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Pharmacokinetics and pharmacodynamics of famotidine in infants
L P James1, T Marotti, C D Stowe
1University of Arkansas for Medical Sciences and Arkansas Children's Hospital, 800 Marshall Street, Little Rock, AR 72202, USA.
Insights
Intravenous famotidine (famotidine) pharmacokinetics were studied in 10 neonates. Famotidine showed prolonged elimination half-life and reduced clearance in infants compared to older children and adults.
Area of Science:
- Pharmacology
- Neonatal Medicine
- Gastroenterology
Background:
- Stress ulceration prophylaxis is crucial in neonates.
- Understanding famotidine's behavior in infants is vital for safe and effective dosing.
Purpose of the Study:
- To evaluate the pharmacokinetics and pharmacodynamics of intravenous famotidine in neonates.
- To compare famotidine's pharmacokinetic parameters in infants with those in older children and adults.
Main Methods:
- Ten infants (5-19 days old) received a 0.5-mg/kg intravenous famotidine infusion.
- Serum, urine, and gastric pH levels were monitored.
- Pharmacokinetic parameters including Cmax, t1/2 beta, Vdss, Cl, and ClR were calculated.
Main Results:
- The mean elimination half-life (t1/2 beta) was 10.51 hours, and apparent volume of distribution (Vdss) was 0.82 L/kg.
- Plasma clearance (Cl) was 0.132 L/hr/kg and renal clearance (ClR) was 0.093 L/hr/kg.
- Famotidine's half-life was prolonged, and clearance/distribution were reduced compared to adults and older children.
Conclusions:
- Neonates exhibit significantly different famotidine pharmacokinetics compared to older populations.
- These findings suggest a need for adjusted famotidine dosing regimens in neonates.
- Further research is warranted to optimize famotidine therapy for stress ulcer prophylaxis in this age group.
Abstract:
The pharmacokinetics and pharmacodynamics of intravenous famotidine were evaluated in 10 infants ranging from 5 to 19 days of age who had a therapeutic indication for the prophylactic treatment of stress ulceration. After a 0.5-mg/kg infusion of famotidine, timed serum (n = 6), urine (24-hour collection), and repeated measurements of gastric pH were obtained. The mean +/- standard deviation maximum plasma concentration (Cmax) was 640.66 +/- 250.66 ng/mL, the elimination half-life (t1/2 beta) was 10.51 +/- 5.43 hours, and the apparent volume of distribution at steady state (Vdss) was 0.82 +/- 0.29 L/kg. Plasma clearance (Cl) and renal clearance (ClR) were 0.132 +/- 0.061 L/hr/kg and 0.093 +/- 0.056 L/hr/kg, respectively. No significant correlations were found between t1/2 beta, Vdss, Cl, and ClR and age. Six of the nine infants who had intragastric pH monitoring maintained a gastric pH > 4 until the final 24-hour sampling point. In this study, the t1/2 beta of famotidine was prolonged and the Vdss, Cl, ClR were reduced compared with corresponding parameters in previously reported studies of children older than one year of age and adults.