title: Famotidine disposition in children and adolescents with chronic renal insufficiency.
abstract: The pharmacokinetics of intravenous famotidine (0.5 mg/kg, maximum 20 mg) were evaluated in 18 pediatric patients (ages 1-18 years) with stable, chronic renal insufficiency. Subjects were stratified by calculated creatinine clearance (Clcr) into mild (Clcr > or = 50 to < 90 mL/min/1.73 m2), moderate (Clcr > or = 25 to < 50 mL/min/1.73 m2), and severe (Clcr < or = 10 mL/min/1.73 m2) renal insufficiency groups. Significant differences between the mild, moderate, and severe groups were found for elimination rate (Kel), apparent elimination half-life (t1/2), area under the curve (AUC), and total plasma clearance (Clp) (p < 0.01). Famotidine renal clearance (Clr) was found to be significantly different between the mild and severe groups (p < 0.05). A linear relationship was observed between Clcr and Clp (p < 0.0001; R2 = 0.70). No significant differences in nonrenal clearance (Clnr) were found between groups; however, Clnr as a percentage of Clp was significantly different in the severe group (92.9% +/- 7.3% Clnr) compared to the combined mild and moderate groups (21.9% +/- 45.6% Clnr) (p < 0.05). It was concluded that the pharmacokinetics of famotidine are significantly altered in children with chronic renal insufficiency; accordingly, dosing should be based on glomerular filtration rate (i.e., Clcr).
authors.affiliation: University of Arkansas for Medical Sciences, Arkansas Children's Hospital, Little Rock, Arkansas, USA.
authors.forename: Holly D
authors.initials: HD
authors.lastname: Maples
authors.forename: Laura P
authors.initials: LP
authors.lastname: James
authors.forename: Cindy D
authors.initials: CD
authors.lastname: Stowe
authors.forename: Deborah P
authors.initials: DP
authors.lastname: Jones
authors.forename: Emily B
authors.initials: EB
authors.lastname: Hak
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Blumer
authors.forename: Beth
authors.initials: B
authors.lastname: Vogt
authors.forename: John T
authors.initials: JT
authors.lastname: Wilson
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Kearns
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Wells
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D015738:Famotidine / Q000493:pharmacokinetics*; D006635:Histamine H2 Antagonists / Q000493:pharmacokinetics*; D006801:Humans; D007223:Infant; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D006635:Histamine H2 Antagonists; D015738:Famotidine