TK Theory - Review Questions Flashcards
PBPK modeling
Physiological based pharmacokinetic modeling and simulation (PBPK) is a computer modeling approach that incorporates blood flow and tissue composition of organs to define the pharmacokinetics (PK) of drugs
Enzyme-inducing drugs
Eg carbamazepine
autoinduction may require increasing dosages of the drug candidate to achieve the same degree of systemic exposure over time.
In rodents, lifetime exposure to enzyme inducers may be associated with liver or thyroid tumor formation.
Long-term treatment of humans with enzyme inducers can cause osteomalacia due to increased inactivation of 1,25-(OH)2-D3, the active metabolite of vitamin D (discussed later in this section), but it is not associated with liver or thyroid tumor formation.
However, in humans, enzyme induction by one drug (the perpetrator) can augment the clearance of a concomitantly administered drug (the victim), which is a cause of drug–drug interactions.
Klaassen, Curtis D.. Casarett & Doull’s Toxicology: The Basic Science of Poisons, 9th Edition (p. 314). McGraw-Hill Education. Kindle Edition.
Elimination rate constant
(Kel) represents the fraction of the amount of chemical in body that is removed from systemic circulation per unit time.
However, the actual amount eliminated in 1 hour would be slightly less given that the amount in the body is declining continuously
Klaassen, Curtis D.. Casarett & Doull’s Toxicology: The Basic Science of Poisons, 9th Edition (p. 406). McGraw-Hill Education. Kindle Edition.
first order kinetics
elimination of a constant fraction per unit time
dependent on concentration
Bioavailabilty
fraction of non-IV dose that reaches systemic circulation
cannot be >1
Volume of distribution
proportionality constant that relates total amount of toxicant in body to plasma
Vd = Dose-IV/C0
C0 = plasma concentration at time 0
zero order kinetics
elimination of constant amount per unit time
independent of concentration
