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Bioavailability studies lecture7

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  • 1. Bioavailability Adapted by: Sereta Campbell-Elliott B. Pharm; M Pharm. Sc Prepared By: Marcia Williams
  • 2. What is a drugs’ bioavailability?
    • - Rate and (relative) amount of a dose of a drug that reaches systemic circulation intact
    • May be affected by:
    • - physiological factors
    • - formulation/manufacturing factors
    • - physicochemical properties of active
    • drug
  • 3. Assessment of Bioavailability
    • Cannot assess precise concentration at site of action
    • Assumption that conc. of drug in body fluids such as plasma, urine or saliva over a period of time after administration correlates with the clinical efficacy of the drug’s therapeutic action.
  • 4. Important parameters in bioavailability studies
    • Time to Peak (T max ): the time after admin that it takes for the drug to reach C max. This is an indication of the rate of absorption.
    • Max. conc. Attained (C max ): assesses whether conc. is in therapeutic range
    • Area Under the Curve (AUC): Total drug abs. - reflects changes in distr. metabolism & excret
    • Onset of Action: The time required to reach the MEC. following drug admin .
    • Duration of Action: The time period in which the plasma conc. Exceeds MEC.
    • Intensity : the difference in the MEC and C max .
  • 5. Important parameters in bioavailability studies (cont’d)
    • Absorption rate conctant (k a ): assesses the rate of drug absorption from a formulation
    • Minimum Effective Concentration (MEC): minimum plasma conc. that must be reached before achieving therapeutic effect.
    • Maximum Safe Concentration (MSC): the conc. above which toxic effects are seen.
    • Minimum Toxic Concentration (MTC): The minimum concentration at which the toxic effect of the drug is seen.
    • Therapeutic Range: Plasma conc. range bet. MEC and MSC.
  • 6. Illustration of bioavailability variables
  • 7. Representation of Bioavailability Data
    • Construction of plasma concentration vs time curve.
    • Initial rise in curve indicates that drug is absorbed at a faster rate than it is metabolized or excreted. (absorption phase)
    • It continues to rise until a peak conc. is obtained (C max ) - rate of absorption = rate of excretion.
  • 8. Representation of Bioavailability Data(cont’d)
    • At the beginning of the descending portion of the curve, both absorption and elimination is taking place - elimination is faster.
    • After a time absorption ceases and the conc. of drug in plasma is determined only by the rate of elimination. (the elimination phase of the curve)
  • 9. AUC Measurement
    • Most common method is the trapezoid method
    • For each trapezoid [AUC] = C n-1 + C n (t n – t n- 1)
    • 2
    • AUC total = AUC extrap + AUC 0-t
    • where AUC extrap = C last /k el
  • 10. Illustration of Trapezoid Method from graph
  • 11. AUC Measurement 4.10 5 6.77 4 11.1 3 18.4 2 30.3 1 38.9 0.5 Plasma Conc (  g/ml) Time (hr)
  • 12. Absolute and Relative Bioavailability
    • Absolute Bioavailability (B A )
    • The fraction of the administered dose which is absorbed intact into the systemic circulation .
    • B A = (Auc tab /AUV IV ) x 100%
    • F = fraction of drug absorbed
    • Relative Bioavailability (B R )
    • A measure of the fraction of a given drug that is absorbed intact into the systemic circulation from a dosage form relative to a recognized standard dosage form of that drug.
    • B R = (AUC test(oral) /AUC std,(oral) ) x 100%
  • 13. Urinary Drug Excretion Data
    • Measures conc. of intact drug &/or its metabolite in the urine.
    • Collection of urine is easier and less unpleasant for the patient than collection of blood samples.
    • Conc. Of drug in urine is higher than in blood.
    • Lower conc. of protein & other endogenous substances makes drug assay easier.
    • Useful only if drug is extensively excreted in the urine and rate of excretion is proportional to the conc. of drug in plasma.
  • 14. Urinary Drug Excretion Data (cont’d)
    • Drug excreted in urine will not be proportional to conc. in plasma if the drug or its metabolites are:
    • excreted by active transport.
    • weakly acidic or weakly basic - since rate of excretion will depend on the pH of the urine.
    • Urine flow determines excretion rate.
    • E r (mcg/hr) = Amt of drug
    • time interval
  • 15. Urine Data
  • 16. Urine Data
    • Time for the maximum rate of excretion is an index of the rate of bioavailability
    • The total cumulative amount of drug excreted in the uring is an index of the extent of bioavailability
    • B A = (D’ u (oral) /D’ u IV ) x 100%
    • B R = (D’ u test(oral) /D’ u std(oral) ) x 100%
  • 17. The following tetracycline plasma and urinary data are obtained following intravenous administration of 250 mg tetracycline to a 70 kg subject: 62.0 73     8.0 13 0.90 12 10.0 11 1.05 10 12.0 9 1.2 8 13.0 7 1.50 6 16.6 5 1.71 4 29.4 3 2.40 1.5 X,urine (mg) t(h) C,plasma (ug/ml) t(h)

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