title: A simple method for predicting the cyclosporin A erythrocyte-to-plasma distribution ratio in blood, and its clinical assessment.
abstract: To adapt the monitoring of cyclosporin A (CyA) to clinical practice, we have developed a model to predict the CyA erythrocyte-to-plasma distribution ratio (CyA-EP), and evaluated its utility in clinical practice. We monitored CyA trough concentrations in whole blood and performed a series of biochemical tests during disease states in patients undergoing immunosuppressive therapy with CyA after transplantation. An estimate of CyA-EP (EPpr) was thus given by the following equation: EPpr = 6.0831 - 0.2944 x (TG+CHO) - 0.0037 x (CyAblood) - 0.0553 x (HCT) + 0.0463 x (BW) + 0.4447 x (CRE) - 0.0366 x (AGE). In this predictive model, EPpr is given as a function of the plasma lipid levels (TG+CHO, mM), the CyA concentration in whole blood (CyAblood, ng/ml), and the hematocrit (HCT, %), as well as the patient's body weight (BW, kg), serum creatinine (CRE, mg/dl) and age (AGE, years). The parameters TG+CHO, CyAblood, HCT, and AGE were negatively correlated with the CyA-EP, whereas BW and CRE exhibited a positive correlation. The predictive performance of this model was satisfactory for clinical use and changes in CyA-EP in transplant patients were obtained from monitoring CyA in whole blood and routine biochemical tests, without directly measuring CyA-EP. Since CyA-EP is an useful indicator for predicting a shift of CyA into tissues and its systemic clearance in plasma, our model to predict the CyA-EP will help the physician select a CyA regimen during immunosuppressive therapy in a variety of disease states after transplantation.
authors.affiliation: Department of Hospital Pharmacy, Shiga University of Medical Science, Otsu, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Shibata
authors.forename: A
authors.initials: A
authors.lastname: Yamaji
authors.forename: K
authors.initials: K
authors.lastname: Park
authors.forename: T
authors.initials: T
authors.lastname: Tomoyoshi
authors.forename: H
authors.initials: H
authors.lastname: Sako
authors.forename: H
authors.initials: H
authors.lastname: Abe
authors.forename: M
authors.initials: M
authors.lastname: Kodama
authors.forename: Y
authors.initials: Y
authors.lastname: Nakane
authors.forename: K
authors.initials: K
authors.lastname: Hodohara
authors.forename: S
authors.initials: S
authors.lastname: Hosoda
mesh_terms: D000328:Adult; D016026:Bone Marrow Transplantation / Q000276:immunology; D016572:Cyclosporine / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D004912:Erythrocytes / Q000378:metabolism*; D005069:Evaluation Studies as Topic; D016231:Fluorescence Polarization Immunoassay; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology; D008954:Models, Biological; D010949:Plasma / Q000737:chemistry; D012044:Regression Analysis
chemical_list: D016572:Cyclosporine