism is slower. The combination of more free drug and slower clearance increases the potential for drug effect and toxicity. In the elderly, there is often a reduction in hepatic mass and hepatic blood flow, along with a decline in several drug‑metabolizing enzymes. This slows metabolism and clearance. Albumin levels tend to fall with age as well, which can increase the free fraction of acidic drugs, further altering pharmacodynamics. Together, these changes mean that, compared with healthy adults, both neonates and older adults typically exhibit decreased plasma protein binding and less efficient hepatic metabolism, leading to longer drug effects and a higher risk of toxicity if dosing isn’t adjusted.

The concept here is how age affects pharmacokinetics, specifically protein binding and hepatic metabolism. In neonates, albumin levels are low and bilirubin and other endogenous compounds can compete for binding sites, so a larger fraction of drugs remains unbound in the plasma. At the same time, the liver is immature and many drug-metabolizing enzymes (like certain cytochrome P450 enzymes and conjugation pathways) have not reached adult activity, so hepatic metabolism is slower. The combination of more free drug and slower clearance increases the potential for drug effect and toxicity.

In the elderly, there is often a reduction in hepatic mass and hepatic blood flow, along with a decline in several drug‑metabolizing enzymes. This slows metabolism and clearance. Albumin levels tend to fall with age as well, which can increase the free fraction of acidic drugs, further altering pharmacodynamics. Together, these changes mean that, compared with healthy adults, both neonates and older adults typically exhibit decreased plasma protein binding and less efficient hepatic metabolism, leading to longer drug effects and a higher risk of toxicity if dosing isn’t adjusted.