CYCLOSPORINE-A TROUGH LEVELS CORRELATE WITH SERUM-LIPOPROTEINS AND APOLIPOPROTEINS - IMPLICATIONS FOR THERAPEUTIC DRUG-MONITORING OF CYCLOSPORINE-A

In a prospective study over 6 months, the relationship between serum l ipid parameters and CsA whole blood trough concentrations was investig ated in 39 renal transplant recipients,receiving a triple immunosuppre ssive therapy with cyclosporin (CsA), azathioprine and prednisone. CsA trough concentrations were measured with a selective monoclonal immun oassay (Abbott TDx). Six months after transplantation, significant pos itive correlations were observed between the CsA trough concentration and serum concentrations of triglycerides (r = 0.448, p < 0.01), total cholesterol (r = 0.360, p < 0.05), and apoB (r = 0.418, p < 0.01). Af ter exclusion of patients with overt hypertriglyceridemia (>400 mg/dl) , however, the associations were no longer significant. HDL-cholestero l (HDL-C) and apo AI concentrations showed significant inverse correla tions with the CsA trough level (HDL-C: r = -0.427, p < 0.01; apoAI: r = -0.350, p < 0.05); the correlations with the CsA trough level were still significant (HDL-C: r = -0.379, p < 0.05; apoAI: r = -0.354, p < 0.05) after exclusion of patients with triglyceride levels of >400 mg /dl. As a result of these divergent effects on the plasma lipids and l ipoproteins, there was a strong positive association (r = 0.633, p < 0 .001) between the CsA trough concentration and the total cholesterol/H DL-C ratio. Consequently, elevated total cholesterol/HDL-C ratios that represent an increased atherogenic risk tended to be associated with higher CsA trough levels. In monitoring CsA therapy of renal transplan t recipients on maintenance immunosuppressive therapy, it may well be advisable to adjust CsA dosages to obtain CsA trough levels within the lower therapeutic range for patients with an unfavorably high TC/HDL- C ratio.