Excretion
 Following IV injection, approximately 70% of the dose is recovered in the urine as unchanged drug. Renal clearance averages 530 mL/min, with a total clearance of 760 mL/min. The elimination half-life is 2.0 to 2.5 hours.

Four patients with clinically significant renal function impairment (creatinine clearance 25 to 35 mL/min) administered 50 mg of ranitidine intravenously had an average plasma half-life of 4.8 hours, a ranitidine clearance of 29 mL/min, and a volume of distribution of 1.76 L/kg. In general, these parameters appear to be altered in proportion to creatinine clearance (see DOSAGE AND ADMINISTRATION).

Geriatrics
The plasma half-life is prolonged and total clearance is reduced in the elderly population due to a decrease in renal function. The elimination half-life is 3.1 hours (see PRECAUTIONS: Geriatric Use and DOSAGE AND ADMINISTRATION: Dosage Adjustment for Patients With Impaired Renal Function).

Pediatrics
 There are no significant differences in the pharmacokinetic parameter values for ranitidine in pediatric patients (from 1 month up to 16 years of age) and healthy adults when correction is made for body weight. The pharmacokinetics of ZANTAC in pediatric patients are summarized in Table 1.

Table 1. Ranitidine Pharmacokinetics in Pediatric Patients Following IV Dosing Population

(age)
 n
 Dose

(mg/kg)
 t½

(hours)
 Vd

(L/kg)
 CLp

(mL/min/kg)
 
Peptic ulcer disease

(<6 years)

(6 − 11.9 years)

(>12 years)

Adults
 6

11

6

6
 1.25 or 2.5

1.25 or 2.5

1.25 or 2.5

2.5
 2.2

2.1

1.7

1.9
 1.29

1.14

0.98

1.04
 11.41

8.96

9.89

8.77
 
Peptic ulcer disease

(3.5− 16 years)
 12
 0.13 − 0.80
 1.8
 2.3
 795 mL/min/1.73/m2
 
Children in intensive care

(1 day − 12.6 years)
 17
 1.0
 2.4
 2
 11.7
 
Neonates receiving ECMO
 12
 2
 6.6
 1.8
 4.3
T½= Terminal half-life; CLp = Plasma clearance of ranitidine.

ECMO = extracorporeal membrane oxygenation.

Plasma clearance in neonatal patients (less than 1 month of age) receiving ECMO was considerably lower (3 to 4 mL/min/kg) than observed in children or adults. The elimination half-life in neonates averaged 6.6 hours as compared to approximately 2 hours in adults and pediatric patients.

Pharmacodynamics
 Serum concentrations necessary to inhibit 50% of stimulated gastric acid secretion are estimated to be 36 to 94 ng/mL. Following single IV or IM 50-mg doses, serum concentrations of ranitidine are in this range for 6 to 8 hours.

Antisecretory Activity

1. Effects on Acid Secretion
ZANTAC Injection inhibits basal gastric acid secretion as well as gastric acid secretion stimulated by betazole and pentagastrin, as shown in Table 2.

Table 2. Effect of Intravenous ZANTAC on Gastric Acid Secretion  Time After Dose,

hours
 % Inhibition of Gastric Acid Output

by Intravenous Dose, mg
 
 20 mg
 60 mg
 100 mg
 
Betazole

Pentagastrin
 Up to 2

Up to 3
 93

47