Dosage Regimen: Dosage Regimen ALOK SINGH M. PHARM PowerPoint Presentation: How much drug are you going to give? (dose) How often will you give the drug? (dosage regimen) Approaches:: Approaches: Empirical Kinetic Empirical approach: Empirical approach Involves administration of a drug in a certain quantity, noting the therapeutic response After which the dosage and the dosing interval modified Empirical approach: Empirical approach Employed when the drug concentration in serum or plasma does not reflect the concentration of drug at the receptor site in the body Empirical approach: Empirical approach Pharmacodynamic effect of the drug is not related (or correlated) with the receptor site serum levels is not proportiona l to the clinical outcome Empirical approach: Empirical approach Anticancer drugs Warfarin = INR (International Normalized Ratio) Dopamine drip = central venous pressure Insulin sliding scale = RBS Pharmacokinetic approach: Pharmacokinetic approach Assumption: therapeutic & toxic effects are proportional to the plasma conc. of drug at the receptor sites or amount of drug in the body Pharmacokinetic approach: Pharmacokinetic approach Knowledge on the ADME of the drug from a single dose can determine or estimate the plasma levels of it when given at multiple doses Factors that determine a dosage regimen: Factors that determine a dosage regimen Activity-Toxicity of the drug Minimum therapeutic dose/MEC Toxic dose/MTC Therapeutic index Side effects Dose-response relationship Factors that determine a dosage regimen: Factors that determine a dosage regimen Pharmacokinetics Absorption (rate of diffusion, dissolution, disintegration, gastric emptying time) Distribution (protein-binding) Metabolism (biologic half-life) Excretion (drug clearance) Factors that determine a dosage regimen: Factors that determine a dosage regimen Clinical Factors Clinical state of the patient Age, weight, urine pH Condition being treated Existence of other disease state Factors that determine a dosage regimen: Factors that determine a dosage regimen Clinical Factors 2. Management of therapy Multiple drug therapy Convenience of regimen Compliance of the patient Factors that determine a dosage regimen: Factors that determine a dosage regimen Tolerance-dependence Pharmacogenetics Drug interactions Dosage form and route of administration Cont…..: Cont….. Administration may be given once for its desired therapeutic effect (e.g. antihelmintic medications) or for a period of time through multiple doses Goal for Multiple Doses: Goal for Multiple Doses Maintain the plasma or serum concentration (Cp) within the therapeutic index . A drug will accumulate in the body when the dosing interval is less than the time needed for the body to eliminate a single dose. Scenario: Scenario 50 mg drug with a half life of 12 hours with a dosing interval of 8 hours. Important variables : Important variables Dose size (D) Dosing interval (t) Mean steady state blood conc. Maximum state blood conc. Minimum steady state conc. Principle of superposition: Principle of superposition Assumes that early doses of the drug do not affect the pharmacokinetics of subsequent doses Plasma levels after the 2 nd , 3 rd or nth dose will overlay or superimpose the blood level attained after the (n-1)th dose Principle of superposition: Principle of superposition Allows one to project the plasma conc.-time curve of a drug after several doses based on the plasma conc.-time curve obtained from a single dose Assumption:: Assumption: Drug is eliminated by first-order kinetics Pharmacokinetics of the drug after a single dose (first dose) is not altered after taking multiple doses Superposition cannot be applied: Superposition cannot be applied Pathophysiology of the patient Saturation of the drug carrier system Enzyme induction or inhibition Steady state concentration: Steady state concentration The amount of drug lost per interval is replaced when the drug is given again. Consequently, the Cp of the drug found between a minimum conc. & a maximum conc. Steady state concentration: Steady state concentration AUC of the dosing interval during the steady state = AUC for a single dose It is optimal to TARGET dosing so that the conc. resides within the therapeutic index Considerations in designing a dosage regimen: Considerations in designing a dosage regimen Assumed that all pharmacokinetic parameters are constant. In case one of this factors are changed, dosage regimen is no longer valid Considerations in designing a dosage regimen: Considerations in designing a dosage regimen Change in urinary pH can cause deviation of blood levels from calculated ones Change in renal function will prolong elimination of drugs (excreted in unchanged form via the kidneys) = blood creatinine / creatinine clearance Considerations in designing a dosage regimen: Considerations in designing a dosage regimen Change in hepatic clearance due to liver disease or saturation of metabolic pathways, enzyme induction or enzyme inhibition can alter the elimination of drugs References: References 1.Chain Y W .,’Novel Drug Delivery systems –Fundamentals , Development, Development concepts.’ Biomedical Assessment , Marcel Dekker , New York. 2.Gennaro A. R . ‘Remington, the science& Practice of Pharmacy,’ Lippincott , Williams & Wilkins. Conti….: Conti…. 3. Rolland A. ‘Particulate carriers ; therapeutic Application,’ Marcel Dekker, New York. 4. D. M. Brahmankar & Sunil B. Jaiswal ; Biopharmaceutics &pharmacokinetics PowerPoint Presentation: THANK YOU!!!