Pharmacokinetics Flashcards
Process involved (LADME)
Pharmacokinetics
Transport
Liberation
Absorption
Distribution
Metabolism
Excretion
▪️ movement through the cell membrane
▪️ basic requirement: drug must be in aqueous solution except in pinocytosis where drug is in missile form
Transportation
Two types of mechanism of transport in Pharmacokinetics
- Passive Diffusion
- Carrier-mediated Transport
▪️ dominant, most common; slowest; no enery requirement
▪️ along concentration gradient (high to low)
▪️ governed by Fick’s Law Diffusion
Passive diffusion
“LUNA”
Lipophilic
Unionized
Non-Polar
Absorbed
“HIPE”
Hydrophilic
Ionized
Polar
Excreted
▪️ selectivity/ specificity- carriers recognize specific molecules
▪️ subject to competition, inhibition or antagonism
▪️ Michaelis-Menten Kinetics/ non-linear kinetics/ capacity limited
Carrier-Mediated Transport
Drug that crosses the BBB because of large neutral AA transporter (LNAAT)
Levodopa
Elimination is DEPENDENT on drug concentration
First Order
▪️Drug clearance is on a constant rate
▪️INDEPENDENT on drug concentration
Zero Order
Energy requiring; against concentration gradient (uphill); fastest
Active Transport
No energy requirement; along concentration gradient; passive diffusion with carrier
Facilitated Diffusion
Drug passes through water filled pores; only paracellular transport mechanism
Convective Transport / Bulk Flow
Important for movement or transport of large ions
Ion-Pair Transport
▪️ release of drug from the dosage form
▪️ end product: drug in aqueous form/sol’n
▪️ highly modifiable
Liberation
▪️Physiologic: rate and extent of drug disappearance from the site of administration
▪️Pharmacokinetic: rate and extent of drug entry into the systemic circulation
Absorption
Is the measure of rate and extent of drug entry into the systemic circulation / pharmacokinetic absorption
Bioavailability [BA] or [F]
2 Methods of Bioavailability
- Cumulative Urinary Excretion Data
- Drug Plasma Concentration vs Time Graph
Maximum plasma concentration; measures both rate and extent of absorption; most variable
Cmax
Time it takes to reach Cmax; measures rate only; least important
Tmax
Area under the curve; measures extent only; most important
AUC
Types of BA
▪️ same dose, different routes
Absolute Bioavailability
Types of BA
▪️ use when comparing a generic drug to a reference standard
▪️ same dose, same route particularly PO
Relative Bioavailability
Main site of drug absorption
Small intestine
Time it takes the stomach to empty its contents into the small intestine
Normal: 2-3 hours
Gastric Emptying Time (GET)
Faster Emptying, Faster Absorption, Lower
Lower GET
What Factors Increasing GET (slower absorption)
▪️high fat / protein meal, happy meal
▪️ stress
▪️ strenuous exercise (heavy)
▪️ gastric ulcers
▪️ lying on the LEFT side
▪️ anticholinergics, opioid, morphine, nalbuphine
What Factors Decreasing GET (faster absorption)
▪️ extreme temperature of food
▪️ mild exercise
▪️ DM
▪️ lying on the RIGHT side
▪️ cholinomimetics
▪️ prokinetics: domperidone metoclopramide
▪️ SAME API, salt / ester / complex and dosage form and strength
▪️ DIFFERENT in excipients used such as flavorants and colorings
Pharmaceutical Equivalents
▪️SAME API
▪️DIFFERENT salt/ester/complex, dosage form & strength
Pharmaceutical Alternative
▪️SAME API in the same dosage form and route of administration
▪️ Similar bioavailability
Therapeutic Equivalents
▪️SAME drug class
▪️DIFFERENT API
Therapeutic Alternatives
Reversible transfer of a drug from the systemic circulation to the site of action and to the other compartment
Distribution
Pharmacokinetic Parameters:
Hypothetical value of body fluid required to dissolve a given amount of drug concentration equal to that of plasma concentration
Volume of distribution (Vd)
Drugs that undergo extensive protein binding (WNMS)
Warfarin
NSAIDs (Phenylbutazone)
Midazolam
Sulfa drugs
▪️Biotransformation
▪️Primary Goal: to convert drugs into an inactive / less active non-toxic / less toxic polar, water soluble
Metabolism
Initially inactive
Prodrug
Aka Pre-systemic metabolism
First Pass Effect
▪️Final loss drug from the body
▪️Requirement: polar, water soluble
Excretion
▪️Main excretory organ
▪️Requirement: Polar; Low MW <400-600
Kidneys
▪️Slow Acetylators
▪️Fast Acetylators
▪️Caucasians
▪️Asians