Pharmacokinetics Flashcards
Four components of pharmacokinetics
ADME
Absorption
Distribution
Metabolism
Excretion
Distribution
Parenteral
Avoiding the epithelial barrier
Bioavailability
Absorption pH dependency
Weak acids are better absorbed in the ____. Weak bases are better absorbed in the ____.
Weak acids are better absorbed in the stomach. Weak bases are better absorbed in the duodenum.
Common drug barriers
Effects of chemical affinity on biodistribution
Drug halflife
Volume of distribution
Vd is calculated by ____.
Vd is calculated by dividing the administered dose by the plasma concentration at time zero
Calculating a loading dose
C0 x VD
Clearance
Where elimination is the sum of metabolic and excretory elemination.
Calculating dose/time
Clearance x Target concentration
phase I and phase II hepatic metabolism
Excretion by kidney
Glomerular filtration
Drugs enter the kidney through renal arteries, which divide to form a glomerulus. Free drug (not bound to albumin) flows through the capillary slits into Bowman’s space as part of the glomerular filtrate. Since polar molecules are less likely to be bound to albumin, they are more likely to be filtered, which will help them to be excreted in the urine.
Proximal tubular secretion
Drugs that were not transferred into the glomerular filtrate leave the glomeruli through efferent arterioles, which divide to form a capillary plexus surrounding the nephric lumen in the proximal tubule. Drugs may then be actively secreted back into the glomerular filtrate in the proximal tubule. There are pumps that can move highly charged molecules (the result of phase 2 metabolism) into the proximal tubule.
Distal tubular reabsorption
As a drug moves toward the distal convoluted tubule, its concentration increases and exceeds that of the perivascular space. The drug, if uncharged, may diffuse out of the nephric lumen, back into the systemic circulation. In contrast, charged metabolites will remain in the urine, again indicating the importance of phase 2 drug metabolism that makes molecules more polar.
First vs Second Order Elimination Kinetics
Elimination Kinetics Equations
Zero-order kinetics occurs when ___. First-order kinetics occurs when ___.
Zero-order kinetics occurs when the enzyme is saturated with substrate and is working at Vmax. First-order kinetics occurs when the enzyme is not satuated and reaction rate falls as substrate concentration falls.
Clearance can best be defined as. . .
The volume of plasma that is cleared of drug per unit time
