Loratadine (SCH29851) 40 mg once daily versus terfenadine 60 mg twice daily in the treatment of seasonal allergic rhinitis

Seventy patients received loratadine 40 mg once daily, terfenadine 60 mg twice daily, or placebo in a 14-day, double-blind, randomized study. Four nasal and four non-nasal symptoms associated with allergic rhinitis were evaluated. At the endpoint (the last evaluable visit), the mean total scores of combined nasal and non-nasal symptoms decreased (improved) from the baseline by 51.8% and 55.7% with loratadine and terfenadine, respectively, but increased (worsened) by 6.1% with placebo. There was a significant difference between both the loratadine and terfenadine treatment groups and the placebo group (P = 0.001) but not between the active medication groups (P = 0.608). Overall therapeutic response was good or excellent in 14 of the 23 patients given loratadine, in 18 of the 24 given terfenadine and in none of the 23 given placebo. The difference between each active medication group and the placebo group was significant (P less than or equal to 0.01) but there was no significant difference between the two active treatment groups (P greater than 0.35). No loratadine patient had any adverse side-effects. Sedating effects occurred in one terfenadine patient, headache in one placebo patient and two terfenadine patients (one terfenadine patient with severe headache discontinued treatment), and dyspepsia in two placebo patients. No anti-cholinergic effects occurred in this study. Loratadine 40 mg once daily was effective and safe in the relief of symptoms of allergic rhinitis.     

Multi-centre double-blind comparison of terfenadine once daily versus twice daily in patients with hay fever

This double-blind, randomized multi-centre study was designed to compare efficacy and tolerability of 120 mg terfenadine taken once daily (in the morning) with the established regimen of 60 mg terfenadine taken twice daily in the treatment of seasonal rhinitis. Two comparable groups, a total of 191 hay fever patients, were treated for 1 week. Symptom severity was assessed by the investigators before and at the end of the treatment (visual analogue scale), and daily by the patient (four-point rating scale). All symptoms improved to a similar degree in both groups. Differences between the two groups were not statistically significant, except for nasal symptoms in three cases as assessed by the visual analogue scale in one centre (better relief in the group given 120 mg terfenadine once daily). Tolerability was good and similar in both groups. The data presented show that in the treatment of hay fever 120 mg terfenadine given once daily is an effective, convenient and well tolerated alternative to the regimen of 60 mg terfenadine given twice daily.     

Comparative efficacy of once versus twice daily mevinolin in the therapy of familial hypercholesterolemia

Mevinolin, a competitive inhibitor of the rate-limiting enzyme in cholesterol biosynthesis, is an effective hypocholesterolemic agent in patients with primary hypercholesterolemia when given in a twice-daily regimen. The present study compares the hypocholesterolemic effects of mevinolin given in a twice-daily dosage regimen with the same total dosage given either once in the morning or once in the evening in 12 patients with heterozygous familial hypercholesterolemia. Ten patients took a total daily dose of 40 mg of mevinolin and two took 20 mg. On the twice-daily dosage regimen, plasma concentrations of total cholesterol decreased 29.5% and 35.9% as compared with 21.4% and 26.9% with mevinolin given once in the morning and 27% and 32.2% with the drug given once in the evening. These values are all significantly different from baseline, but differences between the three treatment regimens do not reach statistical significance (P = 0.07 for the twice-daily versus once-in-the-morning dosage regimens). We conclude that once-daily administration of mevinolin, particularly in the evening, is an effective hypocholesterolemic regimen in patients with familial hypercholesterolemia.     

Comparative efficacy and safety of once-daily versus twice-daily loratadine-pseudoephedrine combinations versus placebo in seasonal allergic rhinitis

The objective of this study was to compare the efficacy and safety of Claritin-D 24 Hour (once daily) with that of Claritin-D 12 Hour (twice daily) and placebo in the treatment of patients with seasonal allergic rhinitis (SAR). In this double-blind, placebo-controlled, multicenter study, 469 patients with moderate-to-severe SAR symptoms were treated for 2 weeks with one of the following: Claritin-D 24 Hour (a combination tablet formulation of loratadine 10 mg in the coating and pseudoephedrine sulfate 240 mg in an extended-release core), Claritin-D 12 Hour (a combination tablet formulation of loratadine 5 mg in the tablet coating and 120 mg pseudoephedrine sulfate, 60 mg in the coating and 60 mg in the core), or placebo. Claritin-D 24 Hour and Claritin-D 12 Hour were consistently superior to placebo (P < 0.01) in reducing total, nasal, and nonnasal symptom scores. Patients in the Claritin-D 24 Hour and Claritin-D 12 Hour groups also had significantly greater (P 相似文献   

Treatment of seasonal allergic rhinitis with flunisolide and terfenadine

A study of ninety-nine hay fever sufferers was conducted to compare the effect of treatment with flunisolide nasal spray plus terfenadine tablets with that of terfenadine alone. The study was carried out over an 11-week period, which covered the pollen season between May and August. All patients received 60 mg terfenadine twice daily and one group, of forty-nine patients, also received 50 mcg flunisolide to each nostril twice daily. Clinical assessments of nasal and ocular symptoms were made at admission and following 3, 7 and 11 weeks' treatment. An over-all evaluation of treatment effect was performed at each follow-up visit and nasal examination was carried out. Patients also completed diary cards daily. Both treatments were effective in reducing symptom severity, in comparison with previous seasons, but the combination treatment gave consistently better symptom relief. Statistically significant differences were detected in favour of the combined treatments group for nasal symptoms. Eye symptoms were found to be relieved to a comparable degree by both treatments. Results from daily patient self-assessments were consistent with these findings. The over-all evaluations by both patients and doctors were significantly in favour of flunisolide plus terfenadine. In conclusion, treatment of hay fever with flunisolide in addition to terfenadine was significantly more effective than treatment with the antihistamine alone.     

Onset of action of loratadine and placebo and other efficacy variables in patients with seasonal allergic rhinitis.

In a double-blind study, 185 patients with seasonal allergic rhinitis were randomly assigned to receive 10 mg of loratadine or placebo once daily for three days. On day 1 of treatment, the onset of relief of symptoms within 30 minutes of drug administration was reported by 13% of the loratadine-treated patients and by 4% of the placebo patients (P less than 0.05). At two hours after drug administration, 65% of the loratadine-treated patients and 48% of the placebo patients reported symptom relief. On day 3, the loratadine-treated patients reported a significantly greater relief of symptoms, and according to both physician and patient evaluations, the treatment response was significantly superior in the loratadine-treated than in the placebo patients. The incidence of sedation was 2% in the loratadine group and 1% in the placebo group.     

Nasal effect of cetirizine and loratadine at 24 hours in patients with allergic rhinitis

Numerous studies have compared the duration of the cutaneous effect of cetirizine and loratadine. We assessed their nasal effects 24 hours after administration in patients with allergic rhinitis, using a randomized, double-blind, crossover, placebo-controlled trial. Nasal challenge was performed by nebulization of increasing doubling dosages of histamine (0.04-1.28 mg/nostril) in 12 patients (seven males, five females, aged 31 +/- 7 years). Nasal airway resistance was measured by posterior rhinomanometry 24 hours after intake of cetirizine (10 mg), loratadine (10 mg), or placebo. Baseline nasal airway resistance was identical on all study days (2.86 +/- 0.10 cm H2 O/L per second). Twenty-four hours after intake, the dose-response curve of nasal obstruction to histamine was significantly lower after treatment with cetirizine compared with placebo (P < 0.05). However, although the curve was lower on loratadine than on placebo, the curves did not differ significantly. In conclusion, our study shows significant efficacy of cetirizine, but not of loratadine, in the nose at 24 hours after a single dose. This suggests that the nasal action of cetirizine is longer lasting than that of loratadine in patients with allergic rhinitis.     

Multicentre, double-blind comparison of terfenadine and cetirizine in patients with seasonal allergic rhinitis

This double-blind, multicentre study was designed to compare the efficacy and tolerability of terfenadine 120 mg with cetirizine 10 mg, each taken once daily, in the treatment of seasonal allergic rhinitis. Two hundred and eighty-five patients were recruited to the study by nine general practice centres in the south of England during the 1989 hay-fever season. Symptom severity was assessed daily by the patient and before and after the one-week treatment period by the investigator. At the second clinic visit both patient and investigator assessed the overall response to treatment. The two treatment groups were well matched for all demographic variables and baseline symptom scores. Improvement in all seven symptoms (nasal congestion, sneezing, rhinorrhoea, itching nose, itching eyes, watery eyes and red eyes) and overall response to treatment were similar in both treatment groups. Adverse events were mainly of mild to moderate severity and were reported by 14 patients on terfenadine and 21 patients treated with cetirizine (p = 0.317). This study confirmed terfenadine's role as the treatment of choice in hayfever. A single 120 mg dose in the morning effectively reduced symptoms by 43 to 70 per cent of baseline values, with an acceptably low incidence of side effects. Cetirizine at a single dose of 10 mg displayed equal efficacy in controlling hayfever symptoms but, in common with other studies, had a significantly greater incidence of drowsiness (p = 0.046).     

Comparative efficacy of perindopril and enalapril once daily using 24-hour ambulatory blood pressure monitoring

ACE inhibitors are important therapeutic agents in controlling hypertension, correcting some of its pathophysiological derangement and improving its prognosis. While there are many such agents, there may be some important differences between them. This placebo run-in, double blind, crossover study, using 24-hour ambulatory blood pressure monitoring, compares the efficacy of perindopril 4-8 mg and enalapril 10-20 mg as once daily antihypertensive agents on 32 patients. For diastolic blood pressure (DBP), perindopril had a placebo-corrected peak (P) reduction of blood pressure (BP) of -6.4 +/- 1.3 mmHg vs its placebo-corrected trough (T) of -5.2 +/- 1.7 mmHg. Enalapril had a reduction in DBP of -8.5 +/- 1.3 mmHg (P) and -5.7 +/- 1.7 mmHg (T). For systolic blood pressure (SBP), perindopril had a reduction of -7.5 +/- 1.6 mmHg (P) vs -7.3 +/- 2.2 mmHg (T) compared to enalapril with -10.8 +/- 1.6 mmHg (P) vs -8.3 +/- 2.3 mmHg (T). Placebo-corrected trough-to-peak ratio (SBP/DBP) for perindopril was 0.97/0.81 vs 0.77/0.67 for enalapril. There was no difference noted in 24-hour mean BP, area under the curve or post-dose casual BP measurements. Both perindopril and enalapril were well tolerated and the two treatment groups had similar safety profiles. Perindopril thus had a predictable and sustained blood pressure effect giving a 24-hour cover for the patient without excessive peak effect or poor trough effect.     

A comparison of tazarotene 0.1% gel once daily plus mometasone furoate 0.1% cream once daily versus calcipotriene 0.005% ointment twice daily in the treatment of plaque psoriasis

BACKGROUND: Both tazarotene (a retinoid prodrug) and calcipotriene (a synthetic analog of vitamin D3) are effective in the treatment of plaque psoriasis, but no reports in the literature directly compare the efficacy and tolerability of these 2 drugs. Tazarotene is commonly used in conjunction with a topical corticosteroid. In this study, tazarotene was used with mometasone furoate (a synthetic corticosteroid), and the 2-drug regimen was compared with calcipotriene monotherapy. OBJECTIVE: This study was conducted to compare the efficacy and tolerability of tazarotene 0.1% gel once daily plus mometasone furoate 0.1% cream once daily with those of calcipotriene 0.005% ointment twice daily in the treatment of plaque psoriasis. METHODS: In this multicenter, investigator-blinded, parallel-group study, adult patients with chronic, stable plaque psoriasis affecting 5% to 20% of their body surface area were randomly allocated to receive up to 8 weeks of treatment with either tazarotene 0.1% gel once daily (in the evening) plus mometasone furoate 0.1% cream once daily (in the morning) or calcipotriene 0.005% ointment twice daily. Patients were assessed at baseline and at weeks 2, 4, and 8 of treatment. Patients who demonstrated complete clearance of plaque psoriasis after 2 or 4 weeks of treatment and those whose psoriasis had improved > or = 50% after 8 weeks of treatment entered a 12-week posttreatment follow-up phase during which they applied only moisturizer. Patients were reassessed after 4, 8, and 12 weeks of posttreatment follow-up. Physician-rated measures of efficacy included global improvement, plaque elevation, scaling, erythema, and percentage of body surface area involvement. Patient-rated assessments included efficacy of study treatment compared with previous therapies, comfort of treated skin, outlook for long-term control of psoriasis, and overall impression of treatment. RESULTS: Of 120 patients with moderate to severe psoriasis enrolled from 3 centers, 106 (88%) completed the study. No significant differences in baseline clinical variables were observed between the 2 groups. Twenty-seven patients (45%) in the tazarotene plus cortico-steroid group achieved marked improvement (> or = 75% global improvement) after 2 weeks of treatment compared with 15 patients (26%) in the calcipotriene group (P < or = 0.05). Between-group comparisons of the percentage of patients achieving complete or almost complete clearance (> or = 90% global improvement) did not reach statistical significance at any time point. When compared with the calcipotriene regimen, the tazarotene plus corticosteroid regimen resulted in significantly greater efficacy on trunk lesions in reducing plaque elevation (at the end of treatment and at week 4 of the posttreatment phase, P < or = 0.05), scaling (week 4 of treatment and week 4 of the posttreatment phase, P < or = 0.05), erythema (week 4 of treatment and at the end of treatment, P < or = 0.05), and percentage of body surface area involvement (weeks 2 and 4 of treatment, P < or = 0.01). In addition, the tazarotene plus corticosteroid regimen was significantly more effective in reducing the percentage of body surface area involvement in upper limb lesions (weeks 2 [P < or = 0.05] and 4 [P < or = 0.01] of treatment). Forty-two of 55 patients (76%) in the tazarotene plus corticosteroid group rated their medication as more or much more effective than previous therapies compared with 30 of 52 patients (58%) in the calcipotriene group (P < or = 0.05). Although adverse events (burning, pruritus, irritation, and erythema) occurred in a significantly greater proportion of patients who received tazarotene plus corticosteroid than in those who received calcipotriene (P < or = 0.05), 47 of 55 patients (85%) in both groups rated the comfort of their treated skin as "somewhat comfortable" or better and both groups had similar discontinuation rates due to treatment-related adverse events (3% and 5%, respectively). CONCL     

Omalizumab for treatment of allergic rhinitis

Introduction: Immunoglobulin E (IgE) is a key pathogenic factor of allergic rhinitis, a prevalent disease adversely affecting quality of life and productivity.

Areas covered: Binding of inhaled allergens to IgE on the surface of basophils and mast cells, with subsequent cross-linkage of IgE and aggregation of high-affinity receptors for IgE (Fc?RI), triggers the release of inflammatory mediators, followed by the onset of allergic rhinitis symptoms. Current therapeutic strategies include corticosteroids, mast cell stabilizers, leukotriene receptor antagonists, anticholinergics, antihistamines and allergen immunotherapy. Removal of circulating free IgE by the recombinant humanized monoclonal anti-IgE antibody, omalizumab (Xolair), represents a novel therapeutic approach. Omalizumab selectively binds to the C?3 domain of IgE at the site of Fc?R1 binding, thus blocking binding of IgE to effector cells. We review omalizumab's clinical efficacy, administration, use with immunotherapy and safety in allergic rhinitis.

Expert opinion: Omalizumab may provide a new treatment strategy for allergic rhinitis. The high cost of omalizumab precludes its chronic use for allergic rhinitis and it is not FDA approved for this indication; however, its periodic use may be justified in treatment resistant patients, especially those with seasonal disease.     

Azatadine maleate/pseudoephedrine sulfate repetabs versus placebo in the treatment of severe seasonal allergic rhinitis

The symptoms of seasonal allergic rhinitis can be alleviated by the use of an antihistamine and a decongestant. The efficacy and safety of the combination of azatadine maleate and pseudoephedrine sulfate were examined in this double-blind study comparing active drug to placebo. While 74% of the patients administered the combination drug showed marked improvement in the signs and symptoms of seasonal allergic rhinitis, only 29% of patients receiving placebo demonstrated improvement. Adverse reactions were mild and transient.     

过敏性鼻炎的防治

1 过敏性鼻炎的定义及概况 过敏性鼻炎,也就是变态反应性鼻炎的俗称,它是过敏原通过呼吸道进入体内,主要与鼻腔黏膜发生过敏反应炎症而引发的鼻部慢性疾病.目前,随着工业化进程的加快和人们生活水平的提高,过敏性鼻炎的发病率逐年上升,目前已达正常人群的10%～20%左右.     

Clinical efficacy and safety of telmisartan 80 mg once daily vs. atenolol 50 mg once daily in patients with mild-to-moderate hypertension

The objective of this open-label, parallel-group comparative study was to assess the clinical efficacy and safety of once-daily treatment for 8 weeks with telmisartan 80 mg in comparison with atenolol 50 mg on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in patients with mild-to-moderate hypertension (morning supine SBP 141-199 mmHg, DBP 95-114 mmHg). A total of 58 patients were enrolled. The comparability of the two treatment groups was statistically documented at the beginning of the study. Telmisartan was more effective than atenolol, with a decrease in SBP of 21.7 mmHg vs. 11.8 mmHg (p = 0.03) and a non-significant decrease in DBP of 14.7 mmHg vs. 10.1 mmHg. The safety profiles of both drugs were very similar; both drugs were well tolerated. In conclusion, once-daily telmisartan 80 mg is more effective than once-daily atenolol 50 mg in lowering SBP with no negative chronotropism. Furthermore, telmisartan was as well tolerated as atenolol in the treatment of mild-to-moderate essential hypertension in adults.     

Intracellular pharmacokinetics of once versus twice daily zidovudine and lamivudine in adolescents

Zidovudine (ZDV) and lamivudine (3TC) metabolism to triphosphates (TP) is necessary for antiviral activity. The aims of this study were to compare ZDV-TP and 3TC-TP concentrations in adolescents receiving twice daily (BID) and once daily (QD) regimens and to determine the metabolite concentrations of ZDV and 3TC during chronic therapy on a QD regimen. Human immunodeficiency virus-infected patients (12 to 24 years) taking ZDV (600 mg/day) and 3TC (300 mg/day) as part of a highly active antiretroviral therapy regimen received QD and BID regimens of ZDV and 3TC for 7 to 14 days in a crossover design. Serial blood samples were obtained over 24 h on the QD regimen. Intracellular mono-, di-, and triphosphates for ZDV and 3TC were measured. The median ratio of BID/QD for ZDV-TP predose concentrations was 1.28 (95% confidence interval [CI] = 1.00 to 2.45) and for 3TC-TP was 1.12 (95% CI = 0.81 to 1.96). The typical population estimated half-lives (+/- the standard error of the mean) were 9.1 +/- 0.859 h for ZDV-TP and 17.7 +/- 2.8 h for 3TC-TP. Most patients had detectable levels of the TP of ZDV (24 of 27) and 3TC (24 of 25) 24 h after dosing, and half-lives on a QD regimen were similar to previously reported values when the drugs were given BID. Lower, but not significantly different, concentrations of ZDV-TP were demonstrated in the QD regimen compared to the BID regimen (P = 0.056). Although findings were similar between the BID and QD groups, the lower concentrations of ZDV and the number of patients below the level of detection after 24 h suggests that ZDV should continue to be administered BID.     

Darunavir/cobicistat once daily for the treatment of HIV

A current focus in HIV management is improving adherence by minimizing pill burden with convenient formulations, including fixed-dose combinations (FDCs). Darunavir, a HIV protease inhibitor, co-administered with low-dose ritonavir (800/100 mg once daily), is recommended in guidelines in combination with other antiretrovirals for HIV patients with no darunavir resistance-associated mutations. Cobicistat is an alternative agent to ritonavir for boosting plasma drug levels of darunavir among other antiretrovirals. Cobicistat is a more specific cytochrome P450 3A inhibitor than ritonavir without enzyme-inducing properties. This review describes the differing effects of cobicistat and ritonavir on metabolic enzymes, which explains their differing drug–drug interactions, and summarizes some of the studied drug–drug interactions for cobicistat. It also outlines the clinical development and data for a once-daily darunavir/cobicistat FDC. This FDC thus allows for a once-daily treatment regimen (including background antiretrovirals) with reduced pill burden.     

A study of amikacin given once versus twice daily in serious infections

Forty-five mostly elderly patients with serious infections were treated in a prospective, comparative and randomized pharmacokinetic study with amikacin 11.0 or 15.0 mg/kg administered in a single daily dose as an intravenous, short-term infusion or with amikacin 7.5 mg/kg administered twice daily in the same way. The results indicate that administration of amikacin 15 mg/kg in a single daily dose should be a practical and safe principle of administration. However elderly patients often have reduced creatinine clearance and should preferably be given a lower dose of 11 mg/kg bw. The risk of nephrotoxicity did not increase, but conclusions on ototoxicity and clinical efficacy cannot be drawn from this limited study. This should be considered as an initial part of a future multicentre trial.