Z Gastroenterol. 1988 Jul;26(7):345-50.
[Reduced suppression of gastric acid by ranitidine in severe reflux esophagitis. A pilot study]

[Article in German]

Koop H, Klein M, Bauer A, Arnold R.

Abteilung fur Gastroenterologie und Stoffwechsel, Philipps-Universitat, Marburg.

Repeated intragastric long-term pH recordings for 24 h were conducted in 13 patients with reflux oesophagitis grade III and IV (Savary and Miller) during treatment with ranitidine 150 mg b.i.d. and 300 mg b.i.d. and omeprazole 40 mg mane (n = 5). Ranitidine led to a significantly less pronounced increase in median gastric pH in oesophagitis than in healthy controls. The magnitude of intragastric pH increase showed parallelism to symptomatic response and healing. Omeprazole increased intragastric pH above 4 for 24 h and caused rapid healing in non-responders. It is concluded that in patients with severe reflux oesophagitis ranitidine is less effective in increasing intragastric pH than in controls, whereas omeprazole reveals potent antisecretory activity accompanied by rapid healing.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3223004&dopt=Abstract ranitidine






J Pharm Sci. 1988 Sep;77(9):760-4.
Effect of pH on the in vitro dissolution and in vivo absorption of controlled-release theophylline in dogs.

Vashi VI, Meyer MC.

Department of Pharmaceutics, University of Tennessee, Memphis 38163.

Dogs were used to examine the effect of elevated gastric pH on the absorption of controlled-released theophylline dosage forms with pH-dependent dissolution. In vitro studies showed that a controlled-release theophylline tablet dissolved more rapidly if it was initially exposed to an acidic media. In contrast, a controlled-release theophylline beaded capsule was slightly more rapidly dissolved in the absence of an initial exposure to an acidic media. Gastric pH was increased from 0.5-2.5 to 4.5-7.0 in four dogs by using 150-mg ranitidine HCl tablets, administered every 3 h, to induce an achlorhydric condition. Gastric pH was monitored using a Heidelberg capsule. Ranitidine was shown to have no apparent effect on the absorption or clearance of theophylline administered to the dogs as an oral liquid. The mean area under the concentration-time curve to infinity (AUCinf) for the controlled-release theophylline tablet was 21% greater (p less than 0.05) when administered to the four dogs without ranitidine treatment, compared with that following dosing with ranitidine. In contrast, the controlled-release beaded capsule exhibited a 10% greater AUCinf when ranitidine was given concomitantly. In general, ranitidine-induced changes in the in vivo absorption rate parameters for both dosage forms were opposite to those predicted from the in vitro dissolution rates. The results of this study demonstrated that the extent of theophylline absorption from controlled-release dosage forms, in control dogs and dogs with ranitidine-induced achlorhydria, corresponds to the pH-dependent in vitro dissolution properties of the products.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3225770&dopt=Abstract ranitidine






Digestion. 1988;40(1):25-32.
Comparison of the gastric antisecretory and antiulcer potencies of telenzepine, pirenzepine, ranitidine and cimetidine in the rat.

Riedel R, Bohnenkamp W, Eltze M, Heintze K, Prinz W, Kromer W.

Department of Pharmacology, Byk Gulden Research Laboratories, Konstanz, FRG.

In different rat models, the antisecretory and antiulcer effects of the M1-antimuscarinics telenzepine and pirenzepine, the nonselective antimuscarinic atropine, and the H2-blockers ranitidine and cimetidine were compared to each other. Intravenous telenzepine proved to be more potent in inhibiting gastric acid secretion in the Ghosh-Schild rat (carbachol-stimulated), the chronic fistula rat (basal secretion), or, both intravenously and orally, in the modified Shay rat, as compared to pirenzepine, cimetidine or ranitidine. After intravenous administration, only atropine was equally potent to telenzepine in all three models, but it was less potent than telenzepine after oral administration in the modified Shay rat. Gastric mucosal lesions induced by pylorus ligation plus acetylsalicyclic acid or acetylsalicyclic acid plus HCl were best inhibited by telenzepine and atropine, with pirenzepine, ranitidine and cimetidine being less potent, their relative potencies depending on the particular experimental model used. Thus, among the antiulcer drugs tested, telenzepine was the most potent one with respect to both antisecretory and antiulcer activity. Moreover, the duration of the antiulcer effect of telenzepine proved to be significantly longer than that of pirenzepine in the modified Shay rat.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3234616&dopt=Abstract ranitidine






Eur J Clin Pharmacol. 1989;37(3):305-7.
Plasma concentrations of pituitary and peripheral hormones during ranitidine treatment for two years in men with duodenal ulcer.

Knigge U, Thuesen B, Dejgaard A, Bennett P, Christiansen PM.

Department of Surgical Gastroenterology, Hvidovre Hospital, University of Copenhagen, Denmark.

The effects of treatment for 2 years with the histamine H2-receptor antagonist ranitidine (100 or 200 mg b.d. for 6 weeks followed by 100 or 200 mg daily) on plasma concentrations of pituitary and peripheral hormones in ten men with duodenal ulcer have been investigated. Stimulation tests with TRH 200 micrograms i.v. and LHRH 100 micrograms i.v. were performed before, during (6 and 24 months), and at least 6 months after treatment. Basal and TRH-stimulated prolactin (PRL) secretion was marginally reduced after treatment for 6 months, but not for 24 months. The LH response to LHRH was slightly increased after treatment for 6 months and 24 months and after the end of treatment. The plasma concentrations of TSH, FSH, cortisol, androgenic hormones, and thyroid hormones did not change significantly during treatment. No adverse effects were reported during the observation period. The few, minor changes in pituitary hormone concentrations were all within the reference range. They may be related to ranitidine treatment, but are more likely to be due to age-dependent alterations in hormone secretion. It is concluded that long-term treatment with ranitidine does not cause major changes in circulating hormone concentrations.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2515063&dopt=Abstract ranitidine






J Clin Pharmacol. 1988 Dec;28(12):1081-5.
Ranitidine accumulation in patients undergoing chronic hemodialysis.

Comstock TJ, Sica DA, Stone S, Davis J, Garnett WR, Karnes HT, Warner CW.

Department of Pharmacy and Pharmaceutics, Medical College of Virginia, Richmond.

Ranitidine accumulation was assessed in 20 patients undergoing chronic hemodialysis following oral daily doses of 150 mg ranitidine for 10 days. Serum ranitidine concentrations prior to dialysis were 191 +/- 115 mcg/l and 207 +/- 172 mcg/l for patients dialyzed three and two times per week, respectively. The amount of ranitidine recovered in the dialysate during the final dialysis session of the study was negligible and ranged from 308-3036 mcg, representing less than 3% of the administered dose. Clearance by hemodialysis was 3.0 +/- 1.1 l/hr. Once daily dosing of 150 mg ranitidine does not result in excessive accumulation, and drug loss during hemodialysis is small. These data suggest that supplemental dosing after hemodialysis is not indicated.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3243923&dopt=Abstract ranitidine






Arch Int Pharmacodyn Ther. 1988 Sep-Oct;295:245-56.
Effect of metoclopramide and ranitidine on acetylcholine release from isolated rat stomach.

Yoshida N, Karasawa T, Kadokawa T.

Department of Pharmacology, Dainippon Pharmaceutical Co., Ltd., Suita/Osaka, Japan.

Metoclopramide and ranitidine (10(-6)-10(-4) M) enhanced the electrical field stimulation-evoked contractions of isolated rat fundus and increased the gastric emptying in conscious rats. The enhancement of the fundus contractions by metoclopramide and ranitidine was abolished by atropine, but not by yohimbine, hexamethonium, propranolol or methysergide. The electrical field stimulation-evoked [3H]outflow from rat fundus strips, which has been preincubated with [3H]choline, was reduced by tetrodotoxin (10(-6) M) or in calcium-free medium, and potentiated by 4-amino-pyridine (3 X 10(-4) M), an acetylcholine (ACh)-releasing agent. Metoclopramide and ranitidine (10(-6)-10(-4) M) did not increase the [3H]outflow from the strips, in spite of causing a significant enhancement of their contractile response. However, both agents caused an increase in the ratio of [3H]acetylcholine/[3H]choline released into the superfusate during electrical field-stimulation. In rat fundus homogenates, metoclopramide and ranitidine showed a significant cholinesterase inhibition. These results seem to cast a doubt on the generally held ACh release hypothesis for the action mechanism of metoclopramide on one hand, and suggest, on the other hand, that cholinesterase inhibition contributes to some extent to the gastrokinetic effects of metoclopramide and ranitidine.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3245740&dopt=Abstract ranitidine






J Pharmacol Exp Ther. 1988 Feb;244(2):734-9.
Pharmacokinetic drug interactions between triamterene and ranitidine in humans: alterations in renal and hepatic clearances and gastrointestinal absorption.

Muirhead M, Bochner F, Somogyi A.

Department of Clinical and Experimental Pharmacology, University of Adelaide, Australia.

Ranitidine reduces the renal tubular secretion of the organic cations procainamide and N-acetylprocainamide in humans through competition for transport via the organic cation transport system. Ranitidine is thought to spare phase I hepatic metabolism mediated by cytochrome P-450, unlike its counterpart H2-receptor antagonist cimetidine. The aim of the present study was to determine, in eight human subjects, the effect of ranitidine on the disposition of the potassium-sparing diuretic triamterene, which undergoes renal tubular secretion, hepatic hydroxylation and subsequent sulphate conjugation to a pharmacologically active metabolite. Multiple blood and urine samples were collected throughout a dosing interval after chronic administration of triamterene alone, ranitidine alone or the two in combination. Ranitidine significantly (P less than .05) reduced the renal clearances of triamterene (51%) and p-hydroxytriamterene sulphate conjugate (47%), the clearance by hydroxylation of triamterene (30%) and the apparent absorption of triamterene (52%). In turn, triamterene reduced the renal clearance of ranitidine (14%). The interaction resulted in a small attenuation of the pharmacodynamic response to triamterene. These results necessitate consideration of the underlying mechanisms of the interactions and fall outside of our present understanding of the renal clearance of sulphate conjugates and the metabolic inhibitory effects of ranitidine. Competition for translocation across membranes is postulated as a common mechanism for the observed renal and hepatic interactions.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3346844&dopt=Abstract ranitidine






Cancer Chemother Pharmacol. 1988;21(4):323-8.
The influence of ranitidine on the pharmacokinetics and toxicity of doxorubicin in rabbits.

Harris NL, Brenner DE, Anthony LB, Collins JC, Halter S, Hande KR.

Department of Medicine, Nashville Veterans Administration Medical Center, TN 37203.

The influence of ranitidine on the pharmacokinetics and toxicity of doxorubicin was studied in six female New Zealand white rabbits. Plasma pharmacokinetic data were first obtained from rabbits given 3 mg/kg doxorubicin. After 1 month, the same rabbits were treated with ranitidine, 2.5 mg/kg or 25 mg/kg, before and during doxorubicin administration. The plasma doxorubicin assays to determine pharmacokinetic parameters were repeated. Drug toxicity was evaluated using complete blood counts, and hepatic function was measured using a 14C-aminopyrine breath test. High-dose ranitidine increased the total exposure to doxorubicin (area under the curve of doxorubicin alone = 1.44 +/- 0.88 microM.h/ml vs 4.49 +/- 2.35 microM.hr/ml for doxorubicin given with high-dose ranitidine; P = 0.06). Low-dose ranitidine did not alter doxorubicin pharmacokinetics. Exposure to doxorubicinol was altered by either high-dose or low-dose ranitidine. 14C-Aminopyrine half-life was altered by a ranitidine dose of 25 mg/kg (aminopyrine half-life after placebo control = 97 +/- 6 min as against aminopyrine half-life after ranitidine = 121 +/- 7 min; mean +/- SEM; P less than 0.02). Low-dose ranitidine did not exacerbate doxorubicin-induced myelosuppression. High-dose ranitidine enhanced doxorubicin-induced erythroid suppression while sparing the myeloid series. At cytochrome P-450-inhibitory doses, ranitidine's effects upon doxorubicin plasma pharmacokinetics are similar to those previously seen with cimetidine. These changes did not appear to alter drug detoxification and are not related to microsomal inhibition of doxorubicin detoxification. Low doses of ranitidine do not alter doxorubicin plasma pharmacokinetics or toxicity in rabbits.




Clin Pharmacol Ther. 1988 Jun;43(6):673-80.
Effect of cimetidine or ranitidine administration on nifedipine pharmacokinetics and pharmacodynamics.

Schwartz JB, Upton RA, Lin ET, Williams RL, Benet LZ.

Department of Pharmacy, University of California, San Francisco 94143.

The effect of cimetidine or ranitidine administration on responses to single and multiple doses of nifedipine were studied in 11 subjects who received cimetidine (300 mg q.i.d.) and 12 who received ranitidine (150 mg b.i.d.) in combination with nifedipine. After single doses of nifedipine, cimetidine decreased apparent oral clearance (dose/AUC) from 66 +/- 32 L/hr to 33 +/- 14 L/hr (p less than 0.01); elimination half-life increased from 4.0 +/- 2.2 to 4.9 +/- 2.9 hours (p less than 0.07). Increases in heart rate were greater (26 +/- 13 vs 13 +/- 11 beats/min standing; 19 +/- 11 vs 9 +/- 9 beats/min supine) and lasted longer than after nifedipine alone. Hypotensive effects were similar (10 +/- 7 mm Hg decrease vs 9 +/- 9 mm Hg). During nifedipine multiple-dose administration, cimetidine decreased the apparent oral clearance from 76 +/- 39 to 43 +/- 20 L/hr (p less than 0.01). Blood pressure responses were not altered by cimetidine but heart rate increased more (18 +/- 9 vs 9 +/- 9 beats/min supine; 18 +/- 13 vs 13 +/- 14 beats/min standing). Ranitidine coadministration did not alter nifedipine elimination or dynamic responses. During administration of nifedipine alone, the ratio of oral clearances (multiple to single doses) was 1.1 +/- 0.5. Thus (1) cimetidine but not ranitidine alters responses to nifedipine and (2) nifedipine kinetics do not differ between single- vs multiple-dose conditions.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3378388&dopt=Abstract ranitidine