66
 99

77
In a group of 10 known hypersecretors, ranitidine plasma levels of 71, 180, and 376 ng/mL inhibited basal acid secretion by 76%, 90%, and 99.5%, respectively.

It appears that basal- and betazole-stimulated secretions are most sensitive to inhibition by ZANTAC, while pentagastrin-stimulated secretion is more difficult to suppress.

2. Effects on Other Gastrointestinal Secretions

Pepsin
ZANTAC does not affect pepsin secretion. Total pepsin output is reduced in proportion to the decrease in volume of gastric juice.

Intrinsic Factor
 ZANTAC has no significant effect on pentagastrin-stimulated intrinsic factor secretion.

Serum Gastrin
ZANTAC has little or no effect on fasting or postprandial serum gastrin.

Other Pharmacologic Actions
Gastric bacterial flora―increase in nitrate-reducing organisms, significance not known.
Prolactin levels―no effect in recommended oral or IV dosage, but small, transient, dose-related increases in serum prolactin have been reported after IV bolus injections of 100 mg or more.
Other pituitary hormones―no effect on serum gonadotropins, TSH, or GH. Possible impairment of vasopressin release.
No change in cortisol, aldosterone, androgen, or estrogen levels.
No antiandrogenic action.
No effect on count, motility, or morphology of sperm.

Pediatrics
The ranitidine concentration necessary to suppress basal acid secretion by at least 90% has been reported to be 40 to 60 ng/mL in pediatric patients with duodenal or gastric ulcers.

In a study of 20 critically ill pediatric patients receiving ranitidine IV at 1 mg/kg every 6 hours, 10 patients with a baseline pH≥4 maintained this baseline throughout the study. Eight of the remaining 10 patients with a baseline of pH≤2 achieved pH≥4 throughout varying periods after dosing. It should be noted, however, that because these pharmacodynamic parameters were assessed in critically ill pediatric patients, the data should be interpreted with caution when dosing recommendations are made for a less seriously ill pediatric population.

In another small study of neonatal patients (n = 5) receiving ECMO, gastric pH<4 pretreatment increased to >4 after a 2-mg/kg dose and remained above 4 for at least 15 hours.

Clinical Trials
 
Active Duodenal Ulcer
In a multicenter, double-blind, controlled, US study of endoscopically diagnosed duodenal ulcers, earlier healing was seen in the patients treated with oral ZANTAC as shown in Table 3.

Table 3. Duodenal Ulcer Patient Healing Rates  Oral ZANTAC*
 Oral Placebo*
 
 Number

Entered
 Healed/

eva luable
 Number

Entered
 Healed/

eva luable
 
Outpatients

Week 2

Week 4
 195
 69/182

(38%)†

137/187

(73%)†
 188
 31/164

(19%)

76/168

(45%)

*All patients were permitted antacids as needed for relief of pain.

†P<0.0001.

In these studies, patients treated with oral ZANTAC reported a reduction in both daytime and nocturnal pain, and they also consumed less antacid than the placebo-treated patients.

Table 4. Mean Daily Doses of Antacid  Ulcer Healed
 Ulcer Not Healed
 
Oral ZANTAC

Oral placebo
 0.06

0.71
 0.71

1.43

Patholo