A nomogram for predicting optimal dosage of cyclosporine in renal transplant patients: taking physiological factors into consideration for regimen during immunosuppressive therapy.
We constructed a nomogram for determining the optimal regimen of cyclosporine (CyA), based on physiological changes that occur during immunosuppressive therapy. The nomogram consists of a fixed model and a variable model. In the fixed model, the oral dose of CyA (D, mg/kg) is given by the multiple linear function of logarithmic CyA trough level (TL, ng/ml), the surrogate apparent total body clearance of CyA (CL/fsu, l/h/kg, being equal to D/TL/12), and the erythrocyte-to-plasma distribution ratio of CyA (CyA-EP), as defined by: D = 4.938 x log(TL) + 1.5037 x CL/fsu - 0.0326 x CyA-EP - 10.7156. In the variable model, the CL/fsu is given by the CyA-EP and the patient's intrinsic parameters (P1, P2), using a nonlinear equation: CL/fsu = P1 x exp(P2 x CyA-EP)/CyA-EP. An optimal CyA dose to maintain a desired trough level was calculated, and the validity of the nomogram was found satisfactory for clinical use. This offers a very concise and practical method for the therapeutic monitoring of CyA. Because the pharmacokinetics of CyA depends on physiological changes due to several disease states, and because the CyA-EP reflects the pharmacokinetics of CyA and the patient's disease state, the proposed nomogram is believed to provide an optimal dosage adjustment, taking physiological factors into consideration.
Shibata
N
N
Department of Hospital Pharmacy, Shiga University of Medical Science, Otsu, Japan.
Hoshino
N
N
Minouchi
T
T
Yamaji
A
A
D000293:Adolescent; D000328:Adult; D002648:Child; D016572:Cyclosporine / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D016231:Fluorescence Polarization Immunoassay; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000502:physiology*; D008111:Liver Function Tests; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D011446:Prospective Studies; D012189:Retrospective Studies
D007166:Immunosuppressive Agents; D016572:Cyclosporine