Pharmacokinetics: clinical Flashcards
What determines plasma concentration of drug and target site concentration
Dynamic interactions among drug ADME
Fundamental tenet of clinical pharmacokinetics is a
relationship exists between a drugs pharmacological effects and concentration of drug in blood or plasma
Four key parameters govern drug disposition (PK) and dosage regimens
-Bioavailability (%F)……..previously discussed
-Volume of distribution (Vd)…….previously discussed
-Clearance………previously discussed
-Elimination half-life (t1/2 )
Eliminatory drug processes are usually __________ processes
First-order; a constant fraction of the drug in the blood (body) is eliminated per unit time
How many half-lives is drug considered essentially eliminated from blood
4-5 half-lives
Elimination half-life
Time required for blood drug concentrations to decrease by 50%
True of false: Half-life depends on dose or blood drug concentration
False: does NOT depend on dose or blood drug concentration
MEC
minimum effective concentration
What happens if duration is prolonged above MEC for desired effect by increasing dose
May produce peak concentration that yields adverse effects
Prolonged eddicacy is usually achieved by
administering multiple small doses of drug maintaining drug concentration above MEC for desired effects
Do drugs with short half-lives accumulate
Do not unless administered frequently
Drug given after every half life: when is steady state reached
Drug accumulation is greater when drug given every half life; plateau or steady state is reached
after ~5 half lives ie. drug input equals drug eliminated
Elimination half-life provides clinicians with information regarding
frequency of drug administration needed to maintain blood drug levels in the therapeutic range
Elimination half-life equation
t1/2 = (0.693 x Vd)/CL
The goal of most dosing regimens is to
Maintain plasma drug
level in the therapeutic range for the duration of therapy
Dosing regimens consist of the following:
- Dose (amount of drug given in mg)
- Route of administration
- Frequency of administration eg q12 hrs
- Duration of therapy eg. 3 days
Loading doses can be used to
Achieve target therapeutic drug levels quickly
Dose loading equation
DoseLoading = Vd x Csteady state / %F
Maintenance doses are given to
maintain drug levels in the target therapeutic range
Maintenance dose equation
Dosemain = CL x Csteady state / %F
Factors (physiologic, disease and drug factors) will have effects predominately on elimination t1/2 through changes in……..
-Volume of distribution
-Clearance
Alteration to PKs can result clinically in adverse drug effects
-achieving too high drug levels in the blood and toxicity
-failure to achieve adequate drug levels in the blood and subtherapeutic failure
What factors decrease volume of distribution (either increase or decrease) and how this affects half-life
Aging: decrease distribution (decrease muscle mass) –> decrease half-life
Obesity: Increase distribution (increase adipose mass) –> increase half-life
Pathologic fluid: increase distribution –> increase half-life
What factors affect clearance and how does this affect half-life
Cytochrome P450 induction (increase metabolism) –> decrease half-life
Cytochrome P450 inhibition (decrease metabolism) –> increase half-life
Cardiac failure (decrease clearance) –> increase half-life
Hepatic failure (decreased clearance) –> increase half-life
Renal failure (decreased clearance) –> increase half-life
