**Pharmacokinetics**- Pharmacokinetics describes
over time.*changes in plasma drug concentration*

- Pharmacokinetics describes
- Distribution and elimination
**Features of One-compartment model**- The drug appears to
**distribute instantaneously**after IV administration of a single dose. - If the mechanisms for drug elimination, such as biotransformation by hepatic enzymes and renal secretion, are not saturated following the therapeutic dose, a
*semilog*plot of**plasma concentration versus time**will be*linear.* - The slope of the semilog plot is –k ,where
**k is the rate constant of elimination**and has**units of time**, and the^{–1}**intercept on the y axis is C**_{0} - Drug elimination is
**first order**- a
of drug is*constant fraction***eliminated per unit time** - For example,
**one-half of the drug**is eliminated*every 4 hours* - With
**passage of every half**–life ,*50% of concentration*falls down *First order*is a**rapid way**of drug elimination than Zero order- Elimination of most drugs is a
**first-order process.**

- a
- The
**plasma drug concentration****(Ct) at any time (t)**after administration is given by**ln C**_{t}**=****ln C**_{0}**−****kt****log C**_{t}**=****log C**_{0}–kt/2.303

- The drug appears to

- relationship of the
**plasma concentrations****at any two points**in time is given by**ln C**_{2}**=****ln C**_{1}**−****k (t**_{2}**−****t**_{1})**log C**_{2}**=****log C**_{1}**−****k/2.303 (t**_{2}**−****t**_{1})

**CL****=****k****.****Vd****rate constant**of elimination = k**Volume of distribution**= Vd- whole body
**clearanc**e = CL

**Features of**Two-compartment model- The two-compartment model is a
for*more common model***distribution and elimination of drugs** **Distribution phase followed by Elimination phase**in the plasma concentration of a drug are observed because of a*Initial rapid changes***distribution phase**, the time required for the drug to reach an equilibrium distribution between a central compartment, such as the plasma space, and a second compartment, such as the aggregate tissues and fluids to which the drug distributes.- After distribution, a
**linear decrease**in the log drug concentration is observed if the elimination phase is*first order.* - The expressions
**for ln Ct and CL for a one-compartment model**also apply during the*elimination phase for drugs*that obey**a two-compartment model.**

- The two-compartment model is a
**First-order elimination**- It refers to the elimination of
**a constant fraction of drug per unit time** - the
is a*rate of elimination***linear function**of the*plasma drug concentration.* - Occurs when elimination systems are
*not saturated by the drug.*

- It refers to the elimination of
**Zero-order elimination**- occur when
**therapeutic doses of**drugs*exceed the capacity*of elimination mechanisms. - In this model, the
**plot of the log of the plasma concentration**versus**time**will be*concave upward* - a
**constant amount of drug**will be eliminated*per unit time* - e g 5 mg of drug will be eliminated every 4 hours
- Unfortunately , when drugs reach toxic doses , their elimination slows down from
**First order into Zero order kinetics**

- occur when
**Half-life (t1/2)**- Half-life is the
**time it takes**for the plasma drug concentration toThis concept a*be reduced by 50%.**pplies only*to**drugs eliminated by****first-order kinetics**. - Half-life is determined from the
**log plasma drug concentration versus time**profile for drugs fitting a*one-compartment*model or from the*elimination phase for drugs fitting the two com- partment model* - As long as the
**dose administered***does not exceed*the**capacity of the elimination**systems (i.e., the dose does not saturate those systems), the**half-life will remain constant.** **2 Formulas you need to know for exam (High yield Facts )****t**_{1/2 }**=****0.693/k****t**_{1/2}**=****0.693****X****V**_{d}/CL.- Half-life (
**t**_{1/2)} **elimination rate constant (k)**- volume of distribution (Vd)
- clearance (CL)

- Half-life (

- For therapeutic doses of most drugs in which first-order elimination occurs,
**>95% of the drug**will be eliminated in a time interval equal to*five half-lives*

- Half-life is the
- Multi dose kinetics
- Repeat administration
- If a drug that is
**eliminated by first-order kinetics**is administered repeatedly (e.g.,one tablet every 6 hours), theof the drug will increase until a*average plasma concentration***mean****steady-state****level**is reached. **steady-state****level**will**not occur**for drugs that exhibit*zero-order elimination*- The interval of time required to reach
is equal to*steady state***five half-lives.**

- If a drug that is
- Steady state
- Some fluctuation in plasma concentration will occur
.*even at steady state* - Levels will be at the
**high point of the steady state range***shortly after a dose is administered;* - Levels will be at the
**low point immediately***before administration of the next dose*. Hence,**steady state**designates an*average plasma concentration*and the range of fluctuations**above and below that level.** - The magnitude of fluctuations can be controlled by the
**dosing interval**- A
**shorter dosing interval***decreases*fluctuations, - A
**longer dosing interval**increases them.

- A
- On cessation of multidose administration,
**>95% of the drug will be eliminated**in a*time interval equal to five half-live*s if**first-order kinetics**applies.

- Some fluctuation in plasma concentration will occur
**Maintenance dose rate**- Maintenance dose rate is the
**dose of a drug required per unit time**to*maintain a desired steady-state level*in the plasma to sustain a specific therapeutic effect. - To determine the dose rate required to maintain an average steady-state plasma concentration of drug, multiply the
**desired plasma concentration**by the**CL**: **Maintenance**=*dose rate***Desired [drug concentration]**_{plasma }**X***Clearance (CL)***(amount / time)**= (amount / volume) X (volume / time)- How is this
**equation derived :**- To remain at steady state, the
**dose rate must equal the elimination rate** - that is, the
must equal*rate at which the drug is added to the body***the rate at which it is eliminated.** **elimination rate**= CL x [drug concentration]_{plasma.}- Therefore, because the
**dose rate must equal the elimination rate**to be at steady state,**dose rate also**equals*CL**x**Desired [drug concentration]*_{plasma}_{ }

- To remain at steady state, the
- If one administers a
*drug at the maintenance dose rat*e,**a steady state plasma concentration of drug**will be reached in**four to five half-lives.**- Don’t confuse ,this
**is four to five half-lives**,*not four to five doses*! ! ! !

- Don’t confuse ,this

- Maintenance dose rate is the
**Loading dose**- In
**which situation**do we administer a loading dose? - A
**large loading dose**may be needed initially when the**therapeutic concentration**of a drug in the plasma must be*achieved*(e.g., a life-threatening situation in which*rapidly*for the drug to reach the desired steady-state level).*one can- not wait for 5 half-lives* **Loading dose**=**Desired [drug concentration**]_{plasma}x**Vd****Amount or mass**= (mass / volume) x (volume)

- In
**Very High yield Fact for exam****Volume of distribution**decides**Loading dose****Clearance**decides**Maintainence dose**

- Repeat administration

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