Famotidine (Page 2 of 5)

CLINICAL PHARMACOLOGY IN PEDIATRIC PATIENTS

Pharmacokinetics

Table 6 presents pharmacokinetic data from clinical trials and a published study in pediatric patients (<1 year of age; N=27) given famotidine I.V. 0.5 mg/kg and from published studies of small numbers of pediatric patients (1-15 years of age) given famotidine intravenously. Areas under the curve (AUCs) are normalized to a dose of 0.5 mg/kg I.V. for pediatric patients 1-15 years of age and compared with an extrapolated 40 mg intravenous dose in adults (extrapolation based on results obtained with a 20 mg I.V. adult dose).

Table 6 Pharmacokinetic Parametersa of Intravenous Famotidine

a Values are presented as means ± SD unless indicated otherwise.

b Mean value only.

c Single center study.

d Multicenter study.

Age(N=numberof patients) Area Underthe Curve(AUC)(ng-hr/mL) TotalClearance(Cl)(L/hr/kg) Volume ofDistribution(Vd )(L/kg) EliminationHalf-life(T 1/2 )(hours)
0-1 monthc (N=10) NA 0.13 ± 0.06 1.4 ± 0.4 10.5 ± 5.4
0-3 monthsd (N=6) 2688 ± 847 0.21 ± 0.06 1.8 ± 0.3 8.1 ± 3.5
>3-12 monthsd (N=11) 1160 ± 474 0.49 ± 0.17 2.3 ± 0.7 4.5 ± 1.1
1-11 yrs (N=20) 1089 ± 834 0.54 ± 0.34 2.07 ± 1.49 3.38 ± 2.60
11-15 yrs (N=6) 1140 ± 320 0.48 ± 0.14 1.5 ± 0.4 2.3 ± 0.4
Adult (N=16) 1726 b 0.39 ± 0.14 1.3 ± 0.2 2.83 ± 0.99

Plasma clearance is reduced and elimination half-life is prolonged in pediatric patients 0-3 months of age compared to older pediatric patients. The pharmacokinetic parameters for pediatric patients, ages >3 months-15 years, are comparable to those obtained for adults.

Bioavailability studies of 8 pediatric patients (11-15 years of age) showed a mean oral bioavailability of 0.5 compared to adult values of 0.42 to 0.49. Oral doses of 0.5 mg/kg achieved AUCs of 645 ± 249 ng-hr/mL and 580 ± 60 ng-hr/mL in pediatric patients <1 year of age (N=5) and in pediatric patients 11-15 years of age, respectively, compared to 482 ± 181 ng-hr/mL in adults treated with 40 mg orally.

Pharmacodynamics

Pharmacodynamics of famotidine were evaluated in 5 pediatric patients 2-13 years of age using the sigmoid Emax model.These data suggest that the relationship between serum concentration of famotidine and gastric acid suppression is similar to that observed in one study of adults (Table 7).

Table 7 Pharmacodynamics of famotidine using the sigmoid Emax model

*Serum concentration of famotidine associated with 50% maximum gastric acid reduction. Values are presented as means ± SD.

EC 50 (ng/mL) *
Pediatric Patients 26 ± 13
Data from one study
a) healthy adult subjects 26.5 ± 10.3
b) adult patients with upper GI bleeding 18.7 ± 10.8

Five published studies (Table 8) examined the effect of famotidine on gastric pH and duration of acid suppression in pediatric patients. While each study had a different design, acid suppression data over time are summarized as follows:

Table 8

a Values reported in published literature.

b Means ± SD.

c Mean (95% confidence interval).

Dosage Route Effect a Number ofPatients(age range)
0.5 mg/kg, single dose I.V. gastric pH >4 for 19.5 hours (17.3, 21.8) c 11 (5-19 days)
0.3 mg/kg, single dose I.V. gastric pH >3.5 for 8.7 ± 4.7 b hours 6 (2-7 years)
0.4- 0.8 mg/kg I.V. gastric pH >4 for 6-9 hours 18 (2-69 months)
0.5 mg/kg, single dose I.V. a >2 pH unit increase above baseline in gastric pH for >8 hours 9 (2-13 years)
0.5 mg/kg b.i.d. I.V. gastric pH >5 for 13.5 ± 1.8 b hours 4 (6-15 years)
0.5 mg/kg b.i.d. oral gastric pH >5 for 5.0 ± 1.1 b hours 4 (11-15 years)

The duration of effect of famotidine I.V. 0.5 mg/kg on gastric pH and acid suppression was shown in one study to be longer in pediatric patients <1 month of age than in older pediatric patients. This longer duration of gastric acid suppression is consistent with the decreased clearance in pediatric patients <3 months of age (see Table 6).

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