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Pharmacokinetics Fundamentals
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Question
What is the definition of bioavailability (F) in pharmacokinetics?
Answer
Bioavailability (F) is the fraction of an administered dose that reaches the systemic circulation in an unchanged form.
Question
How does first-pass metabolism affect the oral bioavailability of a drug?
Answer
First-pass metabolism in the intestinal wall and/or liver metabolizes drug before it reaches systemic circulation, thereby reducing the oral bioavailability.
Question
What is the relationship between clearance (CL), volume of distribution (Vd), and the elimination rate constant (ke)?
Answer
Clearance (CL) is related to volume of distribution and the elimination rate constant by the formula $CL = k_e \times V_d$, where $k_e$ is the elimination rate constant and $V_d$ is the volume of distribution.
Question
What is the formula for a drug's elimination half-life in terms of the elimination rate constant?
Answer
The elimination half-life is given by $t_{1/2} = \dfrac{0.693}{k_e}$, where $k_e$ is the elimination rate constant.
Question
How do you calculate the loading dose required to reach a target plasma concentration?
Answer
The loading dose is calculated as $\text{Loading dose} = \dfrac{C_{target} \times V_d}{F}$, where $C_{target}$ is the desired plasma concentration, $V_d$ is the volume of distribution, and $F$ is bioavailability (use $F=1$ for IV administration).
Question
What formula gives the maintenance dose rate required to maintain a steady-state concentration?
Answer
The maintenance infusion rate to maintain steady-state concentration is $\text{Rate}_{in} = C_{ss} \times CL$. For intermittent dosing, the maintenance dose per interval is $\text{Dose}_{\tau} = \dfrac{C_{ss} \times CL \times \tau}{F}$, where $C_{ss}$ is steady-state concentration, $CL$ is clearance, $\tau$ is the dosing interval, and $F$ is bioavailability.
Question
Given $V_d = 50\,\text{L}$, $CL = 5\,\text{L/hr}$, and desired $C_{ss} = 2\,\text{mg/L}$, what is the maintenance infusion rate?
Answer
Use $\text{Rate}_{in} = C_{ss} \times CL$. Thus $\text{Rate}_{in} = 2\,\text{mg/L} \times 5\,\text{L/hr} = 10\,\text{mg/hr}$.