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Flashcards in Pharmacokinetics III Deck (29):

What is the most important organ in drug elimination?



What three factors affect drug elimination via the kidney and how do they relate to each other?

Glomerular filtration + tubular filtration - tubular reabsorption = kidney elimination


What is the equation for clearance (CL)?

CL = Rate of elimination of drug (mg/hr) / Plasma drug concentration (mg/L)


What is clearance?

the amount of plasma that is cleared of a drug per unit time
(rate of drug elimination)


How do drugs get cleared?

- zero-order kinetics
- first-order kinetics


What is zero-order kinetics?

the rate of elimination is constant regardless of concentration (i.e., ethanol and high doses of aspirin and phenytoin)

*fixed amount of drug that can be handled at any one time


What is first-order kinetics?

the rate of elimination is proportionate to the concentration (i.e., the higher the concentration, the greater the amount of drug eliminated per unit time)

*a constant fraction of drug is metabolized per unit of time
*majority of drugs cleared via first-order kinetics


Log transformation of first-order kinetics gives a linear relationship and helps easily determine what?

the drug's half-life


How do you get initial plasma concentration (C0)?

back-extrapolate from linear portion of log graph



How does half-life relate to volume of distribution (Vd) and clearance (CL)? (units = time)

half time = 0.693 * Vd / CL

*take two points on the linear portion of the curve, determine half-life
*remember, Vd = dose (mg) / Cp (mg/L) ; CL = elimination (mg/hr) / Cp (mg/L)

*back-extrapolate for C0, this is Cp


Why do you back-extrapolate?

To overcome for the initial distribution phase of the drug
*we are assuming that is the concentration of the drug if it had initially completely dissociated


What is multicompartment distribution?

after absorption, many drugs undergo an early distribution phase followed by a slower elimination phase


When do you reach steady state concentration (C_ss)? What is the significance of Css?
(drug accumulation with repeated dosing)

- after about 5 half-lives
- amount of drug delivered is equal to the amount metabolized and eliminated


Half-life determines the rate at which _____ concentration rises during constant infusion.



What is the equation for Average Plasma Concentration at Plateau?

Average Plasma Concentration at Plateau = F/CL * Dose/Dosing Interval


What will increase the plasma half-life?

- increase Vd (take longer to get drug back out of all the tissues and clear)
- decrease CL


What are two conditions which reduce the clearance of drugs?

- renal disease
- reduced cardiac output

*corrected dose = average dose * patient's creatinine clearance / (100 ML/min)
* normal creatinine clearance


Is drug elimination the same as saying drug termination?

drug can be terminated before getting eliminated (ex: inhibition?)


What is the normal creatinine clearance?

100 mL/min = 6 L/hr

*men: 97-137 mL/min
*women: 88-128 mL/min
*each decade of age corresponds to a decrease of about 6.5 mL/min


Can a drug with a half life of 30 minutes still have effects 48 hours after administration?

- depends on metabolites - it may have a longer half life; is active for longer than parent drug
- irreversible binding to a receptor, body has to make new receptor, so effect can be extended out longer than drug's half-life


What is dose regimen?

a plan for drug administration over a period of time
- need to achieve therapeutic levels of the drug in the blood, without exceeding the minimum toxic concentration


After giving loading dose, how do you maintain patient at desired plasma concentration?

maintenance dose


How does large Vd affect loading dose? What is equation for loading dose?

if therapeutic dose must be achieved rapidly and the Vd is large, a large loading dose may be needed to onset therapy

Loading Dose = Vd * Cp,desired / bioavailability

Cp,desired = desired plasma conc = Cpss = plasma conc at steady state


What is maintenance dose?

maintenance rate of drug administration is equal to the rate of elimination at steady state, the maintenance dose is a function of clearance

maintenance dose = CL * desired plasma concentration / bioavailability


What does biotransformation typically accomplish?

typically results in conversion of the foreign compound into a form that is more water soluble and can be excreted in the urine

*mostly occurs in liver


What is the most important organ for excretion of drugs and their metabolites?



In zero-order kinetics, when the drug dose is increased, what happens to the elimination half-life?

it increases
(if there is more drug, it will take longer to eliminated because rate of elimination is constant)


When steady state is reached and rate of input equals elimination, what is the equation for plasma concentration at steady state (Css)?

Plasma concentration at steady state (Css) = Rate of Input / CL


For patients with reduced elimination of a drug (ex, due to impaired renal or liver function), what changes should be made to the rate of input?

Rate of input may need to be decreased in order to achieve the same plateau level

*time to steady state may be prolonged in these patients due to a longer half-life