Lecture 1: Basic Principles of Clinical Pharmacokinetics PDF

Lecture 1 Basic principles, volume of distribution, and loading dose AIMS: To revise the concepts of clinical pharmacokinetics and the meaning and relevance of volume of distribution to loading dose calculation OBJECTIVES: By the end of the session you should be able to: Explain the terms “pharmacok...

Lecture 1 Basic principles, volume of distribution, and loading dose AIMS: To revise the concepts of clinical pharmacokinetics and the meaning and relevance of volume of distribution to loading dose calculation OBJECTIVES: By the end of the session you should be able to: Explain the terms “pharmacokinetics and pharmacodynamics” Explain the term “volume of distribution” Calculate a drug loading dose from a target concentration and an estimate of volume of distribution. DEFINITION TDM is the clinical laboratory measurement of drug concentrations in plasma, serum or blood and within the time to individualize dosage so that drug concentrations can be maintained within a target therapeutic range. CONCEPT OF THERAPEUTIC DRUG MONITORING TDM is based on the principle that for some drugs there is close relationship between the plasma level of the drug and its clinical effect. The main aim of therapeutic drug monitoring is to find out an effective medication against the disease without any dangerous toxic action. The purpose of TDM is to individualize the dosage to achieve maximum efficacy of a drug and at the same time minimize adverse drug reactions. IMPORTANCE OF TDM Importance of TDM is used in 1. Assessment of the appropriate dose for drugs used as a prophylactic therapy such as seizures, cardiac arrhythmias, or organ rejection 2. to avoid serious toxicity as with the drugs that have a narrow therapeutic range, such as with the aminoglycoside antibiotics and digoxin. 3. To help predict a patients dose requirements. 4. To minimize the time period needed for dosage adjustment. 5. Assessment of the appropriate dose for drugs used as a prophylactic therapy such as seizures, cardiac arrhythmias, or organ rejection 6. to avoid serious toxicity as with the drugs that have a narrow therapeutic range, such as with the aminoglycoside antibiotics and digoxin. 7. To help predict a patients dose requirements. 8. To minimize the time period needed for dosage adjustment. Therapeutic drug monitoring The minimum effective concentration (MEC): it is the minimum concentration of the drug at the receptor to produce the desired pharmacological effect The minimum toxic concentration (MTC): it is the minimum concentration of the drug needed just to barely produce a toxic effect. Onset time: The time required for the drug to reach MEC. Duration of drug action: It is the difference between the onset of time and the time for the drug to decline back to the MEC. Therapeutic window: It is the concentration between the MEC and MTC. Peak plasma level (Cmax): It is the maximum drug concentration. Time for peak plasma level (Tmax): It is the time of maximum drug concentration in the plasma. Area under the curve (AUC): It is related to the amount of the drug absorbed systemically. Steady state: It is an equilibrium condition when the rate of drug administration equals the rate of drug removal, and the amount of drug contained in the body reaches a constant value. This condition is extremely important in clinical pharmacokinetics because usually steadystate serum or blood concentrations (Css) are used to assess patient response and compute new dosage regimens. Basic Principles of Clinical Pharmacokinetics: Pharmacokinetics: “What the body does to the drug” Absorption (input) Distribution Metabolism (liver) Excretion (kidneys) Pharmacodynamics: “What the drug does to the body” Therapeutic effects Toxic effects PK/PD relationships determine drug dosage regimens Clinical Pharmacokinetics Aim design an appropriate drug dosage regimen for an individual patient. How much should be taken? How often should it be taken? Assume “shape” of the concentration-time profile associated with maximum efficacy and minimum toxicity is known. Pharmacokinetic processes: Absorption Bioavailability (F): % of dose reaching the systemic circulation Absorption Rate (ka): speed of input into the systemic circulation Distribution Volume of distribution (V): apparent volume into which the drug distributes within the body Pharmacokinetic processes Elimination: Clearance (CL): volume cleared of drug per unit time Elimination rate constant (k): proportion of drug amount eliminated per unit time Elimination half-life (t1/2): time for concentration to fall to half Volume of distribution and loading dose