Serious adverse events dose range

Phase 1 dose-escalating and PK studies of Vatalanib were performed on a wide spectrum of tumors including colorectal, RCC, NSCLC, AML, ghoblas-toma, and prostate cancer. Dose ranged up to 2000 mg once daily or 1000 mg twice daily by oral administration. In most studies, results in patients with advanced solid tumors indicated that treatment was well tolerated with no drug-related serious adverse events. Tumor volume reduction was observed in some patients. The MTD was not reached with doses up to 1500 mg/day. The optimal dose was determined as 1250 mg/day. Measurable responses of tumor volume reduction were observed in 19% and 4% of the patients with RCC and ghoblastoma, respectively. Over 50% of patients achieved stable disease [282]. 

In 2007, Boocock et al. [2007] were the first to publish a complete phase I dose pharmacokinetic study in humans. Ten healthy volunteers were recruited to consume single doses of oral resveratrol (0.5, 1, 2.5, or 5 g). Consumption of resveratrol did not cause serious adverse events. Analyses of resveratrol and its metabolites were performed by LC-MS/MS. In plasma in all intake doses resveratrol-3-sulfate (56%) was the highest metabolite, the second and third metabolites were monoglucuronides (17 and 23%, respectively), and, finally, the lowest was free resveratrol (5%). Resveratrol was rapidly absorbed, the 7/nax for all metabolites ranged between 0.8 and 2.4 h, although the half-lives of free resveratrol and the conjugated forms remained for a long time in plasma, between 2.9 and 11.5 h. 

For the children <30 months of age, development ranained within the average range, as determined by the Bayley Scales of Infant and Toddler Development. Mean z-scores for height, weight, and head circumference, as determined by the Center for Disease Control reference values, were maintained with no statistically significant change from baseline. Sapropterin had a favorable safety profile and was well tolerated, based on dose adherence and absence of serious adverse events. The reported AEs and drug-related AEs were consistent with adverse reactions reported in the earlier studies of sapropterin in PKU subjects 4-8 years of age [12]. 

Susceptibility factors Children Studies on the use of erythropoietin derivatives in children have suggested that although children need almost the same doses of erythropoietin derivatives as are used in adults range and should be dosed according to the hemoglobin deficit and not according to body weight, there is no evidence of unexpected serious adverse events attributable to erythropoietin derivatives [87, 88", 89"]. 

In 224 women aged 20-89 years, desmopressin 0.1—0.4 mg/day was used for treating nocturia (43). There were five adverse events, four of which were reported in the dose-titration period. Of these four events, two were deaths that were not thought to be due to hyponatremia and two were due to serious hyponatremia. The fifth case occurred during the double-blind period in the placebo group. In 27 patients serum sodium concentrations were below the reference range and in 13 they were less than 130 mmol/1 11 of the 13 were aged 65 years or older. 

---