Pharmacokinetics of famotidine in infants.
BACKGROUND
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.


OBJECTIVE
To characterise the pharmacokinetics of famotidine in infants.


METHODS
This was a two-part multicentre study with both single dose (Part I, open-label) and multiple dose (Part II, randomised) arms.


METHODS
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Wenning
Larissa A
LA
Merck Research Laboratories, West Point, Pennslyvania, USA. larissa_wenning@merck.com
Murphy
M Gail
MG
James
Laura P
LP
Blumer
Jeffrey L
JL
Marshall
James D
JD
Baier
John
J
Scheimann
Ann O
AO
Panebianco
Deborah L
DL
Zhong
Ling
L
Eisenhandler
Roy
R
Yeh
Kuang C
KC
Kearns
Gregory L
GL
D000284:Administration, Oral; D019540:Area Under Curve; D001682:Biological Availability; D015738:Famotidine / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D005764:Gastroesophageal Reflux / Q000188:drug therapy; D006207:Half-Life; D006635:Histamine H2 Antagonists / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate
D006635:Histamine H2 Antagonists; D015738:Famotidine