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Pharmacokinetics chapter 3

Pharmacokinetics chapter 3. Effective Drug Concentration. the concentration of a drug at the receptor site . Except for topically applied agents, this concentration is often proportionate to the drug's concentration in the plasma.

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Pharmacokinetics chapter 3

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  1. Pharmacokinetics chapter 3

  2. Effective Drug Concentration • the concentration of a drug at the receptor site . • Except for topically applied agents, this concentration is often proportionate to the drug's concentration in the plasma. • The plasma concentration is a function of the rate of input of the drug (by absorption) into the plasma, the rate of distribution to the peripheral tissues (including the target organ), and the rate of elimination, or loss, from the body.

  3. Volume of Distribution (Vd) • The volume of distribution relates the amount of drug in the body to the plasma concentration. • Vd = Amount of drug inthe body Plasma drug concentration • (Units = volume) • The Vd of drugs that are normally bound to plasma proteins can be altered by liver disease (through reduced protein synthesis) and kidney disease (through urinary protein loss).

  4. Clearance (CL) • Clearance: relates the rate of elimination to the plasma concentration: • CL = Rate of elimination of drug Plasma drug concentration • (Units = volume per unit time)

  5. Clearance (CL) • The clearance is equivalent to the extraction capability of that organ for that drug, times the rate of delivery of drug to the organ. • Thus the clearance of a drug that is very effectively extracted by an organ is often flow-limited-ie, the blood is completely cleared of the drug as it passes through the organ.

  6. Half-life (t1/2) • Half-life: is a derived parameter, completely determined by volume of distribution and clearance. • (Units = time)

  7. Time to reach SS = 5 * t1/2

  8. Dosage Regimens • A dosage regimen is a plan for drug administration over a period of time. • An appropriate dosage regimen results in the achievement of therapeutic levels of the drug in the blood, without exceeding the minimum toxic concentration.

  9. Maintenance dosage • Dosing rate = Clearance x Cp Bioavailability

  10. Loading dosage • If the therapeutic concentration must be achieved rapidly and the volume of distribution is large, a large loading dose may be needed at the onset of therapy. • Loading dose= Vd x Cp F

  11. Dosage Adjustment • When Elimination Is Altered by Disease: Renal disease or reduced cardiac output often reduce the clearance of drugs that depend on renal function • Corrected dose = Average dose x Patient's ClCr 100 mL/min

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