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Bioavailability studies lecture7

Bioavailability studies lecture7






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    Bioavailability studies lecture7 Bioavailability studies lecture7 Presentation Transcript

    • Bioavailability Adapted by: Sereta Campbell-Elliott B. Pharm; M Pharm. Sc Prepared By: Marcia Williams
    • 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
    • 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.
    • 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 .
    • 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.
    • Illustration of bioavailability variables
    • 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.
    • 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)
    • 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
    • Illustration of Trapezoid Method from graph
    • 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)
    • 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%
    • 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.
    • 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
    • Urine Data
    • 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%
    • 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)