비만 환자의 조혈모세포이식 후 체중 적용 기준에 따른 Cyclosporine 초기 농도 비교

Abstract

Cyclosporine is the most common immunosuppressant agent against graft-versus-hostdisease (GVHD) in patients with hematopoietic stem cell transplantation (HSCT). The therapeuticrange of cyclosporine is narrow, and there is significant inter-individual and intra-individual variabilityin the pharmacokinetics of the drug. Therefore, therapeutic drug monitoring of cyclosporine isessential to optimize immunosuppressant therapy. In Seoul St. Mary’s hospital, the dose ofcyclosporine is based on the actual body weight. Cyclosporine 5 mg/kg/day is given the day beforeHSCT by 24hrs intravenous infusion. The dose is then changed to 3 mg/kg/day after HSCT. We conductedtherapeutic drug monitoring for the optimal therapeutic range of cyclosporine. The concentrationof cyclosporine is often higher for obese patients than the initial therapeutic range of200~300 ng/ml. As a result, obese patients have a greater risk of cyclosporine side effects than nonobese patients. We evaluated the effects of cyclosporine at an initial dose based on ideal body weightin obese patients. We retrospectively collected the data from obese patients (actual body weight > 120% ideal bodyweight) who received cyclosporine therapy after HSCT, at the Catholic BMT (blood and marrowtransplantation) center from April 2009 to September 2011. Pharmacokinetic parameters were calculatedfrom data collected from monitored patient profiles and actual blood concentration ofcyclosporine. We subsequently calculated the concentration of cyclosporine, according to the dosebased on ideal body weight. Out of 32 patients who received cyclosporine therapy after HSCT, 1 patient who receivedcyclosporine based on actual body weight reached the therapeutic range (3.1%). However, 7 patientswho received cyclosporine based on ideal body weight reached the therapeutic range (21.9%). Theresults showed a significant difference (p=0.014). The median gap between the actual blood concentrationand the upper limit of therapeutic range was 164.1 (-25.3~440.0) ng/ml in patients whoreceived cyclosporine based on actual body weight. The median gap between the calculated bloodconcentration and the upper limit of therapeutic range was 67.7 (-74.0~239.0) ng/ml in patients whoreceived cyclosporine based on ideal body weight. The blood concentration of cyclosporine based onideal body weight was indicative of a more efficient approach to a therapeutic range of cyclosporine. In conclusion, this study suggested that the administration of cyclosporine based on ideal bodyweight might lead to optimal blood concentration and a reduction in cyclosporine side effects. Thecurrent observation needs to be confirmed by prospective investigation in order to determine appropriatecyclosporine therapy in obese patients.