Pharmacokinetics and Pharmacodynamics of Famotidine in Children

Abstract

The pharmacokinetics and pharmacodynamics of intravenous famotidine were studied in 12 children (1.1-12.9 years of age; mean weight +/- standard deviation = 27.6 +/- 21.2 kg) who were given the drug for prophylactic management of stress ulceration. After a 0.5-mg/kg infusion of famotidine, timed blood (n = 10) and urine (n = 6) samples and repeated evaluations of intragastric pH (n = 13) were obtained from each subject. Pharmacokinetic parameters were determined from curve fitting of serum concentration data. The mean (+/- SD) maximum serum concentration (Cmax) was 527.6 +/- 281.2 ng/mL, the elimination half-life (t1/2) was 3.2 +/- 3.0 hours, and the apparent steady-state volume of distribution (Vdss) was 2.4 +/- 1.7 L/kg. Plasma clearance (Cl) and renal clearance (ClR) were 0.70 +/- 0.34 L/hr/kg and 0.43 +/- 0.24 L/hr/kg, respectively. Over 24 hours, 73.0 +/- 27.3% of the dose was excreted unchanged in the urine (Fel). Pharmacodynamic analysis of gastric pH data using the sigmoid Emax model predicted that 50% of the maximal effect of famotidine (EC50) occurs at a serum concentration of 26.0 +/- 13.2 ng/mL. Children who did not have an initial intragastric pH < or = 4 did not have a significant response in pH after receiving famotidine. Although Vdss and Cl were higher in these children than those seen in adults, statistically significant relationships between these parameters and age were not observed in the study population. The pharmacodynamics and pharmacokinetics of famotidine in children older than one year of age appear to be similar to those noted in adults.

Pharmacokinetics and Pharmacodynamics of Famotidine in Paediatric Patients

“…1). [4] Simil ar values for t l / 1 were obtained in the Jame s et al [4] study (table I) and that of Krau s et al [2] Howe ver, our study differed from earli er paediatric stud ies in that we observed larger value s for CL , renal clearance (CL R ) and V ss than had been reported previously. While our values for Vss and CL were higher that those reported from adult studies, statistically significant correlations between these parameters and age were not observed.…”

Oral sodium citrate increases nausea amongst elective Cesarean delivery patients

“…16 Histamine-2 blockers, including famotidine, are frequently used in infants to treat gastroesophageal reflux or prevent stress ulceration. 17,18 In conclusion, nausea during Cesarean delivery is more frequent in women receiving oral sodium citrate rather than iv famotidine. Therefore, we recommend the preoperative use of a histamine-2 blocker rather than oral sodium citrate to neutralize maternal gastric acidity in parturients scheduled for elective Cesarean delivery under spinal anesthesia.…”

Assessment of Age-Related Changes in Pediatric Gastrointestinal Solubility

“…Such studies were additionally scrutinized to ensure their appropriateness towards defining GI parameters reflective of normal children. Investigations of gastric pH including critically ill subjects were restricted to studies where acid reducing agents (i.e., H2 antagonists) were withheld (26)(27)(28). Two pediatric studies assessing fasting gastric pepsin levels included subjects deemed as critically ill (29,30).…”

“…Average (mean) values pertaining to neonates (0-28 days) and infants (1-12 m) are illustrated for reference (red -x's). (b) Fasting gastric pH amongst pediatrics (black circles) is depicted as the central tendency, either mean or median, from separate investigations (26)(27)(28)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55). Studies where gastric pH values was quantified over specific age range without denoting the group's mean age were graphically depicted using the middle of the age range.…”