Efficacy and Safety of Cerivastatin, 0.2 mg and 0.4 mg,in Patients with Primary Hypercholesterolemia: a Multinational,Randomised, Double-blind Study

Summary

Elevated serum cholesterol level is a key risk factor for cardiovascular morbidity and mortality. Cerivastatin is a highly effective lipid-lowering agent currently licensed at doses of 0.1, 0.2, 0.3 and 0.4?mg.

This was a multicentre, randomised, double-blind, parallel-group study comparing the efficacy and safety of cerivastatin OAmglday with that of cerivastatin 0.2?mg/day in patients with primary hypercholesterolemia. There was a six-week placebo run-in phase followed by a 24-week active treatment phase. A total of 494 patients were randomised to receive cerivastatin 0.4mg (n = 332) or 0.2mg (n = 162). Per-protocol (PP) analysis revealed that mean low-density lipoprotein cholesterol (LDL-C) level decreased by 38.4 ± 0.7% from baseline in the 0.4?mg group, compared with a decrease of 31.5 ± 0.9% in the 0.2mg group (p < 0.0001). There was a significant gender difference in the 0.4?mg group: LDL-C decreased by 44.4 ± 8.9% in women, compared with a decrease of 37.0 ± 0.9% in men (p < 0.046). In the PP group as a whole, total cholesterol decreased by 26.0 ± 0.5% from baseline in the 0.4mg group, compared with a decrease of 21.6 ± 0.7% in the 0.2mg group (p < 0.0001). Both doses were well tolerated; only eight (2.4 %) patients in the 0.4?mg group and five (3.1 %) patients in the 0.2?mg group withdrew owing to adverse events.

Cerivastatin 0.2?mg/day and 0.4?mg/day was found to lower low-density lipoprotein cholesterol and total cholesterol levels in a dose-dependent manner, with both doses exhibiting a good safety profile.     

Pharmacokinetic Effects of Simultaneous Administration of Single-Dose Gabapentin 500?mg and Zolpidem Tartrate 10?mg in Healthy Volunteers: A Randomized,Open-Label,Crossover Trial

Objective

Gabapentin is being investigated as a potential treatment for occasional disturbed sleep. This study assessed the pharmacokinetics and tolerability of gabapentin 500 mg and the commonly prescribed sedative/hypnotic zolpidem tartrate 10 mg, administered separately and in combination.

Methods

Forty healthy participants (19 male, 21 female) were randomized into this three-period crossover study [mean (range) age 34.1 (18–45) years, weight 68.3 (51.4–92.7) kg; 60 % white]. Participants were dosed with gabapentin alone (n = 39), zolpidem tartrate alone (n = 38), and the combination (gabapentin + zolpidem) (n = 38) over three treatment periods, which were separated by ≥7 days. Blood samples were collected pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 18, 24 and 36 h post-dose. Plasma concentrations of each drug were assayed using validated methods. Pharmacokinetic parameters were estimated from plasma concentration–time data using standard non-compartmental methods.

Results

For gabapentin + zolpidem combination versus gabapentin alone, mean pharmacokinetic parameters were peak plasma concentration (C_max) 4.61 versus 4.72 µg/mL, time to C_max (t_max) 4.63 versus 3.64 h and the area under plasma concentration–time curve extrapolated to infinity (AUC_0–∞) 53.4 versus 51.0 µg h/mL. For the combination versus zolpidem alone, mean pharmacokinetic parameters were C_max 154 versus 138 ng/mL, t_max 1.45 versus 1.84 h and AUC_0–∞ 912 versus 854 ng h/mL. The 90 % confidence intervals for C_max (rate of absorption) and AUC_0–∞ (extent of absorption) comparing the combination versus single drug administration fell within the 80–125 % range accepted for bioequivalence. All treatments were well tolerated.

Conclusion

The pharmacokinetics of gabapentin 500 mg and zolpidem tartrate 10 mg are unaffected when both drugs are taken simultaneously, compared with each drug taken alone.     

An open comparision of the diabetogenic effect of deflazacort and prednisone at a dosage ratio of 1.5 mg:1 mg

Objective: To compare the diabetogenic effects of deflazacort (D) versus prednisone (PN) using a dosage ratio of 1.5 mg deflazacort:1 mg prednisone. Methods: Thirty-three patients suffering from various active connective tissue or chronic inflammatory diseases were randomized to be treated with D or PN, assuming a therapeutic equipotency ratio of 1.5 mg D:1 mg PN. Neither dosage nor glucocorticoid employed were modified during the study. Patients had not received steroid treatment during the month prior to their inclusion date. Fasting glucose, glycosilated haemoglobin and fructosamine were determined before and after 1 month of treatment. Non-diabetic patients were also submitted to an oral glucose tolerance test (OGTT) at entry and after 1 month. Results were compared by univariate, and multivariate tests to correct the effects of age, body mass index and diagnosis. Results: After 1 month of treatment there were no differences between D and PN in fasting glucose, glycosilated haemoglobin, or fructosamine. OGTT performed after treatment showed similar glucose values for both treatment groups. Patients treated with D had insulin levels at min 60 of the post-treatment OGTT which were higher than those treated with PN [114.1 (62.8) mcUI · ml⁻¹ versus 73.5 (32.7) mcUI · ml⁻¹, P = 0.049], but the difference lost its statistical significance in the multivariate analysis. Conclusion: D and PN have similar effects on glucose tolerance when an equipotency ratio of 1.5 mg D:1 mg PN is employed. Previous studies employing a ratio of 1.2:1 mg may have understimated the adverse effects of D on glucose metabolism. Received: 9 July 1998 / Accepted in revised form: 30 October 1998     

Rofecoxib 12.5 mg,rofecoxib 25 mg,and celecoxib 200 mg in the treatment of symptomatic osteoarthritis: results of two similarly designed studies

ABSTRACT

Objective: To compare the efficacy of rofecoxib and celecoxib for the treatment of knee or hip OA over 6 weeks.

Methods: Two similarly designed, multicenter, randomized, double-blind, placebo-controlled studies. Patients were randomly assigned 3:3:3:1 in Study 1 to once daily (QD) rofecoxib 12.5?mg (N = 456), rofecoxib 25?mg (N = 459), celecoxib 200?mg (N = 456), or placebo (N = 150) and 3:3:1 in Study 2 to QD rofecoxib 25?mg (N = 471), celecoxib 200?mg (N = 460), or placebo (N = 151). There was no rofecoxib 12.5?mg arm in Study 2. The primary outcome measure of both studies was pain at night over 6 weeks for rofecoxib 25?mg vs. celecoxib 200?mg. Efficacy comparisons with rofecoxib 12.5?mg in Study 1 were included as pre-specified study objectives but not as pre-specified study hypotheses. Secondary endpoints included Patient Global Assessment of Response to Therapy (PGART) over 6 weeks and over 1 week. Safety was evaluated through the assessment of spontaneously reported adverse experiences (AEs), evaluation of vital signs, and laboratory data reported by investigators and patients.

Results: For the primary endpoint, reduction in pain at night over 6 weeks in Study 1 was not significantly different between active treatments; in Study 2 rofecoxib 25?mg significantly (?p = 0.023) reduced pain at night compared with celecoxib 200?mg over 6 weeks. For the secondary endpoints, in both studies, significantly (?p < 0.05) more patients treated with rofecoxib 25?mg than celecoxib 200?mg had a good or excellent PGART over 6 weeks, and over the first week (?p < 0.01). In both studies, there were no significant differences between active medications in the incidence of reported overall, serious, or drug-related AEs. The reported AE rates with the active treatments were generally similar to those with placebo in the two studies.

Conclusions: Rofecoxib 25?mg was significantly better than celecoxib 200?mg in relieving night pain at 6 weeks in one study; this was not confirmed in the accompanying study.     

A comparative double-blind study of loprazolam, 1 mg and 2 mg,versus placebo in anxiety-induced insomnia

Summary

A double-blind trial was carried out in 40 anxious in-patients with insomnia to compare the hypnotic effectiveness and tolerance of loprazolam, 1?mg and 2?mg, versus placebo. Groups of 10 patients received one or other dose of loprazolam or placebo for 7 nights and then placebo for the following 3 nights. Sleep quality and morning residual efiects were assessed each morning during the 10-day trial period by means of a sleep questionnaire. The results showed that I?mg loprazolam was superior to placebo but less effective than 2?mg loprazolam. No side-effects were reported at either dose level.     

Development of a Virosomal RSV Vaccine Containing 3D-PHAD® Adjuvant: Formulation,Composition, and Long-Term Stability

Purpose

Characterization of virosomes, in late stage preclinical development as vaccines for Respiratory Syncytial Virus (RSV), with a membrane-incorporated synthetic monophosphoryl lipid A, 3D-PHAD® adjuvant.

Methods

Virosomes were initially formed by contacting a lipid film containing 3D-PHAD® with viral membranes solubilized with the short chain phospholipid DCPC, followed by dialysis, later by adding solubilized 3D-PHAD to viral membranes, or to preformed virosomes from DMSO.

Results

Virosomes formed from lipid films contained the membrane glycoproteins G and F, at similar F to G ratios but lower concentrations than in virus, and the added lipids, but only a fraction of the 3D-PHAD®. By single particle tracking (SPT), the virosome size distribution resembled that seen by cryo-electron microscopy, but dynamic light scattering showed much larger particles. These differences were caused by small virosome aggregates. Measured by SPT, virosomes were stable for 300 days. 3DPHAD ® incorporation in virosomes could be enhanced by providing the adjuvant from DCPC solubilized stock, but also by adding DMSO dissolved adjuvant to pre-formed virosomes. Virosomes with 0.1 mg/mg of 3D-PHAD®/viral protein from DMSO induced antibody titers similar to those by virosomes containing 0.2 mg/mg of DCPC-solubilized 3D-PHAD®.

Conclusions

Stable 3D-PHAD® adjuvanted RSV virosomes can be formulated.

     

Efficacy of etoricoxib 60 mg/day and diclofenac 150 mg/day in reduction of pain and disability in patients with chronic low back pain: results of a 4‐week,multinational, randomized,double-blind study

ABSTRACT

Background and methods: The efficacy and safety of etoricoxib 60?mg/day in patients with established chronic low back pain (CLBP) were compared with those of diclofenac 150?mg/day in a 4‐week, multicentre, randomized, double-blind, parallel-group trial. Four hundred and forty-six adult patients with CLBP (Quebec Task Force on Spinal Disorders Class 1 or 2) and with worsening pain upon discontinuation of pre-study analgesic medication were enrolled in the study.

The study primary efficacy endpoint was change from baseline in Low Back Pain Intensity Scale (LBP‐IS) score over the 4‐week treatment period. Secondary and other efficacy endpoints included: changes in Roland and Morris Disability Questionnaire (RMDQ), Patient Global Assessment of Response to Therapy (PGART) and Low Back Pain Bothersomeness Scale (LBP-BS) scores. Early efficacy was assessed using PGART and LBP‐IS scores 4?h after the first dose on the mornings of Days 1, 2 and 3. The overall safety and tolerability of etoricoxib 60?mg/day during 4 weeks of treatment were also assessed.

Results: The least-squares mean time-weighted change from baseline LBP‐IS score over 4 weeks was –32.94?mm (95% CI –36.25, –29.63) for etoricoxib, indicating substantial efficacy in relief of pain. The treatment difference for the primary outcome was 2.51?mm (95% CI –1.50, 6.51), fulfilling the prespecified equivalence criterion of 95% confidence interval wholly within ± 10?mm. Etoricoxib improved all secondary and other efficacy outcomes.

There were no statistically significant between-group differences in the proportion of patients with one or more clinical adverse events (AEs) (etoricoxib 35%, diclofenac 39%), or the proportion of patients who discontinued due to AEs (etoricoxib 7%, diclofenac 5%).

Conclusions: The results of this study confirm that, for adult patients with CLBP, etoricoxib 60?mg once daily over 4 weeks is effective for relief of pain and improvement of physical function and comparable to high-dose diclofenac 150?mg daily.     

A pharmacokinetic study investigating the rate of absorption of a 500 mg dose of a rapidly absorbed paracetamol tablet and a standard paracetamol tablet

ABSTRACT

Objective: A rapidly absorbed tablet formulation of paracetamol containing sodium bicarbonate (PS) has been previously shown to be absorbed at least twice as fast as a standard paracetamol tablet (P) at a 1?g dose. In South America and Asia it is customary for patients to take a 500?mg dose of analgesic. The objective of this pharmacokinetic study was to compare the rate of absorption of PS versus P at a 500?mg dose.

Research design and methods: An open, randomized, single dose, cross-over study. Thirty Hispanic healthy volunteers randomly received a 500?mg dose taken orally with 50?mL of water 2?h after a standard breakfast. Blood samples were taken up to 10?h post-dose. Plasma concentrations of paracetamol were determined by HPLC with UV detection.

Main outcome measures: AUC_{0–30 min}, C_{plasma 30 min} and T_max were analyzed non-parametrically by the Wilcoxon's rank sum test. A linear mixed effects model was used to analyze the logarithmically transformed AUC_0–∝ and C_max. Bioequivalence was accepted if the 90% confidence intervals (CI) for the ratio of the means of the primary pharmacokinetic variable AUC_0–∝ lay completely within the range 0.80–1.25.

Results: AUC_{0–30 min} and C_{plasma 30 min} were significantly greater and T_max was significantly shorter (all p < 0.0001) for PS versus P. The formulations were bioequivalent for AUC_0–∝ (90% CI 0.99:1.05) and no statistical difference was seen for C_max (95% CI 0.91:1.14).

Conclusions: Paracetamol was absorbed at least twice as fast from PS compared to P at a 500?mg dose. The extent of absorption was equivalent for both formulations.     

Double-blind comparison of meptazinol (200 mg) and dextropropoxyphene/paracetamol in a multi-centre,general practice setting

Summary

A multi-centre, double-blind, double-dummy trial was carried out in general practice to compare the effectiveness and tolerance of oral meptazinol with dextropropoxyphene/paracetamol in patients with acute or chronic painful conditions. Patients received doses of 400?mg meptazinol or 65?mg dextropropoxyphene plus 650?mg paracetamol every 3 to 6 hours as required up to a maximum of 4 doses per day over a period of 14 days. No significant difference in analgesic efficacy, as assessed by the patients on a visual analogue pain rating scale, was found between the two treatments. The results are discussed in terms of the benefit/risk ratio of polypharmic and single compound drugs.     

Efficacy of flurbiprofen 8.75 mg lozenge in patients with a swollen and inflamed sore throat

Objective: Sore throat is often over-treated with antibiotics, therefore there is a need for non-antibiotic treatments that provide effective relief. From the patient’s point of view, symptoms of pharyngeal inflammation such as a “swollen” and “inflamed” throat are often considered the most bothersome; so, a non-steroidal anti-inflammatory drug could be an appropriate treatment. We investigated the efficacy and safety of flurbiprofen 8.75?mg lozenge in adults with a swollen and inflamed throat.

Research design and methods: We enrolled adults with moderate-to-severe sore throat and evidence of tonsillo-pharyngitis into a randomized, double-blind study. Patients received flurbiprofen 8.75?mg or placebo lozenges every 3–6?hours as needed (up to five lozenges in 24?hours) and rated their symptoms (sore throat pain, difficulty swallowing and the sensation of a swollen throat) on standard linear scales regularly over 24?hours. The efficacy of flurbiprofen lozenge was determined in patients reporting a swollen and inflamed throat at baseline, as well as those with relatively severe symptoms.

Clinical trial registration: ClinicalTrials.gov NCT01049334.

Main outcome measures: The main outcome measures were the time-weighted summed differences in patient-reported sore throat pain, difficulty swallowing and swollen throat over 24?hours.

Results: Out of 204 patients, 124 (60.8%) described their throats as swollen and inflamed at baseline. Flurbiprofen lozenges provided greater relief than placebo over 24?hours: 79.8%, 99.6% and 69.3% (for sore throat pain, difficulty swallowing and swollen throat, respectively, all P?≤?0.01). These outcomes were more substantial in patients with relatively severe symptoms. No serious or unexpected adverse events occurred.

Conclusions: Flurbiprofen 8.75?mg lozenge appears to provide effective, well-tolerated relief of sore throat, difficulty swallowing and swollen throat in adults with a swollen and inflamed throat, as well as those with relatively severe symptoms. A limitation of these findings is that, while predetermined, these are secondary outcomes derived from a targeted sub-group of patients, not the entire study population.     

Vasodilation Effects of RGD Containing Peptides and De rivatives

已经证实纤维蛋白分子内两个区域内的氨基酸序列可以介导纤维蛋白与ＧＰＩｂ／Ｉ┐Ｉａ受体的结合。除单克隆抗体外，用合成的含ＲＧＤ和ＡＰＬＲＶ的小分子多肽可以封闭ＧＰＩｂ／Ｉ┐Ｉａ的这种结合功能，我们的初步研究发现，ＲＧＤＳ除具有抑制血小板聚集和抗血栓形成的作用外，还显示舒血管作用。为了证实ＲＧＤＳ相关多肽的舒血管作用，研究了ＲＧＤＦ，ＡＰＬＲＶ，ＡＰＬＲＶＲＧＤＳ，ＡＰＬＲＶＲＧＤＦ，在体外用ＮＥ预处理大鼠的动脉肌条后观察了上述合成多肽的舒血管作用，检测了三种剂量（１０┐５ｍｏｌ／Ｌ，１０┐６ｍｏｌ／Ｌ，１０┐７ｍｏｌ／Ｌ）下收缩的肌条舒张的程度。     

Antiplatelet Aggregation Effects of YIGSK and RGD Containing Peptides

观察了ＹＩＧＳＫ，ＲＧＤＳ，ＲＧＤＶ，ＲＧＤＦ，ＹＩＧＳＫＲＧＤＳ，ＹＩＧＳＫＲＧＤＶ和ＹＩＧＳＫＲＧＤＦ的抗血小板聚集作用，通过比较它们的活性，发现将ＹＩＧＳＫ和含ＲＧＤ多肽偶联可增强某些化合物的抗血小板聚集活性     

Efficacy and tolerability of the single-pill combination of aliskiren 300 mg/amlodipine 10 mg in hypertensive patients not controlled by olmesartan 40 mg/amlodipine 10 mg

Abstract

Objective:

We aimed to investigate whether the single pill combination (SPC) of aliskiren 300?mg and amlodipine 10?mg (ALIS 300/AMLO 10) improves blood pressure (BP) reduction in hypertensive patients not adequately controlled by the SPC olmesartan 40?mg and amlodipine 10?mg (OLM 40/AMLO 10).     

Inflammation and cancer: a failure of resolution?

There are clear links between chronic inflammation and cancer; strong epidemiological and genetic evidence indicates that inflammation can drive tumour progression, and more-recent evidence indicates that the disruption of endogenous anti-inflammatory mechanisms in mice can lead to tumour development. The resolution of inflammation is an active coordinated process that requires the production of anti-inflammatory mediators, the termination of proinflammatory signalling pathways and the appropriate clearance or migration of inflammatory cells. Disruption of any of these processes can lead to chronic persistent inflammation and tumour growth. Although the mediators and mechanisms that drive inflammation have become increasingly well characterized, the endogenous mechanisms that limit the inflammatory response, and particularly their role in cancer, are unclear. There are clear opportunities for drug discovery and the development of new therapeutic approaches that target tumour-associated inflammation and the mechanisms of chronic inflammation.     

Is obesity a disease of the blood-brain barrier? Physiological,pathological, and evolutionary considerations

Leptin has emerged as a major regulator of body adiposity. The majority of humans with obesity have a resistance to leptin. Human and rodent studies indicate that the major cause of this resistance arises from an impaired ability of leptin to cross the blood-brain barrier, with lesser roles played by receptor and post-receptor defects. Evidence from baboons living in the wild is consistent with the hypothesis that during most of evolution serum levels of leptin were much lower than those currently considered normal. Leptin may have evolved to signal to the brain when caloric reserves were adequate to engage in reproductive and other behaviors not immediately concerned with acquisition of calories. The leptin transporter is a regulated system, with the rate of transport being increased by alpha(1) adrenergic agents and decreased by starvation. Impaired regulation of the transporter or impairments in transporter production could underlie the resistance caused by transporter defects. Evolutionary pressures would not have selected against such impairments if leptin levels were lower than those typically seen in Western society. A model that could explain how leptin transporter resistance can be acquired is presented.     

Efficacy and safety of linagliptin 2.5 mg twice daily versus 5 mg once daily in patients with type 2 diabetes inadequately controlled on metformin: a randomised, double-blind, placebo-controlled trial

Abstract Objective: Glycaemic control in patients with type 2 diabetes (T2DM) is often not achieved or not sustained using monotherapy such as metformin, necessitating the addition of other antihyperglycaemic agents. Linagliptin, a dipeptidyl peptidase-4 inhibitor, is licensed for 5?mg once-daily dosing. As metformin is administered twice daily, a fixed-dose combination of these compounds would require twice-daily administration of linagliptin. This study evaluated whether 2.5?mg twice-daily dosing of linagliptin has comparable efficacy and safety to 5?mg once-daily dosing when given in addition to metformin twice daily in patients with inadequate glycaemic control. Methods: A total of 491 T2DM patients with glycated haemoglobin (HbA1c) 7.0-10.0% were randomised (5:5:1) to double-blind treatment with linagliptin 2.5?mg twice daily, 5?mg once daily or placebo, respectively, in addition to continuing metformin twice daily (≥1500?mg/day or maximally tolerated dose). The primary endpoint was change from baseline in HbA1c after 12 weeks. ClinicalTrials.gov, NCT01012037. Results: Mean baseline HbA1c for all patients was 7.97%. After 12 weeks, linagliptin 2.5?mg twice daily and 5?mg once daily both significantly reduced HbA1c (placebo-adjusted changes from baseline -0.74% (95% CI -0.97, -0.52) and -0.80% (95% CI -1.02, -0.58), respectively, both p?相似文献   

A pharmacokinetic study comparing single and repeated oral doses of 20 mg and 40 mg omeprazole and its two optical isomers, S-omeprazole (esomeprazole) and R-omeprazole, in healthy subjects

Objective To investigate the pharmacokinetics of S-omeprazole (esomeprazole), R-omeprazole and racemic omeprazole following single and repeated oral doses of 20 mg and 40 mg of each compound in healthy male and female subjects.Methods In an open, randomised, three-way, cross-over study, 12 subjects received 20 mg and another 12 subjects received 40 mg S-omeprazole, R-omeprazole and racemic omeprazole as oral solutions once daily for 5 days, separated by washout periods of at least 10 days. Blood samples were taken for analysis pre-dose and at selected time points during a 12-h period following drug administration on study day 1 and day 5. Pharmacokinetic parameters of S-omeprazole, R-omeprazole, racemic omeprazole and the two main metabolites (5-hydroxy and sulphone) were calculated using non-compartmental analysis.Results Following the 20-mg dose of each compound, values of the total area under the plasma concentration–time curve (AUC) were 1.52, 0.62 and 1.04 mol h/l for S-omeprazole, R-omeprazole and racemic omeprazole, respectively, on day 1. Respectively, AUC values on day 5 were 2.84, 0.68 and 1.63 mol h/l. Corresponding values after the 40-mg doses were 3.88, 1.39 and 2.44 mol h/l on day 1 and 9.32, 1.80 and 5.79 mol h/l on day 5.Conclusion Treatment with S-omeprazole (esomeprazole; 20 mg and 40 mg) resulted in higher AUC values than with either R-omeprazole or racemic omeprazole after both single and repeated doses due to a lower metabolic rate of S-omeprazole than R-omeprazole and, consequently, racemic omeprazole. S-Omeprazole, R-omeprazole and the racemate were well tolerated.     

Comparison of the adverse event profiles of levofloxacin 500 mg and 750 mg in clinical trials for the treatment of respiratory infections

ABSTRACT

Objective: To compare safety data with levofloxacin 500?mg and 750?mg from clinical trials for the treatment of respiratory infections.

Methods: We compared adverse event data for levofloxacin 500?mg and 750?mg from clinical trials in acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis, and community-acquired pneumonia. Adverse events occurring after the initiation of therapy were classified as treatment-emergent adverse events (TEAE); drug-related adverse events (DRAE) were TEAE assessed by the clinical investigator as definitely/very likely or probably related to levofloxacin therapy.

Results: Overall, the safety profile of the two doses was similar but not identical. TEAE occurred in 49.0% (1601/3268) of those treated with 500?mg and in 45.5% (519/1141) of those treated with 750?mg (?p = 0.042); the corresponding rates of DRAE were 7.6% (248/3268) and 8.0% (91/1141) (?p = 0.699). There was no statistically significant difference in terms of overall TEAE and DRAE rates within each of the three infectious conditions, but there were in specific events, all of which are expected with levofloxacin therapy. The limitations of this analysis include that it utilized a subset of available safety data, that it includes data only from clinical trials, and that we report primarily on events occurring in ≥ 2% of patients.

Conclusions: Given similar adverse event profiles and the advantages of higher dose therapy, including shorter courses of therapy and potential impact on preventing resistance, clinicians should consider utilizing the 750?mg dose of levofloxacin when choosing between dosage strengths for treatment of indicated infections.