Evaluation of the long-term safety and effectiveness of tadalafil once daily in Chinese men with erectile dysfunction: Interim results of a multicenter, randomized, open-label trial / 亚洲男科学杂志(英文版)

Once-daily tadalafil administration has been well established; however, studies about tadalafil once-daily treatment in the Chinese population are lacking. In this phase 4, postmarketing study, we ascertained the long-term safety and effectiveness of tadalafil 2.5 mg and 5.0 mg once daily in Chinese men with erectile dysfunction (n = 635). The primary endpoint of the study was safety at 12 months as assessed by the proportion of patients experiencing at least one treatment-emergent adverse event (serious or nonserious). The secondary endpoints included safety and effectiveness, measured by the International Index of Erectile Function-Erectile Function (IIEF-EF) domain scores. Similar adverse events to the known safety profile of tadalafil, such as nasopharyngitis, upper respiratory tract infection, headache, and dizziness, were detected. No new cardiovascular safety concerns were observed. After 3 months of treatment, significant increases in IIEF-EF domain scores were detected for both 2.5-mg (least squares [LS] mean change: 6.3; 95% confidence interval [CI]: 5.4-7.1; P < 0.001) and 5.0-mg (LS mean change: 7.4; 95% CI: 6.8-7.9; P < 0.001) tadalafil doses, and significance was maintained up to 12 months. In addition, approximately 40% of patients regained normal erectile function (IIEF-EF ≥26) following 1 year of tadalafil once-daily treatment. The findings in this study provide evidence for the extended effectiveness and tolerability of tadalafil, demonstrating no new safety concerns, in a Chinese population and make once-daily tadalafil administration a viable option for improving sexual performance and satisfaction in Chinese men with erectile dysfunction.

Evaluation of the long-term safety and effectiveness of tadalafil once daily in Chinese men with erectile dysfunction: interim results of a multicenter, randomized, open-label trial / 亚洲男科学杂志(英文版)

Once-daily tadalafil administration has been well established; however, studies about tadalafil once-daily treatment in the Chinese population are lacking. In this phase 4, postmarketing study, we ascertained the long-term safety and effectiveness of tadalafil 2.5 mg and 5.0 mg once daily in Chinese men with erectile dysfunction (n = 635). The primary endpoint of the study was safety at 12 months as assessed by the proportion of patients experiencing at least one treatment-emergent adverse event (serious or nonserious). The secondary endpoints included safety and effectiveness, measured by the International Index of Erectile Function-Erectile Function (IIEF-EF) domain scores. Similar adverse events to the known safety profile of tadalafil, such as nasopharyngitis, upper respiratory tract infection, headache, and dizziness, were detected. No new cardiovascular safety concerns were observed. After 3 months of treatment, significant increases in IIEF-EF domain scores were detected for both 2.5-mg (least squares [LS] mean change: 6.3; 95% confidence interval [CI]: 5.4-7.1; P < 0.001) and 5.0-mg (LS mean change: 7.4; 95% CI: 6.8-7.9; P < 0.001) tadalafil doses, and significance was maintained up to 12 months. In addition, approximately 40% of patients regained normal erectile function (IIEF-EF ≥26) following 1 year of tadalafil once-daily treatment. The findings in this study provide evidence for the extended effectiveness and tolerability of tadalafil, demonstrating no new safety concerns, in a Chinese population and make once-daily tadalafil administration a viable option for improving sexual performance and satisfaction in Chinese men with erectile dysfunction.

Study of Efficacy and Safety in the Administration of 400 mg of Amikacin Sulfate Administered Once Daily to Elderly Patients / 医薬品情報学

<b>Objective: </b>In previously reported comparisons of aminoglycoside antimicrobials administered once daily versus multiple administration, toxicity was found to be equal or lower while efficiency remained high.  However, there are few reports on the clinical condition of targeted elderly persons.  The objective of this study was to evaluate the once-daily dosing regimen of 400 mg of AMK involving elderly pneumonia patients aged 75 years or older with regard to clinical evaluation including the efficacy and toxicity.<br><b>Methods: </b>A survey to clinically evaluate the efficacy and toxicity of 400 mg AMK administered once daily for 30 min at 24 h intervals was carried out.  One hundred twenty-seven patients with pneumonia and who were 75 years or older at Funabashi General Hospital were targeted, with the aim of an expected clinical effect of <i>C</i>_max/MIC≥ 8-10.  Serum concentration monitoring was carried out after administration began.<br><b>Results: </b>There were 121 patients (95.3%) of controlled AMK concentration with a trough serum concentration of <10 μg/mL, which is a safe concentration range.  There were 6 patients (4.7%) where trough serum concentration in the toxic range >10 μg/mL, with an average at 15.1±5.0 μg/mL, and the average administration days were 7.5 ± 3.3 days.  Moreover, before/after AMK administration, there were 3 patients (2.4%) where CRE values increased more than a 150% over the previous values, and were evaluated as renal dysfunction.  Average trough serum concentration at that time was 3.6 ± 1.1 μg/mL, and average number of days of administration were 13 ± 1.4 days.  Patients of trough serum concentration in the toxic range >10 μg/mL were not included.  The average peak serum concentration calculated by Winter’s pharmacokinetic parameter and the 1-compartment model was 35.3 ± 8.0 μg/mL, and the average <i>C</i>_max/MIC which correlates with the AMK effect was 9.9 ± 2.2.  The treatment was effective for 83 (65.4%) of the 127 patients.<br><b>Conclusion: </b>By once-daily administration of AMK 400 mg to aged persons 75 years or older, change in trough serum concentration into a safe range and <i>C</i>_max/MIC≥ 8-10, the level at which clinical effectivity can be expected, could be achieved.  This administration method is shown to be useful in maintaining AMK in the target serum concentration range for aged persons.

Once daily dosing of aminoglycoside in children / 소아과

Aminoglycosides are frequently used antibiotics in children. The multiple daily dosing (MDD) in infants and children is twice or three times daily depending on age. Recent studies in adults have shown that once daily dosing (ODD) maximizes the bactericidal activity and might minimize the toxicity of antibiotics. So, I reviewed many studies about efficacy, toxicity and cost effectiveness of ODD of aminoglycosides in children. Most studies suggest that ODD compared with MDD of aminoglycosides is theoretically more efficacious and has no higher toxicity in infants and children. But, the total number of patients included in the studies is not large. Multi-center, controlled prospective studies are required in larger numbers of infants and children to determine the efficacy and safety of the ODD regimen in children before ODD of aminoglycosides can be recommended for routine use.