Relationships Among PK Variables Under Linear Kinetics
Under linear kinetics, concentration, AUC, and elimination rate are directly proportional to this.
What is the dose?
If active transport is NOT involved, distribution equilibrium is achieved when this specific concentration is equal on both sides of a membrane (Cu=Cu,T).
What is the free (or unbound) drug concentration?
This parameter is defined as the proportionality constant relating the excretion rate of unchanged drug in urine to the plasma concentration of the drug.
What is renal clearance (CLr)?
While the rate of absorption is described by ka and tmax, the extent of absorption is described by AUC and this parameter.
What is bioavailability (F)?
his type of kinetic order means a constant amount of drug is being processed per unit of time.
What is zero-order kinetics?
Volume of distribution (V) has an inverse relationship with Cmax, no relationship with AUC, and a direct relationship with this time-based parameter.
What is tmax?
According to the physiological representation of V.
V has a direct relationship with the fraction unbound in plasma (fu) and an inverse relationship with this fraction.
What is the fraction unbound in tissue (fu,T)?
For a high ER drug, its hepatic clearance (CLh) approximates this physiological rate.
What is the hepatic blood flow rate (Qh)?
For most drugs, taking a dose with food increases the gastric emptying time, which prolongs tmax but generally has no effect on this.
What is the extent of absorption (or F)?
In the Michaelis-Menten equation, this parameter represents the enzyme efficiency and the maximum rate of metabolism.
What is Vmax?
A patient is admitted to the hospital and started on a continuous IV infusion of a medication at a rate (R0) of 50 mg/h. If the patient's total clearance (CL) for this drug is 5 L/h, this will be their steady-state concentration (Css).
What is 10 mg/L?
A decrease in plasma protein binding results in a temporary increase in Volume of Distribution (V) and this other primary PK parameter, which keeps t1/2 unchanged.
What is total clearance (CL)?
A patient has a normal Glomerular Filtration Rate (GFR) of 100 mL/min. If they are taking a drug that is 80% bound to plasma proteins, the filtration clearance (CLf) for this specific drug is this value.
What is 20 mL/min?
This type of kinetics is defined as absorption rate-limited elimination, characterized by ka being much smaller than k
What is flip-flop kinetics?
In the presence of a noncompetitive inhibitor, Vmax decreases while this parameter, which represents the enzyme's binding affinity for a drug, remains exactly the same.
What is Km?
A patient has severe edema, doubling their volume of distribution (V) for a hydrophilic drug, but their clearance (CL) remains normal. This will result in this specific proportional change to the drug's elimination half-life.
What is a doubling (or twofold increase)?
A critically ill patient experiences a decrease in muscle mass, leading to a decrease in tissue protein binding of a drug. Under linear distribution equilibrium, this will lead to this directional change in the total Volume of Distribution (V).
What is a decrease?
A large, polar drug molecule is given to a patient with a biliary obstruction, decreasing the excretion rate of the unchanged drug in the bile. If this is a high extraction ratio (ER) drug, this obstruction will have this specific effect on the hepatic clearance (CLh).
What is no effect?
An extended-release capsule is designed to exhibit flip-flop kinetics to prolong dosing intervals. In this specific scenario, the amount of drug remaining to be absorbed is directly proportional to this.
What is the drug amount in the body (or drug concentration in plasma)?
A patient on a low extraction ratio (ER) drug develops hypoalbuminemia, causing their fraction unbound (fu) to increase. Assuming linear PK principles for a low ER drug, this change will have an inverse effect on this specific concentration parameter.
What is total steady-state concentration (Css)?
Two patients receive the same continuous IV infusion rate (R0) of a drug. Patient A has double the volume of distribution (V) of Patient B, but their clearances (CL) are identical. What is the difference in their steady-state concentrations (Css).
What is no difference (they are exactly the same)?
A patient taking highly protein-bound Phenytoin is started on Valproic Acid, which displaces Phenytoin from albumin. After reaching a new distribution equilibrium, the free fraction (fu) in plasma has increased, resulting in this specific change to the bound concentration in the tissue (Cb,T)
What is an increase?
A patient receives a 100 mg IV dose of a drug with a total clearance of 5 L/h. If 40 mg of the unchanged drug is eventually recovered in their urine, their renal clearance (CLr) is exactly this value.
What is 2 L/h?
A patient takes an oral drug where 100% dissolves and permeates the gut wall, and the liver is the only site of metabolism. If the patient's hepatic extraction ratio (ER) for this drug is 0.4, the absolute oral bioavailability (F) will be this exact percentage.
What is 60% ?
A patient receives a high extraction ratio (ER) drug intravenously. If the patient goes into shock and their hepatic blood flow (Qh) drops significantly, this physiological change will have an inverse effect on this time-based pharmacokinetic parameter.
What is the elimination half-life (t1/2)?