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PubMed1996

[Hereditary factors in tumors of the digestive system].

Gastrointestinal tumours are an excellent model for the investigation of hereditary factors in cancer. Epidemiological studies on high risk population (China, Iran) evidenced a strong familiarity for esophageal cancer with up to 60% of the affected patients reporting a positive familiary history. About 10-15% of gastric cancer patients show a positive familiary history for this neoplasm. The proportion is even higher for the "diffuse" hystological type. Gastric cancer belongs to the neoplastic spectrum of hereditary nonpolyposis colorectal cancer, a genetic disease with an autosomal dominant pattern of inheritance. Familial polyposis coli and hereditary nonpolyposis colorectal cancer are the two main hereditary colon cancer syndromes. Familiar aggregation have been observed in about 10% of colorectal cancer cases. As for pancreatic cancer, anedoctal reports and one case control study have shown an increased risk of pancreatic carcinoma in patients with a positive family history both for all cancers (relative risk, RR, 2), and specific for pancreatic cancer (RR: 5).

Biomarkers, Tumor↗
PubMed2001

Long-term stability characterization of a controlled release gastrointestinal therapeutic system coated with a cellulose acetate pseudolatex.

The objective of the present study was to study the long term effects of storage of osmotically controlled gastrointestinal therapeutic system (GITS) in exaggerated conditions of temperature and humidity. Bilayered osmotic tablets were obtained with atenolol, Polyox N80, Carbopol 934P and magnesium stearate in one layer, and Polyox 303, Carbopol 974, sodium chloride and magnesium stearate in the other layer. A customized cellulose acetate (CA) pseudolatex was used to provide semipermeable housing around the tablet and an orifice was drilled into the drug layer to obtain the Atenolol GITS. The GITS were stored at 4 degrees C (refrigeration), 25 degrees C, 37 degrees C, 45 degrees C, 55 degrees C, 37 degrees C/11% RH, 37 degrees C/51% RH, and 37 degrees C/91% RH. Quantitative X-ray diffraction and dissolution studies were performed at regular intervals for one year. Aqueous CA polymeric film formation continued in GITS stored at higher temperature by gradual evaporation of moisture and coalescence of polymer. At lower temperatures atenolol crystallinity increased with time, but at higher temperatures the crystallinity was decreased. At higher humidity, a decrease in crystallinity was observed. A decrease in dissolution rate and extent was observed at higher temperature and higher humidity conditions. Exaggerated temperature and humidity conditions affected the dissolution profile by modifying the CA pseudolatex membrane and crystallinity of atenolol.

Adrenergic beta-Antagonists↗
PubMed1990

Nifedipine gastrointestinal therapeutic system in the treatment of hypertension. Results of a multicenter trial. The Modern Approach to the Treatment of Hypertension (MATH) Study Group.

Nifedipine, in the gastrointestinal therapeutic system (GITS) formulation, a controlled-release formulation for once-a-day administration, was evaluated in the Modern Approach to the Treatment of Hypertension (MATH) trial. In this study conducted at 127 centers, 1155 patients with mild-to-moderate hypertension representative of the spectrum seen in practice were included in the analyses of effectiveness. After a 2 week placebo period, nifedipine GITS therapy was started at 30 mg/day and was titrated to a maximum dose of 180 mg/day over 6 weeks. Response criteria were a sitting diastolic blood pressure less than 90 mm Hg and a decrease of greater than or equal to 10 mm Hg. After titration, patients were observed for 12 weeks during treatment. At the final visit, nifedipine GITS significantly (P less than .0001) reduced sitting systolic blood pressure 17 +/- 14 mm Hg (mean +/- SD), and sitting diastolic blood pressure 14 +/- 8 mm Hg. Similar highly significant reductions in standing blood pressure were observed. For all subjects, 76% achieved goal blood pressure response during titration. More than 50% were controlled on doses of 30 to 60 mg/day. At the final visit blood pressure reductions in men and women were similar, except for a significantly greater decrease in sitting systolic pressure for women. A similar proportion of blacks responded compared with whites, and reductions in sitting systolic and diastolic blood pressure were also similar in the 2 groups. Nifedipine GITS had no effect on renal function, serum potassium, or total, HDL, or LDL cholesterol. Uric acid was reduced by 0.5 mg/dL (P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2005

A double-blind placebo-controlled study evaluating the onset of action of doxazosin gastrointestinal therapeutic system in the treatment of benign prostatic hyperplasia.

OBJECTIVE: To determine the onset of improvement in benign prostatic hyperplasia symptoms in patients after treatment with doxazosin gastrointestinal therapeutic system (DOX GITS) versus placebo. METHODS: In this prospective, randomized, double-blind, placebo-controlled trial, baseline values, including International Prostate Symptom Score (IPSS) and maximum urine flow rate (Q(max)), were determined following a 2-week placebo run-in. Patients received DOX GITS 4 mg/d (n = 108) or placebo (n = 105) for 14 days. IPSS was measured on Days 3, 7, and 14; Q(max) on Days 1, 3, 7, and 14; and the patients' perception of improvement was measured on Days 1 and 2 in the evening at home and in the office on Day 14. RESULTS: Significantly more patients treated with DOX GITS than placebo perceived improvement after Day 1 (60.6% vs. 41.9%) through Day 14 (84.3% vs. 64.1%). On Day 1, improvement in Q(max) with DOX GITS was not significantly different compared with placebo. On Day 3 of the trial (1) IPSS improvement was significantly greater with DOX GITS than with placebo; (2) proportion of patients with > or =30% improvement in IPSS was significantly greater with DOX GITS (49.5%) than placebo (28.4%) and remained so through Day 14; (3) improvement in Q(max) was significantly greater with DOX GITS (3.7 mL/s) than placebo (1.9 mL/s) and remained so through Day 14; (4) proportion of patients with > or =3 mL/s increase in Q(max) was statistically greater with DOX GITS (54.4%) versus placebo (30.8%) and remained so through Day 14. CONCLUSIONS: DOX GITS significantly improved IPSS and Q(max) by Day 3 of treatment, and these changes were maintained through Day 14. More patients receiving DOX GITS than placebo perceived improvement in symptoms as early as Day 1.

Adrenergic alpha-Antagonists↗
PubMed2006

Long-term follow-up study to evaluate the efficacy and safety of the doxazosin gastrointestinal therapeutic system in patients with benign prostatic hyperplasia with or without concomitant hypertension.

OBJECTIVE: To assess the long-term efficacy and safety of extended-release doxazosin gastrointestinal therapeutic system (GITS) under routine clinical care conditions over 12 months in Korean men with benign prostatic hyperplasia (BPH) with and without coexisting hypertension. PATIENTS AND METHODS: In this open-label, multicentre, uncontrolled, flexible-dose study, 475 men (> or =40 years old) with clinical evidence of BPH were enrolled from 40 centres. Patients were evaluated at baseline and at 1, 2, 6 and 12 months of treatment. The primary efficacy variable was the Clinicians Global Assessment of Change (CGAC; improved, no change, or worse). Secondary efficacy variables were International Prostate Symptom Score (IPSS), quality of life (QoL), maximum urinary flow rate (Q(max)), and postvoid residual (PVR) urine volume. Adverse events (AEs) and blood pressure (BP) were also recorded. RESULTS: In all, 186 patients completed the study; based on the CGAC, most patients (155, 83.8%) improved and 31 (16.2%) had no change in symptoms. The mean (sd) change in the IPSS and QoL from baseline were -9.0 (6.8) and -1.6 (1.4), respectively (both P < 0.05). The Q(max) and PVR urine volume were significantly better than at baseline, with means of 10.5 (4.3) vs 13.7 (6.3), and 39.1 (37.0) vs 23.2 (33.7); P < 0.05). The decrease in systolic BP (SBP) and diastolic BP (DBP) from baseline in 52 hypertensive patients was significantly greater than in 134 normotensive patients, at (SBP/DBP) -9.5 (18.4)/-13.4 (10.9) vs -3.3 (12.5)/-1.4 (9.5); P < 0.05). A total of 47 AEs were reported in 41 of 475 patients (8.6%); the most common were dizziness (2.7%), erectile dysfunction (1.1%), dry mouth (1.1%), prostatic disorder (0.6%), and postural hypotension (0.4%). CONCLUSIONS: After 12 months, treatment with doxazosin GITS resulted in an improvement in > 83% of patients based on the CGAC, with significant improvements in IPSS, QoL, Q(max,) and PVR urine volume. Doxazosin GITS was effective and well tolerated as long-term therapy for Korean patients with BPH.

Adult↗
PubMed1981

The early detection of the effects of surgical shock on the viscera.

One hundred and one patients, in shock after operations were reviewed to examine the visceral effects on their prognoses. The shock was caused in 65 cases by hypovolaemia and in 36 cases by sepsis. The effects were studied on the heart and cardiovascular system, liver, kidneys, gastrointestinal system, central nervous system, lungs and blood clotting system. Surgical shock affected more frequently the lung and liver (P less than 0.05 and P less than 0.01). The lungs were most frequently involved in hypovolaemia (25 patients) and sepsis (25 cases). Pathology of the lung was associated with the highest mortality rate (P less than 0.005), followed by kidney (P less than 0.01) then heart and central nervous system (P less than 0.025). Involvement of the gastrointestinal tract or clotting system alone was not associated with higher mortality rates, except in the presence of other visceral derangements. Lung affection also had a greater mortality followed by kidney and the central nervous system. Involvement of one or several organs in failure to survive septic shock is dealt with in the discussion. It is concluded that visceral involvement secondary to shock could be of importance for prognosis.

Adolescent↗
PubMed2001

Ontogeny of neurohormonal peptides, serotonin, and nitric oxide synthase in the gastrointestinal neuroendocrine system of the axolotl (Ambystoma mexicanum): an immunohistochemical analysis.

The ontogeny of the neurohormonal peptides vasoactive intestinal polypeptide (VIP), neurotensin (NT), substance P (SP), calcitonin gene-related peptide (CGRP), gastrin/cholecystokinin (GAS/CCK), and somatostatin (SOM) as well as serotonin (SER) and nitric oxide synthase (NOS) was investigated in the gastrointestinal tract of the urodele Ambystoma mexicanum, the axolotl, using immunohistochemical techniques. The first regulatory substances to appear were SP, SOM, and SER that could be immunohistochemically detected up from stage 1. At early stage 2, VIP immunoreactivity was observed infrequently in enteric nerve fibers. With the onset of external feeding at late stage 2, SP-immunoreactive (IR) and SER-IR endocrine cells and VIP-IR nerve fibers were present throughout the gastrointestinal tract. Furthermore, in the small intestine NT-IR and GAS/CCK-IR endocrine cells appeared. At stage 3, SER immunoreactivity was observed not only in endocrine cells but also in nerve fibers. CGRP-IR and SP-IR nerve fibers were detectable at stage 4 and stage 5, respectively. From stage 5 on, a minority of the CGRP immunoreactivity occurred in SP-IR nerve fibers. NOS immunoreactivity did not appear before stage 6 when it was found infrequently in nerve fibers. Thus, several phases of development can be distinguished: (1) at the yolk sac stages only few regulatory substances are present. (2) At the onset of external feeding, all endocrine cell types investigated were readily detectable. Thus, the onset of external feeding seems to trigger the development of the gastrointestinal endocrine system. (3) The endocrine cells are first found in the proximal part of the gastrointestinal tract and later in higher numbers in the distal parts. (4) The dually distributed neurohormonal peptides and SER first appear in endocrine cells and later additionally in nerve fibers. Thus, the nerve fibers likely set up the fine regulation of gastrointestinal blood flow and motility.

Ambystoma↗
PubMed1991

Effect of food on bioavailability of pseudoephedrine and brompheniramine administered from a gastrointestinal therapeutic system.

The purpose of this study was to determine how a high-fat meal affects the delivery and absorption of pseudoephedrine and brompheniramine maleate when delivered from a gastrointestinal therapeutic system (GITS). This study was a randomized, complete crossover trial with 12 healthy male volunteers who were given single doses of the 24-h GITS under fed and fasted conditions. Pharmacokinetic parameters for both drugs were comparable between fed and fasted treatments, except for a shorter time to maximum concentration of pseudoephedrine for fed subjects (p = 0.002). Bioavailability of pseudoephedrine was 91% for fed relative to fasted treatment; for brompheniramine it was 89%. These results indicate that codelivery of the two drugs from the GITS is reliable and prolonged, and that the resulting absorption of pseudoephedrine and brompheniramine is minimally affected by food.

Adult↗
PubMed1999

A short-term cost-of-treatment model for type 2 diabetes: comparison of glipizide gastrointestinal therapeutic system, metformin, and acarbose.

OBJECTIVE: To compare, from a managed care perspective, the 3-year costs of 3 first-line monotherapy strategies in type 2 diabetes patients: glipizide gastrointestinal therapeutic system (GITS), metformin, and acarbose. STUDY DESIGN: A Markov model, with a Monte Carlo simulation, was developed to compare the costs to achieve full glycemic control (hemoglobin A1c of < or = 7%) with each first-line strategy. PATIENTS AND METHODS: The patient population for the model was assumed to be all newly diagnosed type 2 diabetes patients eligible for monotherapy with an oral agent. Each monotherapy could be succeeded by add-on treatments. The model included the costs of routine medical care and supplies, medication, adverse events, and treatment failures. RESULTS: Using a Monte Carlo simulation, the mean 3-year cumulative costs per patient were $4971, $5273, and $5311 for glipizide GITS, metformin, and acarbose first-line strategies, respectively. The main cost drivers were drug prices. Mean 3-year cost savings for first-line glipizide GITS were $301 over metformin and $340 over acarbose. Between 83% and 85% of all simulations showed cost savings with glipizide GITS compared with the other agents. CONCLUSIONS: The model suggests first-line monotherapy with glipizide GITS should result in desirable short-term economic benefits for managed care. Because the model incorporates recommended glycemic goals and performed well in sensitivity analyses, it should be applicable to a variety of clinical practices and useful for economic assessments of new therapies. Results of this model should be verified prospectively in typical care settings.

Acarbose↗
PubMed1998

Aqueous-based polymeric dispersion: face-centered cubic design for the development of atenolol gastrointestinal therapeutic system.

The main objective of the study was to use the statistical response surface methodology to evaluate the effect of formulation variables and their interaction on drug release in atenolol gastrointestinal therapeutic system (GITS) development coated with cellulose acetate (CA) pseudolatex system. A three-factor, three-level, face-centered design was employed to evaluate the quadratic response surface, and to achieve the desired response in atenolol delivery. Coating was achieved by spraying plasticized CA pseudolatex on atenolol bilayered tablets in a Uni-Glatt fluidized-bed coater. The independent variables were orifice size (X1), percent coating weight gain (X2) and Carbopol 934P (X3). The response variable (Y1) was time for 50% (t50%) drug dissolution with a constraint on cumulative percent released in 24 hr (Y2). The polynomial equation obtained was Y1 = 61.88 - 3779.8X1 + 1.89X2 - 3.95X3 - 266.87 X1X2 - 1675X1X3 + 0.07X2X3 + 215123X1(2) + 0.06X2(2) + 0.10X3(2). Contour and response plots were used to relate the independent and dependent variables. The optimization procedure predicted a t50% of 10.83 hr with 92% atenolol release in 24 hr when orifice size (X1), percent coating weight gain (X2), and Carbopol 934P (X3) were 0.014 in., 13%, and 20 mg, respectively. Preparation and testing of optimized formulation showed a good correlation between the predicted and observed values.

Adrenergic beta-Antagonists↗
PubMed1987

Nifedipine gastrointestinal therapeutic system in stable angina pectoris. Results of a multicenter open-label crossover comparison with standard nifedipine.

To compare the clinical efficacy and dose equivalency of standard nifedipine versus a new gastrointestinal therapeutic system (GITS) formulation of nifedipine, 98 patients with chronic stable angina pectoris participated in a 14-week, multicenter, open-label, crossover trial. All patients were administered nifedipine capsules for one month prior to study entry and continued receiving other antianginal, non-calcium blocker medications. Ninety-one patients (93 percent), 80 men and 11 women, mean age 62 +/- 1 years, completed the trial, which included two weeks receiving standard nifedipine followed by 12 weeks receiving nifedipine GITS starting at a dosage equal to the 24-hour total dose of nifedipine capsules and titrated upward as necessary. However, throughout the trial, mean nifedipine dosage was similar on nifedipine GITS compared with standard nifedipine. Angina frequency was significantly less with nifedipine GITS at Weeks 6, 10, and 14 (0.8 episodes/week) compared with baseline with standard nifedipine (1.3 episodes/week, p less than 0.05). Likewise, nitroglycerin consumption was also less at Weeks 6, 10, and 14, but only significantly less at Week 6 (nifedipine 1.2/week versus nifedipine GITS at six weeks, 0.7/week; p less than 0.05). Resting hemodynamic parameters, including systolic and diastolic blood pressure and heart rate, were not significantly different with standard nifedipine versus nifedipine GITS during the 12-week study. Total incidences of side effects were similar for both treatments (standard nifedipine, 16; nifedipine GITS, 17). However, incidence of vasodilator side effects (flushing, dizziness, and light-headedness) was significantly less frequent with nifedipine GITS (standard nifedipine, 12; nifedipine GITS, six; p less than 0.05). Thus, results from this open-label, crossover trial suggest that nifedipine GITS dosing is similar to multidose standard nifedipine with equivalent 24-hour efficacy for nifedipine GITS.

Aged↗
PubMed2001

A combined analysis of double-blind trials of the efficacy and tolerability of doxazosin-gastrointestinal therapeutic system, doxazosin standard and placebo in patients with benign prostatic hyperplasia.

OBJECTIVE: To report an integrated analysis of two previous studies fully characterizing the clinical utility of the controlled-release gastrointestinal therapeutic system (GITS) formulation of doxazosin in the treatment of benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: Two pivotal randomized, double-blind studies of doxazosin GITS for BPH were assessed by an integrated analysis. Both studies included a 2-week washout period, a 2-week single-blind placebo run-in phase, and a 13-week double-blind treatment phase. One study compared doxazosin GITS, doxazosin standard (-S) and placebo in 795 men; the other compared doxazosin GITS and doxazosin-S in 680 men. Doxazosin GITS was initiated at 4 mg once daily and titrated to 8 mg once daily after 7 weeks, and doxazosin-S was initiated at 1 mg once daily and titrated to a maximum of 8 mg once daily over 7 weeks as needed to achieve optimal symptom control. The primary outcome measures were mean changes from baseline to the final visit for the International Prostate Symptom Score (IPSS) and maximum urinary flow rate (Qmax) in the per-protocol population. Numerous symptom- and urinary-related secondary outcomes were assessed, as were effects of therapy on male erectile dysfunction measured using the International Index of Erectile Function (IIEF) in one study. RESULTS: Both doxazosin GITS and doxazosin-S significantly improved the symptoms of BPH, as shown by a 45% reduction for each in total IPSS from baseline to final visit, compared with a 34% reduction in patients on placebo. Doxazosin GITS and doxazosin-S produced comparable improvements in Qmax that were significantly greater than with placebo, with a greater improvement sooner after treatment with doxazosin GITS than with doxazosin-S. Nearly half of the patients on doxazosin GITS had symptom relief at the 4-mg starting dose. A similar number of patients in both doxazosin groups were titrated to the maximum dose. Secondary outcomes were consistent with the primary effects. Both doxazosin GITS and doxazosin-S produced significant improvements in sexual function according to IIEF scores among those with dysfunction at baseline. The overall incidence of adverse events was similar among patients treated with doxazosin GITS and placebo, and slightly lower than those on doxazosin-S. There was no apparent difference in the type of adverse events reported for the two formulations of doxazosin, although most adverse events were reported at a lower frequency with doxazosin GITS. CONCLUSION: Doxazosin GITS is significantly more effective than placebo in reducing the clinical symptoms of BPH and improving Qmax, and as effective as doxazosin-S. Both doxazosin formulations improved sexual function in patients with BPH and sexual dysfunction at baseline. Doxazosin GITS produced a therapeutic effect equivalent to that of doxazosin-S, but with fewer titration steps and a slightly lower overall incidence of adverse events.

Adrenergic alpha-Antagonists↗
PubMed1991

Assessment of quality of life by patient and spouse during antihypertensive therapy with atenolol and nifedipine gastrointestinal therapeutic system.

To evaluate differences in efficacy, safety, and quality of life, 394 male patients with mild-to-moderate hypertension were randomized to receive 20 weeks of either atenolol or nifedipine gastrointestinal therapeutic system (GITS) in a multicenter double-blind trial. A four-week placebo washout was followed by 8 weeks of titration and 12 weeks of maintenance therapy. Quality-of-life evaluation included clinical assessments by the patient and parallel take-home assessments by patient and spouse. Blood pressure was controlled equally in both groups. The total incidence of adverse reactions was similar in both groups, but a greater percentage of nifedipine GITS patients withdrew due to peripheral edema. Patients completing 20 weeks of therapy demonstrated a more favorable quality-of-life profile (P less than .05) for nifedipine GITS over atenolol in psychosocial (P less than .01), well-being (P less than .05), general affect (P less than .05), emotional ties (P less than .01), emotional control (P less than .05), vitality (P less than .05), and leisure (P less than .05) scores. Treatment differences were particularly pronounced for patients over 50 years of age and were not fully detectable until after 14 weeks of therapy. Deterioration in quality of life was associated with withdrawal. Spouses of younger patients receiving atenolol reported deterioration in sexual satisfaction as compared to spouses of patients taking nifedipine GITS (P less than .02). Thus age, length of trial, and third-party observation are important factors in quality-of-life assessment. Comparison of adverse reactions provides an incomplete measure of how well a drug is tolerated. In contrast, findings indicate that even subtle CNS-mediated effects on mood and well-being can be detected by quality-of-life evaluation.

Adult↗
PubMed1995

Influence of non-steroidal anti-inflammatory drugs on renal function and 24h ambulatory blood pressure-reducing effects of enalapril and nifedipine gastrointestinal therapeutic system in hypertensive patients.

OBJECTIVE: To evaluate the influence of non-steroidal anti-inflammatory drugs (NSAIDs; aspirin and indomethacin) on the renal and antihypertensive effects of enalapril and nifedipine gastrointestinal therapeutic system (GITS) in patients with essential hypertension. DESIGN AND METHODS: In a crossover study, 18 patients on an unrestricted-salt diet were randomly assigned to receive either enalapril (20-40 mg/day) or nifedipine-GITS (30-60 mg/day) for 4-8 weeks, followed by aspirin (100 mg/day for 2 weeks) and then indomethacin (75 mg/day for 1 week). Blood pressure was measured by 24h ambulatory monitoring. RESULTS: Enalapril and nifedipine-GITS significantly reduced blood pressure compared with placebo. Aspirin did not alter the antihypertensive effect of either drug. Indomethacin attenuated (by 45%) the antihypertensive effect of enalapril throughout the 24h period of evaluation, but did not interfere with the effect of nifedipine. Furthermore, indomethacin significantly reduced the fractional excretion of sodium and plasma levels of prostaglandins in a similar way when added to either the enalapril or the nifedipine regimen. CONCLUSIONS: Vasodilatory prostaglandins are probably involved in the antihypertensive effects of enalapril but not of nifedipine, and this interaction seems to be independent of any indomethacin-induced decrease in renal sodium excretion. Nifedipine may be an appropriate drug to treat hypertensive patients requiring concomitant therapy with NSAID.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1996

The nifedipine gastrointestinal therapeutic system (GITS). Evaluation of pharmaceutical, pharmacokinetic and pharmacological properties.

Nifedipine is a short-acting calcium antagonist formulated into several different oral preparations, each of which offers a distinct drug release profile. Of these, the nifedipine gastrointestinal therapeutic system (GITS) affords (rate)-controlled-release (CR) and once-daily administration. Although it is recognised that CR drug formulations may enhance the treatment compliance of patients by reducing the number of daily doses, there are several pharmaceutical, pharmacokinetic and pharmacological considerations which may influence the ultimate selection of a particular dosage form. The formulation design of the nifedipine GITS involves an osmotic pump process which provides approximately zero-order delivery of the drug. This mechanism serves to prevent the possibility of dose dumping, but more importantly allows for maintenance of the relatively constant plasma drug concentrations assumed necessary to maintain smooth control of blood pressure. The pharmacokinetic characteristics of the nifedipine GITS have been evaluated in both single- and multiple-dose studies. The GITS formulation provides drug concentrations which reach a plateau within 6 hours after administration of a single dose, and continue at that concentration until at least 24 hours after administration. In this way large fluctuations in plasma drug concentrations are avoided, which may improve the efficacy and tolerability of the drug. Although a trend showing a small increase in the 24-hour plasma nifedipine concentrations has been observed by our group from some single-dose studies, it does not appear to be clinically relevant. One potentially important disadvantage of the GITS compared with 'naturally' long-acting agents is that the 'intrinsic' pharmacokinetic properties of nifedipine may be exposed in poorly compliant patients, leading to extended periods of subtherapeutic drug concentrations. Drug delivery by the nifedipine GITS is unaffected by changes in pH and gastrointestinal (GI) motility, but the rate of drug release can increase slightly with food intake (although absolute bioavailability remains unchanged). No studies have been conducted to determine the average GI transit time of this particular dosage form, but it is possible that inadequate retention may occur in some patients, perhaps leading to less optimal clinical outcomes. For example, the median GI transit time for both oxprenolol and metoprolol Oros drug delivery systems has been reported as 27.4 hours, with individual times ranging from 5.1 to 58.3 hours. The possibility of inadequate GI retention of the nifedipine GITS is perhaps more likely in patients who have pre-existing GI motility disorders or who are taking other medications that enhance GI motility. The interaction between grapefruit juice and nifedipine is interesting, considering that the exact mechanism involved has yet to be determined. Nonetheless, inhibition of presystemic metabolic processes (probably involving liver enzymes but possibly also enzymes contained within the wall of the small intestine) is likely to be a factor in the increased bioavailability of nifedipine observed in individuals coingesting grapefruit juice. Thus, potential nifedipine formulation differences with respect to the degree of interaction with grapefruit juice may occur if a significant degree of extrahepatic metabolism is involved. The majority of clinical trials with the nifedipine GITS have assessed its efficacy in patients with mild-to-moderate essential hypertension, and have found it to be at least equivalent to other dosage forms of the drug. Since there is limited information available directly comparing the efficacy and adverse effects of the different types of nifedipine formulation, little attention has been focused on this subject. However, modifying the rate and duration of nifedipine release may profoundly affect the clinical performance of this drug. A slower rate of intravenous nifedipine infusion has been shown to reduce the incide

Animals↗
PubMedDate not supplied

Nifedipine gastrointestinal therapeutic system versus nifedipine coat-core: comparison of efficacy via 24-hour ambulatory blood pressure monitoring.

OBJECTIVE: To assess the comparable efficacy and adverse effect profile of two extended-release preparations of nifedipine--gastrointestinal therapeutic system (GITS) and coat-core (CC)--in patients with mild-to-moderate hypertension. DESIGN: Single institution, single-blind, prospective study. SETTING: Dwight David Eisenhower Army Medical Center, Fort Gordon, GA. PATIENTS: Ninety-one patients who were taking nifedipine GITS as a sole antihypertensive agent were randomized to receive either GITS or CC. After 3 weeks, 24-hour ambulatory blood pressure monitoring was conducted and an adverse effect questionnaire was administered. The patients were then crossed over to the other treatment arm and monitoring was repeated after 3 weeks. MEASUREMENTS: Mean blood pressure, heart rates, and the percentage of readings exceeding 140 mm Hg systolic and 90 mm Hg diastolic were compared for the 24-hour period. Additionally, mean blood pressures at 4-hour intervals after drug administration and heart rate during the first 8 hours of the dosage interval were compared. RESULTS: Ninety-one patients enrolled, 79 completed the study, and 62 patients were included in the efficacy analysis. A statistically significant difference (p = 0.020) was shown only in the last 4-hour systolic blood pressure. However, this difference was small (122 +/- 15 mm Hg with GITS vs. 126 +/- 14 mm Hg with CC). There was no difference in the percentage of readings exceeding 140 mm Hg systolic or 90 mm Hg diastolic. Neither dosage nor treatment order had an effect on the results. Adverse effects were reported with a greater frequency during CC therapy (40 with CC vs. 22 with GITS; p = 0.006), but were generally transient. Discontinuation of the drug was necessary in 3 patients during the CC cycle. CONCLUSIONS: GITS and CC demonstrated clinically equivalent antihypertensive efficacy in the study population. The CC produce may have a higher rate of adverse effects, but drug discontinuation was uncommon.

Adult↗
PubMed2002

The non-H pylori helicobacters: their expanding role in gastrointestinal and systemic diseases.

The number of species in the genus Helicobacter has rapidly expanded over the past decade. The genus now includes at least 24 formally named species as well as numerous other helicobacters awaiting formal naming. This review highlights the expanding role that other helicobacters, although not as well known as H pylori, play in gastrointestinal and systemic disease in humans.

Arthritis, Infectious↗
PubMedDate not supplied

Comparative effects of lercanidipine, lacidipine, and nifedipine gastrointestinal therapeutic system on blood pressure and heart rate in elderly hypertensive patients: the ELderly and LErcanidipine (ELLE) study.

This study was conducted to compare the antihypertensive efficacy and safety of lercanidipine with those of lacidipine and nifedipine gastrointestinal therapeutic systems in patients aged 65 years or above with mild-to-moderate hypertension. Patients were randomized to receive lercanidipine 5 mg, lacidipine 2 mg, or nifedipine 30 mg for 24 weeks. After 2 weeks, the dose was doubled in non-responding patients. At 24 weeks, blood pressure was significantly reduced in the three treatment groups. The decrease in systolic blood pressure was similar in all three groups. The decrease in diastolic blood pressure in the lercanidipine group (-18.3 mmHg) was comparable to that in the nifedipine group (-17.7 mmHg), but exceeded that in the lacidipine group (-16.6 mmHg). The incidence of adverse drug reactions (ADRs) was lowest in the lercanidipine group (19.4%) compared with the nifedipine group (28.4%) and the lacidipine group (27.1%). In particular, edema was least frequent in the lercanidipine group (2.8%) compared with the lacidipine group (7.5%) and the nifedipine group (10.1%). These data demonstrate that lercanidipine is effective in lowering blood pressure in older adult hypertensive patients while maintaining a superior tolerability and safety profile.

Aged↗