Paediatric Biopharmaceutics Flashcards
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 can reduced acid secretion in neonates do?
Increase bioavailability of acid labile drugs
- increase gastric solubility of acidic drugs
- decrease solubility of basic drugs
What can impact the amount of liquid a patient is likely to take?
saliva flow and stomach volume
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
What happens to permeability as you age?
Decreases
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
What is relative bioavailability?
Comparing Cmax and AUC between 2 products
What is bioequivalence?
Assessment of statistical equivalence of Cmax and AUC from 2 different products using confidence intervals and approach
What is formulation bridging necessary?
- Allows you to select an appropriate dose
- Allows you to make adjustments for children with chronic conditions who’s treatment may be life long
What is a relative bioavailability study?
A study done on healthy adult volunteers - comparison between adult and paediatric formulations
Why can paediatric formulations be a problem?
Most pharmacokinetic data available is for adults and children have physiological differences
What can in silico physiology based pharmacokinetics modelling be used for?
To predict formulation performance
What is the typical approach for in silico PBPK?
Develop and validate a model based on adult data then alter physiological parameters
How can food alter formulation performance and drug absorption?
- Altered composition of GI fluid
- Different gastric emptying rates
- Altered blood flow
- Drug binding to food (affects PK)
What effect can mixing food and medicines have?
- Can affect pH dependent release
- Dissolution / release rate
- Stability of API
