Bioavailability studies ii


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Bioavailability studies ii

  1. 1. Bioavailability II Adapted by: Sereta Campbell-Elliott B. Pharm; M Pharm. Sc
  2. 2. Determination of bioavailability parameters <ul><li>Equation to describe curve is : </li></ul><ul><li>C p = ka * FDo___ (e –kel ∆t – e -ka∆t ) </li></ul><ul><li>V D (k a – k el ) </li></ul>
  3. 3. Determination of ka <ul><li>1. Method of residuals: </li></ul><ul><li>-Plot drug conc. Vs time on semilog paper </li></ul><ul><li>Obtain slope at terminal phase </li></ul><ul><li>Extrapolate terminal phase backward to intercept with y-axis </li></ul><ul><li>Take 3 points from the extrapolated line and drop vertically to obtain values on the curve </li></ul><ul><li>Read values from the extrapolated line and curve; then plot the difference at the corresponding time </li></ul><ul><li>The straight line obtained will have a slope/gradient of -ka/2.3 </li></ul>
  4. 4. Determination of ka cont’d <ul><li>If absorption is occurring as a first order process (rate is dependent on the amount of drug remaining at the site) then the elimination phase of the curve must be used to determine k a . This minimizes errors introduced if immediately post-t max is used (as absorption is still occurring) and drug molecules are still being absorbed </li></ul>
  5. 5. Determination of ka cont’d <ul><li>The y-axis intercept of the residual lines represent a constant that incorporates: </li></ul><ul><li>k a , k el , V D and FD o and may be expressed as: </li></ul><ul><li>A = k a * FD o ___ </li></ul><ul><li>V D (k a - k el ) </li></ul>
  6. 6. Determination of ka cont’d <ul><li>The plasma conc.-time curve after oral absorption may be described by both the absorption and the elimination phase of the curve, where : </li></ul><ul><li>C p = ka * FDo___ (e –kel ∆t – e -ka∆t ) </li></ul><ul><li>V D (k a – k el ) </li></ul>
  7. 7. Determination of ka cont’d <ul><li>Wagner-Nelson Method (from unabsorbed drug) </li></ul><ul><li>After an oral dose, the total amount should be accounted for in the GIT, in the body and in urine, therefore : </li></ul><ul><li>D T = D GI + D B +D U </li></ul><ul><li>If D u + D B = Total Amt of drug abs = AB </li></ul><ul><li>Then AB = Cp * VD </li></ul>
  8. 8. Determination of variables from curve <ul><li>Therefore variables which may be obtained from the graph: </li></ul><ul><li>k el – gradient of the termination phase </li></ul><ul><li>k a – determined from residuals or from </li></ul><ul><li> y-intercept </li></ul><ul><li>C pt – drug plasma conc. at time t along the curve </li></ul>
  9. 9. Determination of F (fraction of absorbed dose) <ul><li>Value of F may be determined from above equations: </li></ul><ul><li>a) C p = ka * FDo___ (e –kel ∆t – e -ka∆t ) </li></ul><ul><li>V D (k a – k el ) </li></ul><ul><li>b) A = k a * FD o ___ </li></ul><ul><li>V D (k a - k el ) </li></ul>
  10. 10. Determination of F cont’d <ul><li>By using a derivation of the Wagner-Nelson equation </li></ul><ul><li>A max = max. amount of drug absorbed </li></ul><ul><li>If A max = V D * k el *AUC = F * Dose </li></ul><ul><li>Then, F = V D * k el *AUC </li></ul><ul><li>Dose </li></ul>
  11. 11. Determination of F cont’d <ul><li>When comparing two products and determining AUC of each, F may be calculated by comparing AUCs’ where: </li></ul><ul><li>F = AUC a / dose a_ </li></ul><ul><li> AUC b / dose b </li></ul>
  12. 12. Determination of F from Urine data cont’d <ul><li>If only urine data are available then </li></ul><ul><li>F e = __ U ∞ ___ where F e = Fraction of drug </li></ul><ul><li>F * Dose excreted unchanged </li></ul><ul><li>Therefore: </li></ul><ul><li>F = __ U ∞ ___ </li></ul><ul><li>F e * Dose </li></ul>