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Medical research on zantac
Drug Saf. 2008; 31(7): 627-36
Estborn L, Joelson S
BACKGROUND: A potential causal association between an increase in gastric pH and a risk of community-acquired respiratory tract infection (RTI), specifically pneumonia, has been debated in relation to the use of potent gastric acid-suppressive medication. OBJECTIVE: To investigate the occurrence of community-acquired RTI, including pneumonia, in patients receiving esomeprazole versus placebo and other acid-suppressive agents in randomized clinical trials. METHODS: The AstraZeneca ARIADNE safety database was searched for comparative, controlled phase II-IV randomized, blinded clinical studies with esomeprazole and standard reporting of all adverse events (AEs). Pooled AE data were presented according to treatment comparison (esomeprazole versus placebo, esomeprazole 40 mg versus 20 mg daily, esomeprazole versus omeprazole, lansoprazole and/or ranitidine, respectively). Frequency and relative risk (RR), with 99% confidence interval (CI) and adjustment for time on treatment, were calculated for the following four AE categories: all RTIs; signs and symptoms potentially indicating RTI; lower RTI; and pneumonia. RESULTS: Thirty-one studies were identified, in which 16 583 patients received esomeprazole and 12 044 patients received either placebo or comparator acid-suppressive drugs. The occurrence of all four categories of AEs was similar between esomeprazole and placebo (all RTIs: 9.2% versus 8.5%; signs and symptoms of RTI: 1.8% versus 1.8%; lower RTI: 1.6% versus 1.5%; and pneumonia: 0.2% in both groups). The RR estimates were as follows: all RTIs, 0.93 (99% CI 0.78, 1.11); signs and symptoms of RTI, 0.85 (99% CI 0.57, 1.27); lower RTI, 0.92 (99% CI 0.59, 1.42); and pneumonia, 0.94 (99% CI 0.29, 3.07). The distribution of RTIs by patient sex and age showed a similar pattern in esomeprazole and placebo-treated patients. The comparisons of esomeprazole with the other comparator acid-suppressive drugs showed a similar pattern with only minor numerical differences in the occurrence of RTI between the drugs. There were no significant between-group differences with esomeprazole versus placebo for all four categories of AEs according to esomeprazole dosage, treatment indication and duration of treatment. CONCLUSIONS: This pooled analysis found no causal association between acid-suppressive therapy with esomeprazole and increased risk of community-acquired RTI, including pneumonia, in patients receiving this agent for gastric acid-related disorders.
J Sep Sci. 2008 Jun 11;
Pedrouzo M, Borrull F, Marcé RM, Pocurull E
This paper describes a method for determining 11 pharmaceuticals in various water sources by SPE followed by LC-(ESI) MS. SPE was carried out with Oasis(TM) HLB and the recoveries were 33-67% for 250 and 100 mL sewage water, 55-77% for 500 mL river water and 72-98% for 1 L tap water, with the exception of sulfamethoxazole and omeprazole which showed lower recoveries in all kinds of sample. The LODs in river water were of 5 ng/L for sulfadiazine, trimethoprim, sulfamethazine, sulfamethoxazole, and ranitidine and 10 ng/L for the other compounds. The highest concentrations found in river waters were for sulfamethoxazole (50 ng/L). In influent sewage waters, ranitidine was the most commonly detected compound with a maximum value of 0.24 mug/L.
Oral Morphine Overdose in a Cancer Patient Antagonized by Prolonged Naloxone Infusion.
Am J Hosp Palliat Care. 2008 Jun 6;
Upadhyay S, Jain R, Chauhan H, Gupta D, Mishra S, Bhatnagar S
An 80-year-old male was diagnosed with carcinoma in the lung with multiple bony metastases and had been prescribed pain medications as per World Health Organization analgesic ladder guidelines. However, he was not getting adequate pain relief and there were difficulties in titration of the morphine doses on an outpatient basis. Therefore, he was hospitalized for dose titration of oral morphine and was coprescribed amitriptyline and ranitidine. During the titration of the analgesic dose, he developed severe symptoms of morphine overdose. He was immediately treated with intravenous naloxone. After prolonged infusion of naloxone, he achieved his baseline vital parameters without any permanent sequel to the overdose event. This case report describes the possible causes of oral morphine overdose in the elderly and its successful treatment. To prevent such complications, one has to be very cautious of other factors such as drug interactions, particularly in the elderly.
Mcgill J Med. 2006 Jul; 9(2): 126-33
Lamichhane D, Giri B, Pathak O, Panta O, Shankar P
BACKGROUND: Recent studies on prescribing among outpatients in hospitals in Western Nepal are lacking. The main objectives of the study were to obtain information on the morbidity pattern among outpatients and to analyze prescribing using drug use indicators. METHODS: A retrospective hospital record based study from 01.01.2004 to 31.12.2004 was carried out among individuals attending the outpatient department (OPD) of the Manipal Teaching hospital, Pokhara, Western Nepal. A total of 32,017 new patients attended the OPD during the study period. Systematic random sampling (1 in every 20 patients) was done and 1600 patients selected. After excluding patients visiting the emergency department, those who got admitted and whose records were not available, 1261 cases were analyzed. The demographic details, morbidity pattern, average number of drugs prescribed, percentage of drugs prescribed by generic names and from the Essential drug list of Nepal (Essential drugs are those which satisfy the priority healthcare needs of the population), percentage of encounters with an antibiotic and an injection prescribed were noted. RESULTS: 1261 patients made 1772 visits. Upper respiratory tract infection and acid peptic disease were the most common diagnoses. The mean number of drugs was 1.99. Only 19.5% and 39.6% of drugs were prescribed by generic name and from the Essential drug list. Antibiotics and injections were prescribed in 26.4% and 0.96% of encounters. Cetrizine, vitamins, amoxicillin, the combination of paracetamol and ibuprofen and ranitidine were most commonly prescribed. CONCLUSIONS: Upper respiratory tract infections and acid peptic disease were the common illnesses. Generic prescribing and use of essential drugs were low. Some of the drug combinations being used were irrational. Prescriber education may be helpful in encouraging rational prescribing.
Anticholinergic Activity of 107 Medications Commonly Used by Older Adults.
J Am Geriatr Soc. 2008 May 26;
Chew ML, Mulsant BH, Pollock BG, Lehman ME, Greenspan A, Mahmoud RA, Kirshner MA, Sorisio DA, Bies RR, Gharabawi G
The objective of this study was to measure the anticholinergic activity (AA) of medications commonly used by older adults. A radioreceptor assay was used to investigate the AA of 107 medications. Six clinically relevant concentrations were assessed for each medication. Rodent forebrain and striatum homogenate was used with tritiated quinuclidinyl benzilate. Drug-free serum was added to medication and atropine standard-curve samples. For medications that showed detectable AA, average steady-state peak plasma and serum concentrations (C(max)) in older adults were used to estimate relationships between in vitro dose and AA. All results are reported in pmol/mL of atropine equivalents. At typical doses administered to older adults, amitriptyline, atropine, clozapine, dicyclomine, doxepin, L-hyoscyamine, thioridazine, and tolterodine demonstrated AA exceeding 15 pmol/mL. Chlorpromazine, diphenhydramine, nortriptyline, olanzapine, oxybutynin, and paroxetine had AA values of 5 to 15 pmol/mL. Citalopram, escitalopram, fluoxetine, lithium, mirtazapine, quetiapine, ranitidine, and temazepam had values less than 5 pmol/mL. Amoxicillin, celecoxib, cephalexin, diazepam, digoxin, diphenoxylate, donepezil, duloxetine, fentanyl, furosemide, hydrocodone, lansoprazole, levofloxacin, metformin, phenytoin, propoxyphene, and topiramate demonstrated AA only at the highest concentrations tested (patients with above-average C(max) values, who receive higher doses, or are frail may show AA). The remainder of the medications investigated did not demonstrate any AA at the concentrations examined. Psychotropic medications were particularly likely to demonstrate AA. Each of the drug classifications investigated (e.g., antipsychotic, cardiovascular) had at least one medication that demonstrated AA at therapeutic doses. Clinicians can use this information when choosing between equally efficacious medications, as well as in assessing overall anticholinergic burden.
Modification of sterculia gum with methacrylic acid to prepare a novel drug delivery system.
Int J Biol Macromol. 2008 Apr 16;
Singh B, Sharma N
The present paper deals with the modification of the sterculia gum with methacrylic acid (MAAc) to hydrogels for use in drug delivery. The hydrogels were characterized by SEMs, FTIR and swelling studies. The release dynamics of model anti-ulcer drug (ranitidine hydrochloride) from the hydrogels has been studied for the evaluation of the release mechanism. The values of the diffusion exponent 'n' (0.55, 0.54 and 0.59) and gel characteristic constant 'k' (2.109x10(-2), 3.698x10(-2) and 2.427x10(-2)) have been obtained, respectively, in distilled water, pH 2.2 buffer and pH 7.4 buffer. The release of the drug from the hydrogels occurred through non-Fickian diffusion mechanism.
Erythema multiforme associated with prophylactic use of phenytoin during cranial radiation therapy.
Am J Health Syst Pharm. 2008 Jun 1; 65(11): 1048-50
Barbosa LA, Teixeira CR
PURPOSE: A case of erythema multiforme associated with prophylactic use of phenytoin during cranial radiation therapy is reported. SUMMARY: A 60-year-old woman with intraductal adenocarcinoma of the breast and cerebral metastasis who had an implanted central venous catheter arrived at the hospital for the treatment of cerebral metastasis. She underwent whole brain irradiation and was given a total dose of 3750 cGy over 15 fractional doses spaced over three weeks. At the beginning of cranial radiation therapy, prophylactic oral ranitidine, oral dexamethasone, and oral phenytoin were initiated to prevent seizures. After 30 days of continuous prophylactic phenytoin and cranial radiation therapy, the patient developed an episode of coughing with yellow sputum, mucositis, and a minor skin reaction that was diagnosed in the emergency department as radiotherapy-associated lesions. After 2 days, the patient returned to the hospital with severe mucositis and an erythematous macular eruption on the scalp and auricular region within the radiation field. These were believed to be due to the radiation therapy, and the patient was subsequently hospitalized. The eruption dramatically extended over the next day, with itching micropapular urticarial lesions over large areas of the face, trunk, and genital region. The condition had worsened by the next day, with erythematous eruptions on the whole body (including the extremities), skin detachment, and vesicular lesions on the eyelids. The patient was then diagnosed toxic epidermal necrolysis. CONCLUSION: A patient with intraductal adenocarcinoma of the breast and cerebral metastasis developed erythema multiforme after receiving concurrent phenytoin and radiation therapy.
Ann R Coll Surg Engl. 2008 May; 90(4): 332-5
Madhusudhan TR, Rangan A, Gregg PJ
INTRODUCTION: Upper gastrointestinal (GI) bleeding in patients who undergo hip and knee arthroplasty tends to be associated with non-steroidal anti-inflammatory drug use, steroid intake, pre-existing peptic ulcers and smoking. The use of aspirin for thromboprophylaxis is an added risk for the occurrence of GI bleed. The aim of this study was to determine the incidence of upper GI bleeding and whether the use of peri-operative oral ranitidine reduces the incidence of upper GI bleeding when aspirin thromboprophylaxis is used for hip and knee arthroplasty. PATIENTS AND METHODS: Data from 1491 and 886 patients who underwent hip and knee replacements at the James Cook University Hospital (group 1) and at Friarage Hospital, Northallerton (group 2), respectively, were analysed in retrospect. All patients received 150 mg of aspirin per day for a period of 6 weeks from the day of surgery. Additionally, patients operated at the Friarage Hospital received 300 mg of oral ranitidine per day, for three postoperative days. RESULTS: We observed that patients in group 1 had a higher incidence of overt upper GI haemorrhage, which was statistically significant (P
Br J Clin Pharmacol. 2008 May 19;
Schöller-Gyüre M, Kakuda TN, De Smedt G, Vanaken H, Bouche MP, Peeters M, Woodfall B, Hoetelmans RM
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT * Drug-drug interactions with acid-suppressing agents were previously described with several other antiretroviral drugs. * Etravirine (TMC125) is a next-generation non-nucleoside reverse transcriptase inhibitor, metabolized by CYP3A and CYP2C enzymes with demonstrated efficacy in treatment-experienced HIV-infected patients. * The effect of acid-suppressing agents on the pharmacokinetics of etravirine was unknown. WHAT THIS STUDY ADDS * No clinically relevant effect was shown on the pharmacokinetics of etravirine when co-administered with ranitidine or omeprazole, drugs that increase gastric pH. * A drug-drug interaction due to CYP2C19 inhibition by omeprazole has been identified. * Etravirine can be co-administered with proton pump inhibitors and H(2) antagonists without dose adjustments. Aims Etravirine is a next-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) with activity against wild-type and NNRTI-resistant HIV. Proton pump inhibitors and H(2)-antagonists are frequently used in the HIV-negative-infected population, and drug-drug interactions have been described with other antiretrovirals. This study evaluated the effect of steady-state omeprazole and ranitidine on the pharmacokinetics of a single dose of etravirine. Methods In an open-label, randomized, one-way, three-period crossover trial, HIV-negative volunteers randomly received a single dose of 100 mg etravirine alone (treatment A); 11 days of 150 mg ranitidine b.i.d. (treatment B); and 11 days of 40 mg omeprazole q.d. (treatment C). A single dose of 100 mg etravirine was co-administered on day 8 of sessions 2 and 3. Each session was separated by a 14-day wash-out. Results Nineteen volunteers (seven female) participated. When a single dose of etravirine was administered in the presence of steady-state ranitidine, etravirine least squares means ratios (90% confidence interval) for AUC(last) and C(max) were 0.86 (0.76, 0.97) and 0.94 (0.75, 1.17), respectively, compared with administration of etravirine alone. When administered with steady-state omeprazole, these values were 1.41 (1.22, 1.62) and 1.17 (0.96, 1.43), respectively. Co-administration of a single dose of etravirine and ranitidine or omeprazole was generally safe and well tolerated. Conclusions Ranitidine slightly decreased etravirine exposure, whereas omeprazole increased it by approximately 41%. The increased exposure of etravirine when co-administered with omeprazole is attributed to CYP2C19 inhibition. Considering the favourable safety profile of etravirine, these changes are not clinically relevant. Etravirine can be co-administered with proton pump inhibitors and H(2) antagonists without dose adjustments.
Am J Physiol Gastrointest Liver Physiol. 2008 May 15;
Chew CS, Chen X, Bollag RJ, Isales CM, Ding KH, Zhang H
Lasp1 (LIM and SH3 domain protein1) is a multi-domain actin binding protein that is differentially expressed within epithelial tissues and brain. In the gastric mucosa, Lasp1 is highly expressed in the HCl-secreting parietal cell, where it is prominently localized within the F-actin rich subcellular regions. Histamine-induced elevation of parietal cell [cAMP]i increases Lasp1 phosphorylation, which is correlated with activation of HCl secretion. To determine if Lasp1 is involved in the regulation of HCl secretion in vivo, we generated a murine model with a targeted disruption of the Lasp1 gene. Lasp1-null mice had slightly lower body weights, but developed normally and had no overt phenotypic abnormalities. Basal HCl secretion was unaffected by loss of Lasp1, but histamine stimulation induced a more robust acid secretory response in Lasp1 null mice as compared to wild type littermates. A similar effect of histamine was observed in isolated gastric glands based on measurements of accumulation the weak base, [(14)C]-aminopyrine (AP). In addition, inhibition of the acid secretory response to histamine by H2 receptor blockade with ranitidine proceeded more slowly in glands from Lasp1 null mice. These findings support the conclusion that Lasp1 is involved in the regulation of parietal HCl secretion. We speculate that cAMP-dependent phosphorylation of Lasp1 alters interactions with F-actin and/or endocytic proteins that interact with Lasp1, thereby regulating the trafficking/activation of the H(+), K(+)-ATPase (proton pump). Key words: LIM and SH3 domain protein, [(14)C]-aminopyrine, transmission electron microscopy, bone mineral density.