Week 5- Pharmacokinetics of oral absorption. Pn . Khadijah Hanim Abdul Rahman School of Biological Sciences Universiti Malaysia Perlis. Systemic drug absorption from GI tract/other extravascular site depend on: - Physicochemical properties of drug -dosage form used
Pn. KhadijahHanim Abdul Rahman
School of Biological Sciences
Universiti Malaysia Perlis
Systemic drug absorption from GI tract/other extravascular site depend on:
- Physicochemical properties of drug
-dosage form used
- Anatomy and physiology of absorption site
Rate of change in the amount of drug in the body, dDB/dt = dependent on relative rates of drug absorption and elimination
Absorption phase- rate of drug absorption greater than rate of drug elimination
Elimination occurs whenever drug present- even though absorption predominates
At peak drug conc in plasma:
Plasma level-time curve of drug absorption and elimination rate processes
Immediately after time of peak drug absorption, some drug may still be at absorption site ( e.g. GI tract.
Drug at absorption site- depleted, rate of absorption approaches 0, dDGI/dt=0
(now elimination phase)- represents only the elimination of drug from the body- 1st order process.
Elimination phase- rate of change in the amount of drug in the body- described as 1st order process
Rate of drug elimination is faster than rate of absorption- postabsorption phase.
Integrate the equation- oral absorption equation- to calculate drug conc (Cp) in plasma at any time, t:
plasma level-time curve for drug given in single dose
Can be simplified:
In order to calculate Cmax- the value of tmax is determine by equation (4) and substitute to equation (2).
At later time intervals, when drug absorption completed, e-kat≈ 0, equation 2 reduce to
With equation (5), graph constructed by plotting log Cp vs. t will yield straight line with a slope of –k/2.3
With similar approach, urinary drug excretion data may be used for calculation of first-order elimination rate constant, k
Graph constructed by plotting dDu/dt vs. t, yield curve identical to plasma level-time curve
After drug absorption virtually complete, -e-kat approaches zero, equation (6) reduces to
Du∞- max amount of active drug excreted
Cumulative urinary drug excretion vs t, single oral dose. Urine samples are collected at various time period.
The amount of drug excreted in each sample is added to amount of drug recovered in previous urine sample. Total amount of drug recovered after all drug excreted is Du∞
Method of residuals
Value of ka can be obtained by using the method of residuals as described in chapter before.
Immediately after oral admin
the residual lines obtained
will intercept on the y axis at
Lag time- if 2 residual lines obtained by feathering intersect at point greater than t=0.
Second expression that describes the curve omits lag time:
At t = ∞, Cp∞= 0 (i.e. plasma conc is neglectable), total amount of drug absorbed:
Fraction of drug uabsorbedvs time using Wagner-Nelson method
Equation (10) divided by equation (11)- fraction of drug absorbed at any time:
In the Wegner-Nelson equation, Ab/Ab∞ or CRFA- eventually equal unity- 100% (even though drug may not be 100% bioavailable.