Drug Elimination and Clearance Concepts

A direct measure of drug elimination from the body, including plasma and highly perfused tissues.

Rate constant for elimination of a drug.

Pharmacokinetic method that determines clearance without compartments.

Area under the curve from time zero to infinity after drug administration (IV)

Average time a drug stays in the body.

Drug elimination rate matches the absorption rate, maintaining stable drug levels in the body.

Drug elimination and absorption that are consistent and maintain constant ratio regardless of dose.

Plasma and rapidly equilibrating tissues (like kidney and liver)

How much a weak acid breaks down into ions depends on the urine's pH. The effect is strongest when the drug's pKa is between 3 and 8.

A drug with a pKa of 5 will be more affected by urine pH changes than a drug with a pKa of 3. A drug with a pKa of 2 is mostly ionized regardless of urine pH.

The extent to which a weak base breaks down into ions is greatly influenced by urine pH, especially when the drug's pKa is between 7.5 and 10.5.

Drugs are eliminated by the kidneys through a combination of filtration, active secretion, and reabsorption.

This is a process where the kidneys actively pump drugs out of the bloodstream. It can be saturated, meaning it can only handle a limited amount of drug.

Reabsorption of weak acids and bases depends on urine pH and drug ionization.

Increased urine flow, caused by things like alcohol or caffeine, decreases drug reabsorption and increases excretion.

Using diuretics can increase the excretion of drugs by the kidneys.

The rate at which a drug is removed from the body by the kidneys, measured as the volume of plasma cleared of drug per unit time.

The rate at which a drug is removed from the body by mechanisms other than the kidneys (e.g., metabolism, excretion in bile).

The overall rate at which a drug is removed from the body, combining both renal and nonrenal clearance.

The proportion of the administered drug dose that is excreted unchanged in urine.

Formation of drug crystals in the renal tubules, potentially leading to kidney damage.

A way to model drug elimination using mathematical equations without needing exact information about kidney function, secretion, or reabsorption.

A marker for a patient's overall renal function, used by doctors to adjust drug dosages based on how well the kidneys are working.

When a drug is removed from the body only by filtering through the kidneys, without being reabsorbed back into the bloodstream.

The process where the kidneys filter waste products, including some drugs, from the blood.

A drug that is freely circulating in the bloodstream, not attached to proteins, which is more easily filtered by the kidneys.

The rate at which the kidneys remove a drug from the body. It's a measure of how efficiently the kidneys filter and eliminate the drug.

Clearance is determined by the slope of a curve plotting the rate of drug excretion in urine against plasma concentration. A steeper slope indicates faster excretion.

The total amount of drug excreted in urine over time. It can be related to the area under the concentration-time curve (AUC).

Renal clearance is a summation of three processes: filtration, secretion, and reabsorption. It represents the combined effect of these processes on a drug's elimination.

By plotting cumulative drug excretion against AUC, we can determine renal clearance from the slope of the resulting curve.

ClR is determined by measuring the slope and intercept of a graph plotting drug concentration in urine against creatinine clearance (CrCl).

Creatinine Clearance: A measure of kidney function that estimates the GFR. It reflects the rate at which creatinine is cleared from the blood.

Missing data points can make it challenging to accurately calculate cumulative excretion and therefore renal clearance.

The intercept in the ClR formula reflects the contribution of reabsorption and secretion to the overall clearance.

Using graphs to visualize and analyze the relationship between drug excretion and plasma concentration to determine renal clearance.

A steeper slope on a curve indicates a higher rate of drug excretion, meaning the drug is being eliminated from the body more quickly.

A shallower slope on a curve indicates a slower rate of drug excretion, meaning the drug is being eliminated from the body more slowly.

Renal clearance helps predict how long a drug will stay in the body and how efficiently it will be eliminated, influencing dosing strategies.