Case Study 1
1. What is currently the dose of gentamicin that will be prescribed to this preterm infant?
Preterm infants have a large volume of distribution for drugs that are distributed into the extracellular water compartment. For that reason, the dose needed to reach an appropriate peak concentration is higher than in older newborns. However, preterm infants have an impaired renal function. Therefore, they need more time to clear the drug from their system. Therefore, 4-5 mg/kg is indicated to reach an appropriate peak concentration, but a prolonged (36 hrs) time is needed to clear the drug from this neonate’s body.
2. This time, the clearance and volume of distribution of gentamicin will be different from the clearance and volume of distribution of gentamicin during the first treatment of this young infant. What do you expect to happen?
Postnatal maturation results in an increased clearing capacity as well as a decrease in the extracellular water compartment. As a result, the clearance of gentamicin will increase, but the volume of distribution will become smaller.
3. Which statement about proton pump inhibitors is correct?
Proton pump inhibitors are dependent on different enzymes for their metabolism. In this case, pantoprazole is much more dependent on CYP2C19 than omeprazole. Therefore, the *17 genetic variant in CYP2C19 will be much more important for a different clearance of pantoprazole than of omeprazole because the latter is dependent equally on CYP2C19 and CYP3A4.
Case Study 2
What would be the best advice on dose adjustment?
Perinatal asphyxia might result in multiple organ dysfunction. In this case, renal function has been diminished due to the asphyxia. As a consequence, the clearing capacity of this newborn infant is impaired and therefore the dosing interval needs to be prolonged (frequency needs to be decreased) to assure no accumulation of gentamicin. The dose to reach efficacy does not need any adjustment.
Presented by the PhRMA Foundation Safe and Effective Prescribing Project
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