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Purpose: The efficacy of the vitamin D analog paricalcitol has mainly been shown in short-term studies. There are limited data regarding long-term treatment with this agent. This purpose of this study was to determine long-term effects of paricalcitol therapy on parathyroid hormone (PTH) suppression and serum levels of calcium, phosphorus and calcium-phosphorus product (Ca x P)., Patients and Methods: Patients who received paricalcitol for > or = 3 months had the following data collected: demographics, drug dosage, serum PTH, corrected serum calcium concentration, serum phosphorus concentrations and serum Ca x P values., Results: Sixteen patients received paricalcitol for a mean of 18 months. The mean +/- SD dose of paricalcitol was 0.13 +/- 0.12 mcg/kg. The mean +/- SD pre-paricalcitol serum PTH concentration was 705 +/- 423 pg/mL. PTH concentration did not change significantly over the duration of treatment (mean +/- SD: 821 +/- 480 pg/mL). The number of patients who had at least one corrected serum calcium concentration > or = 11.5 mg/dL, one serum phosphorus concentration > or = 6.5 mg/dL, or one Ca x P level > or = 70 were 75%, 94% and 82%, respectively. Hypercalcemia and elevated Ca x P value resulted in a mean of 17% of doses being withheld during therapy., Conclusion: During the study, PTH was not adequately suppressed by paricalcitol. This was primarily attributed to withholding paricalcitol doses due to elevated serum calcium and Ca x P levels.

Calcium and aluminum phosphate binders are used to treat hyperphosphatemia which is responsible for the development of osteodystrophy commonly seen in patients with end-stage renal disease. The purpose of this study was to determine the phosphate binding capacities of several frequently used calcium and aluminum formulations. The effect of formulation types on phosphate binding was evaluated. Calcium and aluminum phosphate binders were administered to six healthy volunteers after phosphate load on separate study days. Total urine outflow was collected afterwards to determine the amount of phosphate recovered, which indicates the ability of the phosphate binder to reduce gastrointestinal phosphate absorption. The amounts of urinary phosphate recovered were different after administration of the phosphate binders. Calcium acetate resulted in the least amount of phosphate excreted. Calcium carbonate suspension, when compared with the tablet formulation, caused a smaller amount of phosphate excreted in the urine. Different phosphate binders formulations were found to have different phosphate binding capacities. Patients should therefore be closely monitored for efficacy after switching from one phosphate binder to another.

Continuous hemofiltration was conducted in vitro to identify parameters that affect drug transport across hemofilter membranes. The removal of seven drugs with different molecular weights and protein binding characteristics was assessed. Sieving coefficients were determined with both blood and saline using polysulfone, polyacrylonitrile and polyamide membranes. Drug sieving coefficients obtained with saline were generally higher than those obtained with blood. Molecular weights of the drugs did not correlate with the magnitude of drug sieving. Sieving coefficients in blood were also predicted from saline data assuming plasma protein binding is responsible for the reduced drug sieving with blood. For drugs that are highly protein bound, protein binding was the primary factor limiting drug sieving. Presence of plasma proteins also had a modest effect on sieving of other drugs. The sieving coefficients obtained with the polyacrylonitrile membrane tend to be different from those obtained with the other hemofilters. Drug-membrane interaction may contribute to the differences in drug transport among the membranes.

Cephalosporins are used with increasing frequency for sepsis treatment in patients receiving CAVU and CAVH. The different cephalosporins share the same basic molecular structure, yet they exhibit varied extent of plasma protein binding. Different amounts of the antibiotics may be removed by the ultrafiltration procedure because of these variations of physicochemical properties. We evaluated the sieving of eight new cephalosporins across the hemofilter membrane using an in vitro model. Bovine blood was perfused through polysulfone membranes at blood and ultrafiltrate flow rates of 100 and 20 ml/min respectively. Arterial plasma, venous plasma and ultrafiltrate drug concentrations were used to determine sieving coefficients. The sieving coefficients correlated well with the ultrafiltrate-arterial plasma drug concentration ratio (r = 0.679-0.972) but poorly with the extent of protein binding. Factors other than protein binding may therefore affect the drug sieving. Based on the findings, it was predicted that 0.2-21.9% of the daily cephalosporin dose may be removed by the CAVU and CAVH treatment. The need to alter drug dosages depends on the techniques of the ultrafiltration and hemofiltration procedure, the kinetics of the cephalosporins in patients, the sensitivity of the pathogen and the nature of the infection.