Dyslipidemia PK Flashcards
what factors make a patient more likely to experince the myopathy of statins?
old age, female, low BMI, chronic renal or liver disease, CYP3A4 inhibitors
what is Ka?
absorption rate constant = the fraction of drug absorbed into systemic circulation per unit time (NOT THE AMOUNT ABSORBED PER UNIT TIME)
rate of absorption is indicated by ___
Ka
if Ka increases, what happens to Tmax and Cmax?
Tmax decreases and C max increases
what is bioavailability?
the fraction of unchanged drug absorbed into the systemic circulation
F ranges from ___ to ___ and has no units
0-1
F is reflected by the ____ of the concentration vs time curve
area under the curve (AUC)
absolute F compares ____
AUC of a doasge form with the AUC of an IV reference standard for the same drug in the same person
relative F compares ___
to another non-IV dosage form (containing the same drug)
how to calculate absolute bioavailability
[AUC/Dose tablet A] divided by AUC/ IV ref standard
how to calculate relative bioavailability
(AUC/Dose tablet X) divided by (AUC/dose tablet A)
what is the first pass effect?
decrease in an orally administered drug at various sites (mainly small intestines and liver) before reaching the systemic circulation
reasons for decreased parent drug in the GI tract?
poor absorption, metabolism, and or efflux (reverse transport) at intestinal enterocytes
reasons for decrease in parent drug in the liver
drugs with high first pass metabolism, rapid and extensive loss (by metabolic elimination in the liver) of some drugs during their first pass through the liver (portal vein pre-systemic elimination) before reaching the systemic circulation
why do statins have lo oral F?
they are high first pass metabolism
for 2 products to be bioequivalent, the ratio for the ____ and ___ of test to reference need to be within 80-125%
AUC and Cmax
what uptake transpoters are statins substrates for?
OAT1B1 & OAT2B1
statins are substrates of whihc efflux trnasporters?
PGP and breast cancer resitance protein
fluvastatin, rosuvastatin, cerivastatin, and atorvastatin form metabolites in a ___ manner
parallel
lovastatin and simvastatin form metabolites in a ___ manner
parallel and consecutive
give 2 examples of phase 1 metabolic reactions
oxidation and hydrolysis
given some examples of phase 2 metabolic reactions?
conjugation with glucuronic acid, sulphate, acetyl coA, glutathione
where are CYP enzymes primarily found in the tissues?
mostly in the liver, also in the intestinal mucosa, kidney, lung, brain etc.
where are CYP enzymes primarily found in the subcellular level?
mainly in the smooth endoplasmic reticulum (microsomes)
