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Summary Pharmacokinetics lectures
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Summary of 20 pages for the course Pharmacokinetics at RuG (Pharmacokinetics)
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PhakinChapter 1 and 2
Beljaars
Disposition (D) = distribution + elimination
Elimination = metabolism (M) + excretion (E)
Enteral = oral, rectal, sublingual, buccal
Parenteral = intravenous, intramuscular, intracutaneous, pulmonary, intranasal,
intra-/transdermal, inhalation.
Enterohepatic cycle: liver > bile duct > duodenum > jejunum > ileum > colon (incl
portal blood system)
Blood = plasma (incl plasma proteins) + cells (RBC, WBC, platelets) 5-6L
Plasma = water (90%) + ions + lipids + plasma proteins 55% blood volume, 3L
Serum = plasma (incl plasma proteins) but without clotting factors (fibrinogen/fibrin)
Variability in drug response: pharmacokinetics:
- Gender, race, body size
- Renal/ hepatic function
- Gastric pH
- Drug-drug interactions
- Environmental factors
- Type/degree/concomitant diseases
- Drug metabolism polymorphisms
- Medication compliance
Non-adherence to prescribed medication is a major source of variability in drug therapy
- Fail because of discontinuation of treatment
- Fail because of poor execution of dosing regimen
Digital medicine system (e.g. Aripirazole)
PhaKin
,Åberg
Chapter 3, an intravenous Bolus dose
25-11-2020
Intravenous Bolus Dose
- Quick
- Easy dose control
- No absorption > _DME
- Easier to analyse
(Apparent) Volume of distribution:
- Normally: C = amount / V
- Often not actual
- V = dose / C (only when not distributed)
Logarithm:
- Base-10 log of x is defined by: 10^y = x ; y = log10x
- Natural logarithm of x is defined as: e^y = x ; y = ln x
- Lg is always base-10 logarithm
- In excel: =LOG10(B2)
Semi-log paper:
- Y tick labelling: power of 10
First-order elimination:
Assumption: loss of drug vs amount of drug
dA / dt = - k A
- dA: change in amount of drug per unit of time
- Minus sign: change should be negative (loss)
- K: elimination rate constant, inverse time (min^-1 etc)
Amount can be related to plasma concentration via the volume of distribution:
dC / dt = - k C
ln C = ln C (0) – kt straight line with negative slope
Half-life: common measure of speed of elimination is half-life, t 1/2, the time it takes
for the concentration to halve (independent of starting time).
Clearance: loss of drug vs concentration (fluid per time unit)
- Kidney and liver main eliminating organs (extractor)
- Units: l/min, l/h etc
- Volume of fluid entering organ per unit of time: Q > amount of drug
entering organ: QC
- Fraction eliminated between 0-1 (unitless)
, Area under the curve:
Trapezoidal rule:
Divide curves into trapezoids > area of trapezoid is
Total AUC is sum of trapezoid areas.
Special AUC case: exponential decay (no lag-time):
Use for clinical trial
F = bioavailability
Fraction excreted unchanged: and thus
Plasma data: elimination rate constant from linear line in semi-log data
Common mistakes;
- No unit
- Forgot to take logarithm
- Negative rate constant
- Does not use fitted line
Phakin
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