RX523 Pharmacokinetics in Pediatric Patients

Gestational age (GA)

Estimation of maturity at birth, measured in weeks

Post-natal age (PNA)

Chronological age in days, weeks, months, years since birth

Neonate

PNA < 1 month

Pre-term neonate

GA < 37 weeks

Full-term neonate

GA ≥ 37 weeks

Infant

1 to 12 months

Child

1 to 12 years

Adolescent

13 to 17 years

Adult

> 17 years

How does gastric pH affect absorption in pediatrics?

- Neutral at birth

- Increased bioavailability of acid-labile drugs

- Decreased bioavailability of weak acids

- Reaches adult pH around age 2

How do gastric emptying time and intestinal motility affect absorption in pediatrics?

- Prolonged gastric emptying time

- Decreased intestinal motility

- Decreased rate of oral drug absorption

- Increased time to peak concentration

How do gut wall metabolism and transporter activity affect absorption in pediatrics?

- Immature CYP enzymes

- Decreased gut wall metabolism

- Increased bioavailability

How does percutaneous drug administration change in pediatrics?

- Increased extent of absorption

- Thinner stratum corneum

- Greater perfusion and hydration of the epidermis

- Higher total BSA-to-body-mass ratio

- Possibility for toxicity

How does intramuscular drug administration change in pediatrics?

- Reduced rate of absorption in neonates

- Increased time to peak concentration

- Decreased muscle mass and blood flow

- Insufficient muscular contractions

- Unpredictable absorption

How does body composition impact drug distribution in pediatrics?

- Increased total body water and extracellular fluid

- Decreased total body fat

How do distribution pharmacokinetics change in pediatrics?

- Increased Vd for hydrophilic drugs

- Decreased Cmax concentrations

- Increased loading doses may be required

- Lipophilic drugs may have smaller Vd in infants

How do plasma protein concentrations impact drug distribution in pediatrics?

- Decreased plasma protein concentrations

- Decreased binding affinity

- Displaced by competitive endogenous substances in neonates

- Increased fu and Vd

- Possibility for toxicity

How is Phase I metabolism changed in pediatrics?

- CYP3A4 has low activity at birth, better than adults in older children

- CYP1A2 has negligible activity at birth

- CYP2D6 has low activity, weight-based doses should be decreased

- CYP2C9 and CYP2C19 have low activity at birth, genetic polymorphisms

How is Phase II metabolism changed in pediatrics?

- UGT is deficient at birth, weight-based doses should be decreased

- NAT-2 has low activity at birth, genetic polymorphisms

- Sulfation is well-developed at birth

How is kidney function changed in pediatrics (all low/immature at birth)?

- GFR matures between 8-12 months

- ATS matures around 15 months

- TR matures around 2 years

What is normal urine output for pediatric patients?

1-2 mL/kg/hr

Which statement accurately describes a commonly occurring developmental characteristic that may impact drug metabolism in a neonate or infant?

CYP2D6 enzyme activity is low at birth.

Which statement accurately describes a commonly occurring developmental characteristic that may impact drug distribution or protein binding in a neonate?

Albumin concentrations are lower in neonates compared to children.

Which statement accurately describes a commonly occurring developmental characteristic that may impact drug excretion in a neonate or infant?

Infants have a greater CrCl compared to neonates.

Which statement accurately describes a commonly occurring developmental characteristic that may impact oral drug absorption in a neonate?

Increased gastric pH

Match the route of drug administration with the predicted absorption effect on pharmacokinetic parameters for a neonate patient.

Oral

Increased Tmax

Match the route of drug administration with the predicted absorption effect on pharmacokinetic parameters for a neonate patient.

Intramuscular

Decreased F

Match the route of drug administration with the predicted absorption effect on pharmacokinetic parameters for a neonate patient.

Percutaneous

Increased F