Population pharmacokinetics of sirolimus in kidney transplant patients

摘要: Objective To characterize the dose-related pharmacokinetics of immunosuppressant agent sirolimus (formerly rapamycin) in kidney transplant patients by use two-stage and nonlinear mixed-effect model population methods. Methods Patients (n = 36) from three centers (Germany, United Kingdom, Sweden) who received steady-state oral doses cyclosporine (ciclosporin) were assessed after single administration at 3, 5, 10, 15 mg/m2. Plasma whole blood samples analyzed a high-performance liquid chromatographic/mass spectrophotometric method. Simultaneous fitting used biexponential functions with intercept/slope or clearance/volume terms, as well first-order absorption (ka) lag-time. Results The method (P-Pharm) provided better characterization kinetics, especially for distribution phases where fewer data available per patient. Sirolimus between plasma was concentration-independent, mean blood/plasma ratio (coefficient variation) 30.9 (48.5%). Elimination not influenced dose, shown estimates terminal half-life 63 hours (27.5%) apparent clearance 8.9 L/hr (38.2%). parameters body weight surface area. rapidly absorbed, lag-time 0.27 hour (35.1%), ka 2.77 hr−1 (48.4%). The concomitant did reveal any pharmacokinetic interaction. Conclusion This report provides an initial recipients receiving concurrently. linear 3 to No interaction found cyclosporine. Clinical Pharmacology & Therapeutics (1997) 61, 416–428; doi: