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M.PHARM PRACTICE

M.PHARM PRACTICE
SRM CP CHENNAI

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    Obsity Obsity Presentation Transcript

    • Pharmacokinetic variability
    • varibility
      INTRERINDIVIDUAL VARIBILITY
      INTRAINDVIDUAL VARIBILITY
    • INTRERINDIVIDUAL VARIBILITY
      The dose required to produce action varies from indvidual to indvidual
      The doses reflect the various dosage strength in market
    • Varibility in doses
      The variability in dose of warfarin required to produce similar prothrombin action in 200 patients varies widely
    • Interindividual variability
      Change in plasma concentration of same subject when given in different occasion
      Causes-
      Age ,sex,diseases, weight, drug interaction etc
      High intrasubject variability difficult to prescribe the narrow therapeutic drugs
      If high intrasubject variability in pharmacokinetic prescribed only if it has wide subject variability
    • histogram
      A.The plateau plasma con varies widely in260 patients receiving 25mg of nortryptiline orally three times daily
      B.The con are log normally distrIbuted as seen in straight line
    • steps to Indvidlisation
    • Over view
    • Describing variability
      A,B are unimodel but C is bimodal signifying that they are are two major groups with in population With higher and lower clearance
    • Factors causing varibility
    • The development and subsequent marketing of drug
    • OBESITY
      PHARMACOKINTIC VARIBILITY
    • OBESITY
      a condition that is characterized by excessive accumulation and storage of fat in the body and that in an adult is typically indicated by a body mass index of 30 or greater
    • Drug administration
      Drug administration in obese patients is difficult because recommended doses are based on pharmacokinetic data obtained from individuals with normal weights;
    • Obesity affects
      pharmacokinetic parameters-
      volume of distribution (Vd),
      clearance (Cl)
      protein binding
      changed for some drugs
      i.v. anaesthetic drugs
      inhalational anaesthetics
      Lipophilic drugs
    • Body mass index
      body mass index n a measure of body fat that is the ratio of the weight of the body in kilograms to the square of its height in meters
    • BMI
    • Dosage regimen
    • what ‘weight
      clinician must appreciate what ‘weight’ should be used to calculate dosage:
      totalbody weight (TBW),
      lean body mass (LBM)
      ideal body weight (IBW)?
    • TBW is actual body weight
      IBW is estimated by
      x =100 for adult males
      105 for adult females
    • lbm
      The percentage of fat and lean body mass
      calculated based on
      - height(cm)
      -Weight(kg)
      -girth(inches)
      Percentage of fat = 90-2(height-girth)
    • Lean body mass
      LBM can be calculated using the formulae
    • dosage
      Mostly, dosage recommendations in the package inserts are scaled to TBW
      For obsity-
      weight can then be multiplied by the published doses scaled to TBW
      = WEIGHT×DOSE ON LABEL
    • NOMOGRAM(MALE)
      Nomogram for male patients relating total body weight (kg), height
      (cm), and gender with lean body mass (LBM) using the formula
      LBM = 1.1(weight) 128(weight/height)2.
    • NOMOGRAM (FEMALES)
      Nomogram for female patients relating total body weight (kg),
      height (cm), and gender with lean body mass (LBM) using the formula
      LBM = 1.07(weight) – 148(weight/height)2.
    • Lipophilic drugs
      HIGHILY LIPOPHILICDRUGS
      barbiturates and benzodiazepines show significant increases in Vd for obese individuals.
      .
      Less lipophilic DRUGS
      have little or no change in Vd with obesity
      Exceptions to this is remifentanil,
    • Volatile agents
      Halothane is known to have considerable deposition in adipose tissue
      hepatic metabolism- halothane hepatitis
    • Propofol
      In morbidly obese patients, the induction dose of propofol can be calculated on IBW.
      Although propofol is highly lipophilic,does not accumulate in obese patients.
      So the dosage of propofol for maintenance of anaesthesia in obese and lean same
    • Drug metabolism
      Neonates
    • neonates
      Invitro studies indicate that variability much greater in first three months of life declines to adult activity
      New born are higher for contreation toxicity due to development of delay drug metabolism
    • Enzymatic system required for drug metabolism are higher in neonates and lower in adults
      Chornic exposure of foetus to epliptic drugs leads to induction of drug metabolism enzymes
      Sulfate conjugation seems to be efficient in newborn as in adults
      Conjugation with glucornic acid reduced with increasing age
    • differences
    • Age groups
    • PROTEIN BINDING
      NEONATES
    • Protein binding
      Plasma protein binding is less in newborn than adults
      Decrease Plasma protein binding is an increase in apparent volume of distribution in newborn
      Low plasma binding is due to elevation of bilrubin
    • competatiion
      relative low plasma binding associated with elevated levels of biliubrin
      Biluburin binds with albumin and many compete with drugs binding
    • GENDER
    • sex
      Sex is an individual factor
      lead to interindividual differences in the metabolism of drugs
      drugs that are metabolized by hepatic oxidation have lower metabolic clearance and longer elimination half-lives in women who are on oral contraceptives
    • sex differences
      muscle mass,
      disposition of muscle tissue,
      vascular resistance.
      gastric motility,
      secretion,
      metabolic rate
    • PHARMACOKINETIC CHANGES
      volume of distribition and rate of metabolism changes
      Volume of distrubution for central compartment is more in males
      Peripheral compartment of liophilic drug more in females
      Ex- metablism of few drug in female oxazepam
      & metaprolol is slow in female
    • Pharmacokinetic Properties
    • references
      Pharmacokinetics in obese patients by -Lu EC De Baerdemaeker MD
      slides of Approaching the In Silico Child
      Jeffrey S. Barrett, PhD, FCP
      • Biopharmaceutics and clinical pharmacokinetics
      milogibaldi ,PhD
      • Clinical Pharmacokinetics Concepts and Applications