Pharmacokinetics Flashcards
What is pharmacokinetics (PK), and what does it describe?
PK describes how drug concentrations change over time in the body due to absorption, distribution, metabolism, and excretion (ADME).
Why is blood commonly used to study pharmacokinetics?
Blood is easily accessible, and unbound drug concentrations in blood correlate with those in target tissues.
How does the unbound drug concentration in blood relate to the therapeutic target?
The unbound concentration in blood determines how much drug reaches the target site and binds to its receptor, influencing therapeutic effects.
What are the main goals of studying PK in drug discovery?
To predict drug efficacy, safety, dosing, and bioavailability.
How can PK parameters help predict drug efficacy?
PK parameters help determine drug concentration thresholds required for therapeutic effects.
What is the role of PK in lead optimization?
PK data guide structural modifications to improve drug performance, such as increasing bioavailability or reducing clearance.
How can PK data be used to predict drug toxicity?
PK helps determine how long a drug stays in the body and at what concentration it might cause toxicity.
What is the relationship between PK and pharmacodynamics (PD)?
PK describes how the drug concentration changes over time, while PD describes how the drug’s effects change over time.
What is the main difference between intravenous (IV) and oral (PO) drug administration in terms of drug concentration over time?
IV administration leads to an immediate and higher peak drug concentration, while oral administration involves absorption delays and first-pass metabolism.
Define the distribution phase and elimination phase in IV dosing.
The distribution phase is when the drug moves from the blood to tissues. The elimination phase is when the drug is metabolized and excreted.
Why does oral drug administration typically result in a lower peak concentration compared to IV administration?
Oral drugs must dissolve, be absorbed, and pass through first-pass metabolism before reaching systemic circulation, delaying and reducing peak concentration.
What is first-pass metabolism, and how does it affect oral bioavailability?
First-pass metabolism occurs when a drug is metabolized in the liver and gut wall before reaching systemic circulation, reducing bioavailability.
What is the significance of the area under the curve (AUC) in PK analysis?
AUC represents total drug exposure over time and helps compare drug bioavailability and clearance.
How does subcutaneous (SC) or intramuscular (IM) administration differ from IV and PO administration in terms of absorption and metabolism?
SC and IM administration bypass first-pass metabolism but have slower absorption rates than IV due to tissue permeability differences.
What does volume of distribution (Vd) represent?
Vd represents how widely a drug distributes in body tissues relative to blood plasma.
How do lipophilicity and plasma protein binding affect Vd?
Lipophilic drugs with low plasma protein binding have a high Vd, while hydrophilic drugs or those highly bound to plasma proteins have a low Vd.
What are the differences between low, moderate, and high Vd drugs?
Low Vd: Drug remains mostly in plasma. Moderate Vd: Drug distributes evenly between blood and tissues. High Vd: Drug accumulates in tissues rather than plasma.
How can Vd be used to determine the loading dose of a drug?
The loading dose is calculated as Loading Dose = Vd × Target Plasma Concentration to quickly achieve therapeutic levels.
Why does a high Vd not always indicate high unbound drug concentration in target tissues?
High Vd may indicate extensive tissue binding, but it does not guarantee a high concentration of the free drug at the target site.
What does the AUC represent in a concentration vs. time graph?
AUC represents the total drug exposure over time.
How can AUC be used to compare drug exposure between different compounds?
AUC helps compare how much drug reaches systemic circulation and is used to assess bioavailability.
What factors influence the AUC of a drug?
Dose, clearance rate, metabolism, and bioavailability.
What is clearance (CL), and how is it measured?
CL is the rate at which a drug is removed from plasma, measured in volume per time (e.g., mL/min/kg).
What are the primary organs responsible for drug clearance?
The liver (hepatic clearance) and kidneys (renal clearance).
