Basic PK and PD and Drug Modify Flashcards
Goals of pharmacotherapy
- to obtain therapeutic effect
- without or minimal side effects
- for desired duration
- in vitro
- in vivo
- *both of the above are dependent on drug concentration**
- in silico
- procedure in a controlled environment outside of a living organism (drug dose/volume of media)
- experimentation using a living organism (animal studies); (F(dose, ADME (PK))
- “performed on computer or via computer simulation”
Time course of drug exposure
measured as time dependent plasma concentration
dissolution is the key rate limiting step in absorption of some oral solid dosage forms
barriers and targets:
- anatomical
- chemical
- biochemical barriers and targets
- membranes
- body fluid; pH–> solubility and ionization
- transporters, enzymes, and receptors
Effect of different formulations on the onset time and DOA
- PK curves:
- -> formulation A; powder: reaches higher plasma concentration with faster dissolution; reaches concentration for pain relief much faster
- -> formulation B: tablets: longer dissolution, smaller plasma concentration peak
Concentration-effect relationship
-sigmoidal cuve pattern
drug plasma conc: driving force for drug activity / response THEREFORE time-course of drug reponse(PD) depends on time course of drug concentration
Time course of drug exposure: IV or PO
- Initial conc (C0): IV > PO
- Max Conc. (Cmax): IV > PO
- Area under curve (AUC): IV > PO
- terminal slope: IV = PO
- Time of maximum concentration (Tmax): IV < PO
Volume of Distribution; relates to amount of drug in the body with the measured plasma conc
weak bases –> higher Vd
EX: lowest Vd: warfarin
highest Vd: imipramine
Vd = A/Cp
Clearance (CL); volume of plasma from which drug is removed
- major clearing routes: Metabolic, Renal, and Biliary routes
- -> clearance is additive
F: bioavailability
CL=(F x Dose)/ AUC
