Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thirty-six healthy male volunteers were enrolled in two sequential double-masked, placebo-controlled trials with the objective of assessing the safety and local tolerability of 2% cyclosporine ophthalmic ointment. Subjects were randomly assigned to active or placebo groups and dosed once, twice, or thrice daily for 14 days. Safety and tolerability were assessed through patient interviews, ophthalmologic examinations, routine laboratory testing, and blood cyclosporine assays. Relative to placebo, cyclosporine ointment was associated with higher frequencies of ocular burning, tearing, redness, itching, and headache. These intolerances were dose-related and reported predominantly in the TID group; QD and BID cyclosporine ophthalmic ointment were better tolerated than the placebo control. Symptoms were usually mild, were reported only once beyond Day 2 in the QD-BID groups, and never required interruption of the study. Transitory, asymptomatic, and unexplained elevations of serum transaminases were seen in five subjects in the first study, but were not confirmed in the second and are not felt to be drug-related. Cyclosporine blood levels were uniformly below the limits of detection. We conclude that the tolerability profile of 2% cyclosporine ointment, dosed once or twice daily in normal volunteers, is acceptable and supportive of trials in patient populations.
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PMID:Safety and tolerability of two percent cyclosporine (Sandimmune) ophthalmic ointment in normal volunteers. 180 90

An integrated analysis of the fifteen published prospective multicenter studies that have examined the safety and efficacy of famotidine for the short-term (13) and maintenance (2) therapy of duodenal ulcer included over 2,600 patients. The thirteen studies of endoscopically proved acute duodenal ulcer that were published in English or were available in a complete English translation were reviewed. Six of these studies compared famotidine with ranitidine, one with cimetidine, one with gefarnate, and one with placebo, and four were uncontrolled. In controlled studies of the short-term therapy of symptomatic duodenal ulcer, famotidine was equal in efficacy to ranitidine or cimetidine and superior to placebo and gefarnate at all times examined. The efficacy of famotidine was examined in three oral dosing regimens--20 mg BID, 40 mg HS, and 40 mg BID. There were no significant differences in efficacy or side effects associated with these three regimens. Overall, the cumulative healing rate with famotidine was 46% at two weeks, 77% at four weeks, and 91% at eight weeks. In studies involving 50 patients or more, famotidine 40 mg orally HS resulted in healing rates for active duodenal ulcer of 82% to 100% after four weeks. Adverse effects were uncommon with all dosages examined. Adverse effects led to the discontinuation of therapy in three patients--two owing to the development of rash and one because of dizziness. Headache and constipation were the most common adverse experiences, but in no study were the adverse experiences that were seen with famotidine significantly more frequent than those seen with ranitidine or placebo. No patient undergoing therapy for active duodenal ulcer had a biochemical abnormality that required a change in therapy or that was drug related in the opinion of the investigator. Multicenter studies examining the efficacy of famotidine in reducing the incidence of duodenal ulcer recurrence showed that famotidine was superior to placebo at all intervals examined. In conclusion, the data from the studies included in this review show that famotidine is highly effective and generally well tolerated both in the short-term treatment of active duodenal ulcer and in the maintenance therapy of duodenal ulcer.
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PMID:Famotidine in the management of duodenal ulcer: an analysis of multicenter findings worldwide. 307 11

Forty patients with irritable bowel syndrome were randomly allocated to treatment with octylonium bromide (20 mg TID) or cimetropium bromide (50 mg BID) in a double-blind trial lasting for six weeks. Drugs were taken before meals, according to a double-blind schedule. Clinical evaluations were made of digestive and other symptoms, objective findings (pain at palpation, contracted colon, tympanites), and overall effectiveness of treatment. Statistically significant decreases in severity of abdominal pain and subjective scores for bowel habits were obtained in both groups. The only statistically significant differences between treatments were in nondigestive symptoms (asthenia, palpitations, tremor, headache, etc.), which improved more in the cimetropium bromide group. No severe side effects were observed in either treatment group.
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PMID:Double-blind study of a new antimuscarinic, cimetropium bromide, in patients with irritable bowel syndrome. 352 59

This study compared the efficacy and tolerability of oral ondansetron (8 mg twice daily [BID] for up to 3 days) with those of phenothiazine prochlorperazine (10 mg BID for up to 3 days) in 133 cancer patients receiving cyclophosphamide-based chemotherapy. In addition, the study evaluated the impact of these treatments on patients' health-related quality of life, measured with both the Functional Living Index--Cancer and the Functional Living Index--Emesis questionnaires. The first dose of study drug was administered 30 minutes before initiation of chemotherapy. Patients received a rescue antiemetic at their request or if the investigator deemed it necessary. There was a statistically significant difference in the number of patients with no emetic episodes over the 3-day study period: 60% in the ondansetron group compared with 21% in the prochlorperazine group. Twenty-five percent of ondansetron-treated patients compared with 68% of prochlorperazine-treated patients experienced three or more emetic episodes, rescue medication use, or withdrawal from the study due to adverse events or lack of efficacy of the study drug. Among patients with at least one emetic episode, the mean time to emesis was significantly longer (13 hours and 37 minutes) in the ondansetron group compared with the prochlorperazine group (9 hours and 30 minutes). Nausea and appetite scores did not differ significantly between groups. The score on the vomiting subscale of the Functional Living Index--Emesis was significantly more favorable in the ondansetron group compared with the prochlorperazine group, indicating better maintenance of health-related quality of life in ondansetron-treated patients. Both treatments were well tolerated. The most common potentially drug-related adverse event was headache, which occurred in significantly more (16%) ondansetron-treated patients compared with prochlorperazine-treated patients (3%). The results of this study demonstrate that oral ondansetron 8 mg BID for up to 3 days is more effective than prochlorperazine 10 mg BID for up to 3 days in the prevention of emesis associated with moderately emetogenic chemotherapy.
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PMID:Efficacy and tolerability of oral ondansetron versus prochlorperazine in the prevention of emesis associated with cyclophosphamide-based chemotherapy and maintenance of health-related quality of life. 887 3

This study compared the efficacy and tolerability of oral ondansetron (8 mg twice daily [BID] for up to 3 days) with those of phenothiazine prochlorperazine (10 mg BID for up to 3 days) in 133 cancer patients receiving cyclophosphamide-based chemotherapy. In addition, the study evaluated the impact of these treatments on patients' health-related quality of life, measured with both the Functional Living Index-Cancer and the Functional Living Index-Emesis questionnaires. The first dose of study drug was administered 30 minutes before initiation of chemotherapy. Patients received a rescue antiemetic at their request or if the investigator deemed it necessary. There was a statistically significant difference in the number of patients with no emetic episodes over the 3-day study period: 60% in the ondansetron group compared with 21% in the prochlorperazine group. Twenty-five percent of ondansetron-treated patients compared with 68% of prochlorperazine-treated patients experienced three or more emetic episodes, rescue medication use, or withdrawal from the study due to emesis or adverse events. Among patients with at least one emetic episode, the mean time to emesis was significantly longer (13 hours and 37 minutes) in the ondansetron group compared with the prochlorperazine group (9 hours and 30 minutes). Nausea and appetite scores did not differ significantly between groups. The score on the vomiting subscale of the Functional Living Index-Emesis was significantly more favorable in the ondansetron group compared with the prochlorperazine group, indicating better maintenance of health-related quality of life in ondansetron-treated patients. Both treatments were well tolerated. The most common potentially drug-related adverse event was headache, which occurred in significantly more (16%) ondansetron-treated patients compared with prochlorperazine-treated patients (3%). The results of this study demonstrate that oral ondansetron 8 mg BID for up to 3 days is more effective than prochlorperazine 10 mg BID for up to 3 days in the prevention of emesis associated with moderately emetogenic chemotherapy.
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PMID:Efficacy and tolerability of oral ondansetron versus prochlorperazine in the prevention of emesis associated with cyclophosphamide-based chemotherapy and maintenance of health-related quality of life. 882 27

In a multicenter, community-based study involving more than 300 primary care physicians in the United States, the efficacy and safety of ciprofloxacin and clarithromycin were compared in the treatment of patients with complicated or severe acute bacterial exacerbations of chronic bronchitis (i.e., those who had failed previous antibiotic treatment within the prior 2 to 4 weeks; those with susceptibility data suggestive of a resistant pathogen; those having three or more acute exacerbations of chronic bronchitis [AECB] within the past year; and those having three or more comorbid conditions). Patients were randomized to either ciprofloxacin (CIP) 750 mg BID or clarithromycin (CLR) 500 mg BID, both administered for 10 days; all patients were treated on an outpatient basis. Clinical response at the end of therapy was the primary efficacy variable. An interim analysis was performed on the results from 743 patients (369 CIP, 374 CLR) with clinical and bacteriologic evidence of a bronchopulmonary infection who had completed an ongoing study as of the end of May 1997. Three hundred nine pathogens were isolated before therapy, including Haemophilus spp (75 isolates), Moraxella catarrhalis (67 isolates), Staphylococcus aureus (55 isolates), and Streptococcus pneumoniae (23 isolates). Seven hundred eighteen patients (97%) were included in the efficacy-valid population. Clinical success at the end of therapy was observed in 90% (272 of 302) and 88% (274 of 313) of efficacy-valid patients treated with CIP and CLR, respectively (95% confidence interval [CI] = -2.4 to 7.6). Corresponding rates for the intent-to-treat population were also 90% (283 of 314) and 88% (281 of 321), respectively (95% CI = -2.3 to 7.5). The bacteriologic response for efficacy-valid patients at the end of therapy was 98% (119 of 122) for CIP-treated and 93% (103 of 111) for CLR-treated patients (95% CI = -0.8 to 10.2). The eradication rates for the three most commonly isolated gram-negative pathogens were 100% for CIP-treated and 95% for CLR-treated patients and 96% each for the two most commonly isolated gram-positive organisms. Superinfections due to respiratory tract pathogens were more common in the CLR group (10 organisms) than in the CIP group (4 organisms). Seventy-four (20%) CIP-treated and 62 (17%) CLR-treated patients reported 118 and 103 respective study-emergent adverse events. Headache, abdominal pain, diarrhea, nausea, and vomiting in CIP-treated patients and diarrhea, nausea, vomiting, and taste perversion in CLR-treated patients were the most commonly reported adverse events. Treatment of patients with complicated or severe AECB with CIP 750 mg BID was associated with rates of clinical success and bacteriologic eradication similar to those with CLR.
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PMID:Efficacy of ciprofloxacin and clarithromycin in acute bacterial exacerbations of complicated chronic bronchitis: interim analysis. Bronchitis Study Group. 938 86

A multicenter, parallel-design, randomized, double-masked study was conducted to compare the efficacy and safety of 2% dorzolamide with those of 0.5% betaxolol in the treatment of elevated intraocular pressure (i.o.p). A total of 311 adults with ocular hypertension or open-angle glaucoma were randomly allocated to receive either 2% dorzolamide administered topically TID or 0.5% betaxolol administered topically BID plus placebo administered topically QD for 12 weeks. After the washout of previous ocular hypotensive drugs, patients with IOP > or = 23 mm Hg in at least one eye at 10 AM or 4 PM on study day 1 were randomly allocated to receive one of the study treatments. Throughout the study, IOP was measured 2 and 8 hours after instillation of study medication for the morning peak effect (hour 2) and afternoon trough effect (hour 8). After 12 weeks of therapy, the mean change in IOP was not significantly different between the dorzolamide and betaxolol treatment groups at hour 8 (-3.6 mm Hg in both groups) or hour 2 (-5.4 vs -5.3 mm Hg, respectively). The differences between treatments (and 95% CIs associated with these differences) in mean IOP changes from baseline were 0.02 mm Hg (-0.870 to 0.901) for hour 8 and -0.14 mm Hg (-0.959 to 0.685) for hour 2. The ocular adverse experience (AE) most frequently reported by patients was ocular burning and/or stinging, and the most frequently reported nonocular AEs were taste perversion, upper respiratory infection, and headache. Only the incidence of taste perversion was significantly different between treatment groups (14.6% for the dorzolamide group and 0.0% for the betaxolol group). Two percent of patients in each treatment group discontinued the study due to AEs. This study confirmed the similar IOP-lowering effect of 2% dorzolamide and 0.5% betaxolol. Both treatments were generally well tolerated, and their safety profiles were similar.
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PMID:Comparison of the efficacy and safety of 2% dorzolamide and 0.5% betaxolol in the treatment of elevated intraocular pressure. Dorzolamide Comparison Study Group. 966 61

Reduced cholinergic transmission is a key neurotransmitter dysfunction in Alzheimer's Disease (AD). NXX-066, a physostigmine analog and acetylcholinesterase (AChE) inhibitor, has demonstrated activity in animal models of memory function, and was well tolerated in healthy subjects up to a single dose of 64 mg and multiple doses of 60 mg QD for seven days. Since AChE inhibitors are often tolerated differently in AD patients than in healthy volunteers, a randomized, placebo-controlled, double-blind, single-center, inpatient bridging study was conducted to determine the maximum tolerated dose (MTD) of NXX-066 in the target patient population. Seven consecutive panels of eight AD patients each (6 active, 2 placebo) received fixed oral doses of NXX-066 (20, 30, 40, 50, 60, 70, or 80 mg BID) for seven days. Initiation of each subsequent panel (dose group) was contingent upon the tolerability of lower dose levels. The MTD was determined to be 70 mg BID when four of six patients receiving 80 mg BID were prematurely discontinued from the study due to nausea and/or vomiting, accompanied in some patients by mild to moderate dizziness, headache, asthenia, and gastric symptoms. Wide variability in plasma levels of NXX-066 was observed in all dose panels. AChE inhibition in whole blood correlated with both maximum plasma concentration and dose; however, AChE inhibition was not predictive of adverse events. In this study, AD patients tolerated larger daily doses of NXX-066 on a BID regimen than healthy normal subjects had tolerated with QD dosing. Further studies are warranted to examine whether differing tolerability between patients and healthy subjects or the reduced dosing interval explains these findings.
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PMID:NXX-066 in patients with Alzheimer's disease: a bridging study. 1021 Feb 64

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most frequently prescribed drugs, despite their well-established association with gastroduodenal injury. Recent discovery of the cyclooxygenase (COX) isoenzymes COX-1 and COX-2 has improved our knowledge of the action of NSAIDs. COX-1 is continuously expressed in almost all tissues, where it converts arachidonate to the prostaglandins (PGs) important in homeostatic function; COX-2 is present in immune cells, blood vessel endothelial cells, and synovial fibroblasts. Classic NSAIDs inhibit both COX isoenzymes by occupying the cyclooxygenase-active site, preventing access by arachidonic acid. In theory, a drug such as celecoxib that selectively inhibited COX-2 might block inflammation, pain, and fever while reducing the side effects (gastric erosions and ulcers) associated with inhibition of COX-1. In animal models of inflammation and pain, celecoxib has shown marked suppression of PG production and inflammation compared with indomethacin, the standard COX-1/COX-2 inhibitor. In clinical trials, celecoxib dosed at 100, 200, and 400 mg BID was found to significantly reduce the signs and symptoms of rheumatoid arthritis (RA) and osteoarthritis. In one RA study, celecoxib was found to be as clinically effective as diclofenac after 24 weeks of treatment; at the end of the study, gastroduodenal ulcers occurred significantly more frequently in the diclofenac group (15%) than in the celecoxib group (4%). In a 1-week endoscopy study comparing celecoxib with naproxen and placebo, the incidence of gastric erosions/ulcers was significantly greater in the naproxen group than in the celecoxib or placebo group. The most common adverse effects of celecoxib in clinical studies were headache, diarrhea, abdominal discomfort, and dizziness. Celecoxib has shown significant equivalent anti-inflammatory and analgesic efficacy and has produced less endoscopically apparent gastrointestinal (GI) ulceration or erosion than have 3 classic NSAIDs. Whether it will have long-term GI adverse effects or interact with other medications to cause serious adverse responses (eg, increased GI bleeding or rash in conjunction with other sulfonamide-like drugs) is unknown and remains to be established.
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PMID:Celecoxib, a selective cyclooxygenase-2 inhibitor for the treatment of rheumatoid arthritis and osteoarthritis. 1050 45

Abacavir (formerly 1592U89) is a carbocyclic nucleoside analog with potent anti-human immunodeficiency virus (anti-HIV) activity when administered alone or in combination with other antiretroviral agents. The population pharmacokinetics and pharmacodynamics of abacavir were investigated in 41 HIV type 1 (HIV-1)-infected, antiretroviral naive adults with baseline CD4(+) cell counts of >/=100/mm(3) and plasma HIV-1 RNA levels of >30,000 copies/ml. Data for analysis were obtained from patients who received randomized, blinded monotherapy with abacavir at 100, 300, or 600 mg twice-daily (BID) for up to 12 weeks. Plasma abacavir concentrations from sparse sampling were analyzed by standard population pharmacokinetic methods, and the effects of dose, combination therapy, gender, weight, and age on parameter estimates were investigated. Bayesian pharmacokinetic parameter estimates were calculated to determine the peak concentration of abacavir in plasma (C(max)) and the area under the concentration-time curve from time zero to infinity (AUC(0-infinity)) for individual subjects. The pharmacokinetics of abacavir were dose proportional over the 100- to 600-mg dose range and were unaffected by any covariates. No significant correlations were observed between the incidence of the five most common adverse events (headache, nausea, diarrhea, vomiting, and malaise or fatigue) and AUC(0-infinity). A significant correlation was observed between C(max) and nausea by categorical analysis (P = 0.019), but this was of borderline significance by logistic regression (odds ratio, 1.45; 95% confidence interval, 0.95 to 2.32). The log(10) time-averaged AUC(0-infinity) minus baseline (AAUCMB) values for HIV-1 RNA and CD4(+) cell count correlated significantly with C(max) and AUC(0-infinity), but with better model fits for AUC(0-infinity). The increase in AAUCMB values for CD4(+) cell count plateaued early for drug exposures that were associated with little change in AAUCMB values for plasma HIV-1 RNA. There was less than a 0.4 log(10) difference over 12 weeks in the HIV-1 RNA levels with the doubling of the abacavir AUC(0-infinity) from 300 to 600 mg BID dosing. In conclusion, pharmacodynamic modeling supports the selection of abacavir 300 mg twice-daily dosing.
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PMID:Population pharmacokinetics and pharmacodynamic modeling of abacavir (1592U89) from a dose-ranging, double-blind, randomized monotherapy trial with human immunodeficiency virus-infected subjects. 1089 75


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