New once daily mesalamine formulations may improve adherence to medication usage.Response to Asacol and other forms of 5-aminosalicyclic acid(5-ASA)is better correlated with tissue concentrations and best predicted by...New once daily mesalamine formulations may improve adherence to medication usage.Response to Asacol and other forms of 5-aminosalicyclic acid(5-ASA)is better correlated with tissue concentrations and best predicted by concentrations of the drug within the lumen of the colon.Our group used computer simulation to predict colonic 5-ASA levels after Asacol administration.In our study,the model simulated Asacol distribution in the healthy colon,and during quiescent and active ulcerative colitis.An Asacol dosage of 800 mg,threetimes a day,was compared to 2400 mg given once a day.Under ideal conditions,the predicted maximum drug in the total colon and individual colonic segments over 100 d differed by less than 3%between single and multiple doses.Despite changes in motility and defection rates,the predicted maximum and average 5-ASA concentrations in the total colon and individual colonic segments differed by less than 10%between dosing regimens.Asymmetric distribution of 5-ASA in the colon was influenced by frequency of bowel movements and colonic transit rate.In active colitis,sigmoid 5-ASA concentration becomes negligible.Our model supports once daily administration of Asacol as standard treatment for ulcerative colitis.展开更多
Casals et al have reported an inverse correlation between serum phosphate and body weight after administration of sodium phosphate at a dose of 60 g. Our group has already described the relationship between body weigh...Casals et al have reported an inverse correlation between serum phosphate and body weight after administration of sodium phosphate at a dose of 60 g. Our group has already described the relationship between body weight and hyperphosphatemia with these preparations, although our study was not quoted by Casals. We performed a pharmacokinetic study involving 13 volunteers who were divided into two groups on the basis of body weight： group I consisting of seven women with a median weight of 60 kg and group Ⅱ consisting of five men and one woman with a median weight of 119.2 kg. Group Ⅰdeveloped higher peak phosphate levels and maintained these levels above the subjects in Group Ⅱ for a prolonged time period despite adequate hydration being ensured with frequent monitoring of weight, fluid intake and total body weight. Our studydemonstrated that adequate hydration does not protect against the secondary effects of hyperphosphatemia. In the study by Casais et al, 66% of the study subjects were women, the correlation between serum phosphate and gender in their data also appears to be important. Women are at higher risk of acute phosphate nephropathy due to a diminished volume of distribution of the high dose of ingested phosphate. Decreased volume of distribution in women is due to diminished body weight. This is further compounded by decreased creatinine clearance in females.展开更多
文摘New once daily mesalamine formulations may improve adherence to medication usage.Response to Asacol and other forms of 5-aminosalicyclic acid(5-ASA)is better correlated with tissue concentrations and best predicted by concentrations of the drug within the lumen of the colon.Our group used computer simulation to predict colonic 5-ASA levels after Asacol administration.In our study,the model simulated Asacol distribution in the healthy colon,and during quiescent and active ulcerative colitis.An Asacol dosage of 800 mg,threetimes a day,was compared to 2400 mg given once a day.Under ideal conditions,the predicted maximum drug in the total colon and individual colonic segments over 100 d differed by less than 3%between single and multiple doses.Despite changes in motility and defection rates,the predicted maximum and average 5-ASA concentrations in the total colon and individual colonic segments differed by less than 10%between dosing regimens.Asymmetric distribution of 5-ASA in the colon was influenced by frequency of bowel movements and colonic transit rate.In active colitis,sigmoid 5-ASA concentration becomes negligible.Our model supports once daily administration of Asacol as standard treatment for ulcerative colitis.
文摘Casals et al have reported an inverse correlation between serum phosphate and body weight after administration of sodium phosphate at a dose of 60 g. Our group has already described the relationship between body weight and hyperphosphatemia with these preparations, although our study was not quoted by Casals. We performed a pharmacokinetic study involving 13 volunteers who were divided into two groups on the basis of body weight： group I consisting of seven women with a median weight of 60 kg and group Ⅱ consisting of five men and one woman with a median weight of 119.2 kg. Group Ⅰdeveloped higher peak phosphate levels and maintained these levels above the subjects in Group Ⅱ for a prolonged time period despite adequate hydration being ensured with frequent monitoring of weight, fluid intake and total body weight. Our studydemonstrated that adequate hydration does not protect against the secondary effects of hyperphosphatemia. In the study by Casais et al, 66% of the study subjects were women, the correlation between serum phosphate and gender in their data also appears to be important. Women are at higher risk of acute phosphate nephropathy due to a diminished volume of distribution of the high dose of ingested phosphate. Decreased volume of distribution in women is due to diminished body weight. This is further compounded by decreased creatinine clearance in females.
