BIOM 3090 Lecture Notes - Lecture 9: Half-Life, Pharmacokinetics, Drug Interaction
9 Jun 2018
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Clinical Pharmacokinetics (PK)
- dynamic interactions among drug ADME determines plasma
concentration of drug and target site concentration
o equilibriums exist between drug in plasma and other
body sites
- 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
o Bioavailability (%F)
o Volume of distribution (Vd)
o Clearance
o Elimination half-time (t1/2)
- Eliminatory drug processes are usually first-order processes
o i.e. a constant fraction of the drug in the blood (body) is
eliminated per unit time
o Half-life (t1/2) can be used to describe the rate of drug elimination
o Elimination half-life = time required for blood drug concentrations to
decrease by 50%
o After 1 half-life: 50% of drug eliminated
o After 2 half lives: 75% drug eliminated
o After 3 half-lives: 87.5% drug eliminated
o After 4 half-lives: 93.75% of drug eliminated
- 99.9% of drug is eliminated from blood after 10 half-lives
- for practical (clinical) purposes, drug is considered essentially from blood
after 4-5 half-lives
- therapeutic requirements often exceed the duration of action (above MEC for
desired effects following a single dose)
o prolonging duration above MEC for desired
effects by increasing dose may produce peak
concentration that is toxic
o prolongs efficacy is usually achieved by
administering multiple small doses of drug
- effect of t1/2 on drug accumulation
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- Elimination of half-life (t1/2) provides clinicians with information regarding
frequency of drug administration needed to maintain blood drug levels in the
therapeutic range
- Elimination half life is a hybrid constant being dependent on other
independent parameters. Vd and clearance (CL)
o Factors that affect Vd or CL will affect t1/2
o T1/2 = 0.693 x Vd/CL
o T1/2 can also be derived graphically from the plot of [drug] versus
time
o If CL increases, drug decreases
- The goal of most dosing regimens is to maintain plasma drug level in the
therapeutic range for the duration of therapy
o Dosing regimens consist of the following
▪ Dose (amount of drug given in mg)
▪ Route of administration
▪ Frequency of administration e.g. q12 hours
▪ Duration of therapy (e.g. 3 days)
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