No abstract

IBKM can estimate not only the urea kinetics of an actual hemodialysis, but it can also predict a patient's target hemodialysis dose for any desired, flexible hemodialysis treatment. The method should prove useful for bedside monitoring, forecasting, and fine tuning of hemodialysis dose.

AimsThe pharmacokinetic profile of candesartan cilexetil might be altered in patients with end-stage renal disease (ESRD). No data are available about the pharmacokinetics and haemodynamics of the angiotensin II receptor antagonist candesartan cilexetil in ESRD patients on regular haemodialysis (HD). Methods We performed a repeated dose study (8 mg candesartan cilexetil once daily) in eight male HD patients over a treatment period of 5 days with an additional observation period of 3 days. Results Pharmacokinetic analysis with nonlinear mixed effects modeling (NONMEM) over the whole treatment period revealed a dependency of the volume of distribution on body weight and of the metabolic clearance on age and body weight in the studied population. No significant drug elimination by HD was observed. The estimated metabolic and intercompartmental clearances were 83 ml min −1 (CV 39%) and 9.9 ml min −1 , respectively. The unexplained random variability of the final two compartment model was 30%. In one patient with adult polycystic kidney disease oral clearance decreased during the observation period, attributable to a significant increase in bioavailability. Maximum observed changes in blood pressure were −50/−27±14/8 mmHg on day 5 with haemodialysis therapy as compared with changes in blood pressure of −14/−12±14/8 mmHg on day 1 without haemodialysis treatment. The observed maximum decrease in systolic blood pressure correlated with the amount of ultrafiltration during the HD session on day 5 (r=0.70, P<0.05). In two patients, one of whom was binephrectomized, severe hypotensive episodes were observed during this HD session. Conclusions HD does not influence the elimination kinetics of candesartan. The observed inter-and intraindividual variability of oral clearance and the pronounced influence of HD-induced volume contraction on the haemodynamic effects of candesartan makes it mandatory to carefully monitor HD patients treated with candesartan cilexetil.Keywords: candesartan cilexetil, hypertension, haemodialysis, NONMEM. This Angiotensin II receptor antagonists have recently been introduced as a new therapeutic class for the treatment prodrug is rapidly and completely converted to the active compound candesartan during gastrointestinal absorption of arterial hypertension. Candesartan, one of the currently available angiotensin II receptor antagonists, is a benzimid- [3][4][5]. In healthy subjects 67% of an oral dose of candesartan is excreted in faeces [6] and only about 5% azole carboxylic acid derivative with a long-lasting antagonism of the angiotensin II type I receptor.to 10% of the administered dose is excreted unchanged in the urine in 24 h [7,8]. Studies with candesartan Since candesartan itself is poorly absorbed after oral administration the ester prodrug candesartan cilexetil cilexetil in healthy volunteers and patients with hypertension have shown a significant and long lasting decrease ofCorrespondence: Dominik E. Uehlinger, M.D., Division of Nephrology, systolic and diastolic blood pressure [7,[9][10]...

The described population pharmacokinetic model allows individualization of vancomycin dosing intervals in patients receiving hemodialysis, based on patient characteristics and urea kinetic modeling.

The large interindividual variability of utility values precludes a prediction about the acceptance of a new therapeutic regimen by an individual patient. The assessment of the utility enables, however, a more objective judgment of the general acceptance of any possible risk/benefit ratio induced by a new immunosuppressive regimen in our patient population.