Lec 6. Bioavailability and Bioequivalence, Dr. Hoang Nguyen- Full Slides.pdf

Fundamentals of Pharmacology-COM5082 Lecture 6: Bioavailability and Design Dosage Regimen Hoang Nguyen , MD., PhD., RPh., FACHE Assistant Professor of Foundational Sciences Nova Southeastern University Dr. Kiran C. Patel College of Osteopathic Medicine (KCPCOM) Contact for questions or appointment...

Fundamentals of Pharmacology-COM5082 Lecture 6: Bioavailability and Design Dosage Regimen Hoang Nguyen , MD., PhD., RPh., FACHE Assistant Professor of Foundational Sciences Nova Southeastern University Dr. Kiran C. Patel College of Osteopathic Medicine (KCPCOM) Contact for questions or appointment: [email protected] Learning Objectives After Completion of this section of Drug Bioavailability, first year M1 students will be able to: 1. Define Pharmacokinetic parameter: Bioavailability 2. Calculate Dosage Regimen related to Loading Dose, Dosing Rate, Maintenance Dose, and Steady-State Bioavailability  The percentage of the dose of a drug that is actually absorbed into the bloodstream (blood circulation).  Factors affecting bioavailability:     Differences in drug formulation Route of administration GI absorption affect factors E.g. Pramipexole in Parkinson’s disease have favorable clinical efficacy with consistent with bioavailability. (Adapted, Lippincott Illustrated Pharmacology Review, 7th Edition, 2019) Bioavailability Calculation  Bioavailability (F)=AUC(oral)x100%  AUC (IV)  Example #1  What is the bioavailability of a drug that has an intravenous AUC of 60mg.hr/ml and an oral AUC of 20 mg.hr/ml?  F=20/60=33% Therapeutic Equivalence  Therapeutic equivalence=same effect and safety profile in the treatment of a disease/condition  May or may not be chemically equivalent or bioequivalent.  Must have comparable efficacy and safety  Example: 50mg of Zoloft is therapeutically equivalent to 50mg of Sertraline. Dosage Regimen • Purpose of a dosage regimen= reaching a target concentration (TC) that will produce the desired therapeutic effect • Ideally, the regimen remains within the therapeutic window. • Loading dose is given to quickly achieve the volume of distribution, and desired plasma level. • In order to maintain plasma concentration within therapeutic levels over a long period of time, maintenance doses may be administered. (Adapted, Lippincott Illustrated Pharmacology Review, 7th Edition, 2019) Loading Dose  Ld= CpxVd F Cp=target plasma concentration at steady-state  Disadvantages of loading doses if excess levels occur:  Increased risk of drug toxicity  Longer time for plasma concentration to fall (Adapted, Lippincott Illustrated Pharmacology Review, 7th Edition, 2019) Maintenance Dose  Maintenance dose=the plasma concentration at desired level in the long run (i.e: continuous infusion)  Dosing Rate=Cp x Cl  F  Md=Dosing Rate x Dose Interval  Md=Cp x Cl x Dose interval  F  In the liver or renal disease:  Maintenance dose is decrease  Loading dose is unchanged Steady-state  Steady-state=the time needed to reach steady state depends only on the half-life of the drug. Reached in 4-5 t1/2  At the steady state, the rate of drug administration =the rate of elimination (Rate in=Rate out) (Adapted, Lippincott Illustrated Pharmacology Review, 7th Edition, 2019) Resources  1. Basic and clinical pharmacology by Katzung, 15th edition.  2. Videos: https://sketchy.com/