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Cyclosporine is associated with lower hospitalization costs for transplantation of cadaver kidneys. Whether this cost-lowering effect persists after discharge was assessed for 203 patients who received cadaver kidneys at the University of California, San Francisco, between July 1982 and June 1986. During the transplantation hospitalization period, cyclosporine was associated with significantly better graft survival (88.7% vs 71.0%) and lower (standardized) costs ($37,174 vs $52,983). Following discharge, however, there were no significant differences in graft survival, total charges ($29,716 vs $34,434), the number of readmissions, the total number of days hospitalized, or physician charges, although cyclosporine was associated with higher drug costs ($3885 vs $373). The results suggest that the initial association of cyclosporine with lower costs diminished substantially over time. For grafts that survive beyond several months, there may be little additional cost-reducing benefits of cyclosporine. [ABSTRACT FROM AUTHOR]

The impact of nonlinear plasma protein binding of a drug on its removal by haemodialysis has been quantified. Prednisolone 10-100 mg was given i.v. to 10 renal transplant patients on haemodialysis for acute tubular necrosis. Dialysate and afferent and efferent blood samples were collected simultaneously in 67 instances. Total and unbound prednisolone in plasma and its total concentration in blood and dialysate were assessed by high performance liquid chromatography and equilibrium dialysis. The amount of prednisolone lost, as measured directly in the dialysate (21.8±4.4 µg/min, $${{\bar x}}$$ ± SE), was predictable from the afferent-efferent blood concentration differences (20.1±4.8 µg/min), but not from measurements of total afferent-efferent prednisolone concentrations in plasma (13.1±3.0 µg/min). The amount of prednisolone lost in the dialysate increased linearly with unbound ( r=0.96) and hyperbolically with the total prednisolone concentration in plasma. The latter hyperbolic relationship is adequately described by the equation for nonlinear plasma protein binding, using the affinity and capacity constants of albumin and transcortin for prednisolone ( r=0.98). Thus, the haemodialysis clearance of total prednisolone is concentration-dependent, while the clearance of unbound prednisolone is constant (76 ml/min). Free clearance values or measurements of afferent-efferent blood concentrations are mandatory for a drug showing nonlinear plasma protein binding in order to predict the amount lost in the dialysate. [ABSTRACT FROM AUTHOR]

To establish if the appearance of cushingoid side effects in patients taking exogenous glucocorticoids is related to the disposition and metabolism of these steroids and endogenous hydrocortisone, 15 stable renal transplant patients and 12 patients treated with prednisone for oral mucocutaneous vesiculo-erosive diseases were investigated. All 27 patients were given their usual prednisone dose orally on one occasion, and 24 were given the same amount of prednisolone intravenously on another occasion. Following dosing, plasma samples were obtained for determination of the areas under the plasma concentration time curves of total prednisolone, prednisone and hydrocortisone by high performance liquid chromatography, and of unbound prednisolone by equilibrium dialysis. The bioavailability of prednisone, the interconversion of prednisone into prednisolone, the clearance of total and unbound prednisolone, the prednisolone binding capacity of albumin and transcortin, and the affinity of albumin for prednisolone did not differ between the 14 patients without cushingoid side effects and the 13 cushingoid patients. Compared to those who had cushingoid features, patients who developed no side effects had a higher affinity constant for prednisolone binding to transcortin − 2.04±0.27 × 10 L/M vs. 1.34±0.16×10 (X±SE; P<0.05), more frequently exhibited peak hydrocortisone levels within the normal range (6/14 vs 1/13), more often had measurable (>10ng/ml) hydrocortisone in the plasma samples collected during the kinetic studies (123/291 vs 74/325; P<0.001) and had higher areas under the plasma concentration time curve of hydrocortisone (median, range), i.e. 8081 ng/ml · min (0-21 637 ng/ml · min) vs 386 ng/ml · min (0-16 329 ng/ml · min; P<0.005). The data suggest that endogenous hydrocortisone production is not as suppressed in patients with visible cushingoid signs as in noncushingoid patients, and that there is no significant difference in the pharmacokinetics of exogenous glucocorticoids between patients with and without cushingoid side effects. [ABSTRACT FROM AUTHOR]