Pharmacokinetics Key Parameters

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Questions and Answers

What does bioavailability measure?

The percentage of a drug that causes side effects.

The time it takes for a drug to be eliminated from the body.

The fraction of the administered dose that reaches systemic circulation. (correct)

The effectiveness of a drug in treating a specific condition.

Which of the following parameters are used to evaluate bioavailability?

Therapeutic index, absorption rate, and distribution half-life.

Rate of elimination, volume of distribution (Vd), and clearance (Cl).

Area under the serum concentration/time curve (AUC), maximum concentration (Cmax), and time to maximum concentration (Tmax). (correct)

Dosing frequency, peak plasma concentration, and average steady-state concentration.

How is bioavailability (F) calculated when comparing extravascular and intravenous doses?

F = (AUCPO/AUCIV)(DPO/DIV) (correct)

F = AUCPO / AUCIV while accounting for patient metabolism.

F = AUCIV / AUCPO

F = AUCPO - AUCIV divided by the volume of distribution.

What is required for a generic drug to be considered bioequivalent to a branded drug?

It must produce a similar serum concentration/time profile to the branded drug. Signup and view all the answers

What happens to a portion of an orally administered drug that does not dissolve?

It is eliminated in the stool. Signup and view all the answers

What happens to the free fraction of a drug when a second, highly protein-bound drug is administered concurrently?

It increases due to displacement. Signup and view all the answers

If a drug is present in a total of 3 g and results in a concentration of 0.15 g/L, what is the volume of the tank?

30 L Signup and view all the answers

How is the volume of distribution calculated when a drug is administered intravenously?

By dividing the plasma concentration by the administered dose. Signup and view all the answers

What loading dose should be recommended for achieving a drug level of 2 μg/mL given a volume of distribution of 10 L?

20 mg Signup and view all the answers

What effect does the elimination rate constant have on drug dosing if administered at a rate of 2 mg/hr?

It predicts the time for the drug to reach steady state. Signup and view all the answers

Why is protein binding important in pharmacokinetics?

It determines the amount of drug that is free and active. Signup and view all the answers

Which of the following statements about volume of distribution is true?

It helps to determine how extensively a drug distributes in body tissues. Signup and view all the answers

What is the formula for hepatic clearance?

ClH = LBF x ERH Signup and view all the answers

Which factor does not influence hepatic clearance?

Renal blood flow Signup and view all the answers

Which statement is true concerning the clearance of a drug?

Cl = ClH + ClR represents total clearance. Signup and view all the answers

What does intrinsic clearance (Cl'int) specifically represent?

The inherent ability of the enzyme to metabolize the drug Signup and view all the answers

Which of the following contributes to an increase in hepatic clearance (ClH)?

An increase in liver blood flow Signup and view all the answers

What do Vmax and Km represent in the context of drug metabolism?

Vmax is the maximum rate of drug metabolism, and Km is the concentration at which half-maximal rate occurs. Signup and view all the answers

Which of the following formulas represents renal clearance?

ClR = RBF x ERR Signup and view all the answers

What factor is represented by 'fB' in the formula for hepatic clearance?

The unbound drug concentration in the bloodstream Signup and view all the answers

How does an increase in the renal excretion ratio (ERR) affect renal clearance (ClR)?

It increases renal clearance. Signup and view all the answers

What is the primary reason clearance is considered the most important pharmacokinetic parameter?

It determines the maintenance dose required for steady-state serum concentration. Signup and view all the answers

Which organ is primarily responsible for the Phase I metabolic reactions?

Liver Signup and view all the answers

What does the extraction ratio (ER) measure?

The ability of an organ to remove or extract drug from the blood. Signup and view all the answers

Which enzyme system is primarily responsible for Phase I drug metabolism?

Cytochrome P-450 (CYP) enzyme system Signup and view all the answers

How is the maintenance dose (MD) expressed in pharmacology?

mg/h or µg/min Signup and view all the answers

Which of the following is involved in Phase II reactions of drug metabolism?

Formation of glucuronide or sulfate esters Signup and view all the answers

What is the formula for calculating clearance (Cl) based on organ function?

Cl = Blood flow x Extraction ratio (ER) Signup and view all the answers

What happens to the metabolite generated in Phase I reactions?

It is made more water-soluble for easier elimination. Signup and view all the answers

Which of the following best describes the function of the kidney in drug elimination?

It filters and secretes drugs through the nephron. Signup and view all the answers

Study Notes

Pharmacokinetics Parameters

Pharmacokinetics (PK) is the study of how drugs enter, travel through, and leave the body.
Key PK parameters include bioavailability, volume of distribution, clearance, and half-life.
Bioavailability: Fraction of administered dose reaching systemic circulation. Affected by drug administration route, rate of absorption, and presystemic metabolism.
Volume of distribution (Vd): Theoretical volume in which a drug could distribute if evenly dispersed. A larger Vd implies a greater drug distribution into tissues beyond the bloodstream.
Clearance (Cl): Volume of plasma that is completely cleared of drug per unit time. High clearance often suggests rapid elimination.
Half-life (t1/2): Time for drug concentration to decrease by half. Shorter half-life indicates faster elimination.

Bioavailability

Bioavailability (F) is the fraction of a drug that reaches the systemic circulation after administration.
Expressed in percentages (%).
Measured using AUC (area under the curve) from extravascular and intravenous administration after the same dose.
Determined by absorption, distribution, and metabolism.
Drug absorption process is a critical factor determining bioavailability.
Oral bioavailability is affected by factors such as solubility, stability, and GI transit time.

Absorption

Absorption is the process where a drug moves from the site of administration into the bloodstream.
The drug must cross biological membranes before entering the vascular system.
Factors influencing absorption include route of administration, drug solubility, and the presence of transport mechanisms.

Bioequivalence

Bioequivalence assessment is necessary for generic drugs.
Determining serum concentration/time profiles for generic and original drugs under similar conditions.
Bioequivalents need to have similar serum concentration/time profiles (AUC, Cmax, Tmax).
Generic medications match bioavailability, concentration, and timing of the absorption of the original drug.

Volume Distribution

Volume of distribution (Vd) is a theoretical value representing the apparent volume into which a drug distributes in the body.
Calculated using the initial drug amount and concentration,
Vd is not equal to the actual volume.
Factors influencing Vd include drug properties, plasma protein binding, and tissue binding.
It is essential to understand the relationship between physiological characteristics and drug distribution.

Metabolism and Elimination Clearance

Clearance (Cl) is the volume of plasma that is completely cleared of a drug per unit time.
Clearance describes the amount of drug cleared from the blood.
The rate of elimination can vary depending on the location of metabolic processes.
Factors influencing clearance include hepatic and renal blood flow and metabolic activity.

Half-Life and Elimination Rate Constant

Half-life (t1/2) is the time required for the drug concentration in the body to decrease by half.
Elimination rate constant (Ke): Fraction of drug removed from the body per unit time.
Clearance equals Ke multiplied by Volume of distribution.

Clinical Applications of Elimination Rate Constant and Half-life

Estimating steady state.
Predicting non-steady-state plasma levels following initiation of an infusion.
Predicting fluctuations in plasma concentration within a dosing interval.

Relationship Among Pharmacokinetic Parameter

Half-life is influenced by clearance and volume of distribution.
These are independent variables because one can vary without the other.

Exercise Problems

Several exercise problems on calculating bioavailability, clearance, volume of distribution, and half-life are given.
These allow for practical application of the concepts.

Michaelis-Menten Pharmacokinetics

Drug metabolism by enzymes; e.g., cytochrome P-450.
Non-linear pharmacokinetics.
Steady-state drug concentrations increase disproportionately with rising dosage.
Enzyme and drug reactions create concentration-dependant clearance.

Zero-Order Pharmacokinetics

Constant rate of metabolism regardless of concentration.
Clearance decreases when concentrations rise, eventually approaching saturable conditions.

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Description

Dive into the essential aspects of pharmacokinetics, including critical parameters such as bioavailability, volume of distribution, clearance, and half-life. This quiz will test your understanding of how these factors influence drug action and elimination in the body.