Pharmacokinetics of famotidine in infants

• Published in: Clinical pharmacokinetics Vol. 44; no. 4; pp. 395 - 406
• Main Authors: WENNING, Larissa A, MURPHY, M. Gail, YEH, Kuang C, KEARNS, Gregory L, JAMES, Laura P, BLUMER, Jeffrey L, MARSHALL, James D, BAIER, John, SCHEIMANN, Ann, PANEBIANCO, Deborah L, LING ZHONG, EISENHANDLER, Roy
• Format: Journal Article
• Language: English
• Published: Auckland Adis international 01-01-2005; Wolters Kluwer Health, Inc
• Subjects: Administration, Oral; Area Under Curve; Biological and medical sciences; Biological Availability; Digestive system; Famotidine - blood; Famotidine - pharmacokinetics; Famotidine - therapeutic use; Female; Gastroesophageal Reflux - drug therapy; Half-Life; Histamine H2 Antagonists - blood; Histamine H2 Antagonists - pharmacokinetics; Histamine H2 Antagonists - therapeutic use; Humans; Infant; Infant, Newborn; Injections, Intravenous; Male; Medical sciences; Metabolic Clearance Rate; Pharmacology. Drug treatments; Human; Famotidine; Infant; Antiulcer agent; Antagonist; Pharmacokinetics; Antihistaminic; H2 Histamine receptor
• ISSN: 0312-5963; 1179-1926
• DOI: 10.2165/00003088-200544040-00004

Although famotidine pharmacokinetics are similar in adults and children older than 1 year of age, they differ in neonates owing to developmental immaturity in renal function. Little is currently known about the pharmacokinetics of famotidine in infants aged between 1 month and 1 year, a period when renal function is maturing.
To characterise the pharmacokinetics of famotidine in infants.
This was a two-part multicentre study with both single dose (Part I, open-label) and multiple dose (Part II, randomised) arms.
Thirty-six infants (20 females and 16 males) who required treatment with famotidine and who had an indwelling arterial or venous catheter for reasons unrelated to the study.
Infants in Part I were administered a single dose of famotidine 0.5 mg/kg; the dose was intravenous or oral according to the judgement of the attending physician. Infants receiving 0.5 mg/kg intravenously were divided into two groups by age, and pharmacokinetic parameters in infants 0-3 months and >3 to 12 months of age were compared. Infants in Part II were randomised to one of the following treatments: 0.25 mg/kg/dose intravenously or 0.5 mg/kg/dose orally on day 1 and subsequent days, or 0.25 mg/kg/dose intravenously or 0.5 mg/kg/dose orally on day 1 followed by doses of either 0.5 mg/kg/dose intravenously or 1 mg/kg/dose orally on subsequent days. From day 2 onwards, age-adjusted dose administration regimens (once daily in infants <3 months of age and every 12 hours in infants >3 months of age) were used; the total number of famotidine doses ranged from 3 to 11 and the total number of days of dose administration ranged from two to eight.
In infants <3 months of age, plasma and renal clearance of famotidine were decreased compared with infants >3 months of age. Pharmacokinetic parameters for the older infants (i.e. those >3 months) were similar to those previously reported for children and adults. Approximate dose-proportionality, no accumulation on multiple dosing and an estimated bioavailability similar to adult values were also observed.
A short course of famotidine therapy in infants appears generally well tolerated, and the characteristics of famotidine pharmacokinetics during the first year of life are explained to a great degree by the development of renal function, the primary route of elimination for this drug.