Biopharmaceutics Flashcards
Define absolute bioavailability.
Fraction of a drug that enters the systemic circulation.
What are the benefits of injectables?
Rapid response
Patient may be unconscious
Drug cannot be removed in vomiting
Good where drugs have limited oral bioavailability
Which layer of the skin is the most impermeable and hardest to penetrate?
Stratum corneum
What is the dermis?
Thick layer of tissue below the skin that is perfused by capillaries from deeper layer of arteries/veins in the hypodermis
What is the stratum corneum?
Outer layer of dead cellular material
What is the general transit time of the GIT?
12-36 hours
What are the two sites of first pass metabolism?
Liver
Intestinal wall
Describe the features of the stomach leading to minimal absorption.
Tight junctions between cells limit paracellular transport
Epithelial surface is smooth with low surface area
Describe the features of the small intestine leading to maximal absorption.
Transit time is 3-4 hours
Large surface area
Highly perfused with 25% of cardiac output
What is the splanchnic circulation?
Intestinal veins flow into portal vein
Blood rich in materials is filtered through hepatic sinusoids
What is the transit time of the colon?
2-48 hours depending on frequency of defication
Is there anything that affects transit time of the small intestine?
Independent of fed/fasted state
What is the volume of the stomach?
50mL fasted
>1000mL fed
What properties of neonatal GIT affects drug absorption/bioavailability?
Reduced acid secretion may increase bioavailability of acid labile drugs and increase solubility of acidic drugs
List the age ranges of paediatrics.
Neonate 0-27 days
Infant 1-23 months
Child 2-11 years
Adolescent 12-18 years
How does the expression of metabolising enzymes in the gut wall differ in paediatrics?
CYP3A expressed in 50% of children under 6 months
How does the expression of metabolising enzymes in the liver differ in paediatrics?
CYPs generally present from birth, reaching adult levels by 2-5 years
UGTs reach adult levels anytime from 2 years
What are the physiological changes that occur in children that can alter absorption and pharmacokinetics?
- saliva production
- gastric pH and emptying rate
- intestinal transit, SA and motility
- drug metabolising enzymes
- drug efflux transporters
What is the general trend of pH along GIT as you get older?
pH decreases
What effect does transit time have on paediatric formulations?
Irregular intestinal motility leads to variable transit times which can be a problem for controlled release formulations
How is metabolism affected in paediatric patients?
Children have a larger liver size and hepatic blood flow per body weight so there is more 1st pass metabolism and increased clearance
What is formulation bridging?
Assessing the rate and extent of absorption from one formulation vs. another
