Pharmacokinetics and pharmacodynamics of candesartan cilexetil in patients with normal to severely impaired renal function

Objective: We studied the pharmacokinetics and pharmacodynamics of single and multiple doses of candesartan cilexetil 8 mg per day in hypertensive patients with different degrees of renal function impairment. Candesartan is an angiotensin II subtype I (AT1) receptor antagonist that is administered orally as candesartan cilexetil which is converted in the active compound. Methods: Twenty-three patients were included, divided into groups according to creatinine clearance (cr cl. group A > 60 nl.min(-1).73 m(-2), group B 30-60 ml.min(-l).1.73 m(-2) and group C 15-30 ml. min(-1).1.73 m(-2)). Results: Trough serum concentrations of candesartan were higher in group C compared with group A. The values did not increase after multiple dosing, indicating absence of accumulation. There was a significant negative correlation between the area under the concentration-time curve extrapolated to time infinity (AUC(inf)) and the glomerular filtration rate (GFR) indicating a lower renal clearance of candesartan in patients with impaired renal function. The onset of haemodynamic and hormonal effects was gradual. During the single-dose study blood pressure as well as plasma renin activity (PRA) and angiotensin II were unchanged at peak. At day 5 of the multiple-dose study blood pressure was lower and both PRA and angiotensin II were higher compared with baseline. Conclusion: Although serum trough levels increased during repeated administration and half-lift: was higher in patients with impaired renal function, candesartan cilexetil at a dose of 8 mg per day does not lead to drug accumulation in these patients. This dose is effective in lowering blood pressure and appears to be suitable for patients with renal function impairment

Neutrophil function capacity to express CD10 is decreased in patients with septic shock

Objective: To evaluate the performance of a newly developed assay to assess neutrophil function capacity, After optimization, the assay was performed on samples derived from patients with septic shock and compared with healthy controls and patients with a systemic viral infection, Design: Prospective evaluation of the performance of a new assay. Settings: Medical intensive care unit, hospital laboratory, Patients: Ten patients with septic shock, ten patients with infectious mononucleosis, and ten healthy controls. Measurements and Main Results: We report an assay to assess neutrophil function capacity, in which CD10 membrane expression is measured by FAGS before and after in vitro stimulation with Staphylococcus aureus bacteria, This assay evaluates the early activation state of circulating neutrophils and is shown to be of value in diagnosing a sepsis syndrome, First the assay was optimized, As an anticoagulant, sodium-citrate gave the best results, Blood samples must be kept on ice to reduce activation inside the siliconized tube and can be stored in this way for at least 8 hrs without affecting the test results, Kinetic studies showed a maximal expression of CD10 on neutrophils of healthy volunteers after 15 mins of stimulation with S. aureus bacteria, Second, the test was performed on samples derived from ten septic patients and ten patients with infectious mononucleosis, Septic patients had a significantly decreased CD10 expression capacity compared with healthy controls. Patients with infectious mononucleosis have a significantly higher CD10 expression capacity compared with septic patients, but in approximately one half of them, the expression capacity was below the range found in controls, Conclusions: These results indicate that in circulating neutrophils, the secretory vesicles have been mobilized completely in patients with septic shock. The assay proves to be of acceptable analytical quality and can be quickly and easily performed. Regarding clinical performance, this assay may be helpful in diagnosing septic shock

Pharmacokinetics and pharmacodynamics of candesartan cilexetil in patients with normal to severely impaired renal function

Objective: We studied the pharmacokinetics and pharmacodynamics of single and multiple doses of candesartan cilexetil 8 mg per day in hypertensive patients with different degrees of renal function impairment. Candesartan is an angiotensin II subtype I (AT1) receptor antagonist that is administered orally as candesartan cilexetil which is converted in the active compound. Methods: Twenty-three patients were included, divided into groups according to creatinine clearance (cr cl. group A > 60 nl.min(-1).73 m(-2), group B 30-60 ml.min(-l).1.73 m(-2) and group C 15-30 ml. min(-1).1.73 m(-2)). Results: Trough serum concentrations of candesartan were higher in group C compared with group A. The values did not increase after multiple dosing, indicating absence of accumulation. There was a significant negative correlation between the area under the concentration-time curve extrapolated to time infinity (AUC(inf)) and the glomerular filtration rate (GFR) indicating a lower renal clearance of candesartan in patients with impaired renal function. The onset of haemodynamic and hormonal effects was gradual. During the single-dose study blood pressure as well as plasma renin activity (PRA) and angiotensin II were unchanged at peak. At day 5 of the multiple-dose study blood pressure was lower and both PRA and angiotensin II were higher compared with baseline. Conclusion: Although serum trough levels increased during repeated administration and half-lift: was higher in patients with impaired renal function, candesartan cilexetil at a dose of 8 mg per day does not lead to drug accumulation in these patients. This dose is effective in lowering blood pressure and appears to be suitable for patients with renal function impairment