Primer Intro

8/18

Pharmacokinetics

• the study of drug absorption, distribution, metabolism, and excretion (ADME)

• what the body does to the drug

Clinical Pharmacokinetics

• application of pharmacokinetic principles to ensure safe and effective therapeutic management of drugs in individual patients

• goals: high efficacy low toxicity

Absorption

drug moves from site of admin to central compartment (bloodstream)

Ultimate plasma concentration (Cp) factors

• formulation (S): salt form; immediate vs modified release

• bioavailability (F): amount of drug reaching circulation

  • impacted by route of administration + other factors

• dose administered

Bioavailability

• fraction of administered drug that is delivered to systemic circulation

• extravascular admin (PO, IM, SC)

  • drug absorbed across biological membranes before reaching vascular system

  • max conc (Cmax): rate of absorption equals rate of elim

  • concentration decreases based on HALF LIFE of drug

First pass metabolism

• IV: 100% bioavailability; does NOT pass through clearing organs, NO first pass metabolism

• PO: large amounts of drug can be lost via first-pass

Distribution

• drug moves from central compartment to site of action (tissues/organs)

Volume of Distribution (Vd)

• “apparent” bc it is an estimation based on average Vd measured in other pts with similar demographics and conditions

• related total amount of drug in body to conc of drug in plasma

• influenced by hydrophilicity and protein binding (increased hydrophilicity = lower Vd)

• useful in calculating loading dose needed to achieve steady state conc immediately after dose is administered

Protein Binding factors

• drug: physiochemical properties; total conc in body

• protein: quantity available for binding; quality/physiochemical properties of protein

• affinity: between drug/protein

• drug interactions: competition for binding sites; protein modified by another substance → changes affinity for drug

• pt pathophysiology: perfusion, uremia, hepatic disease