Experience with cyclosporine

Abstract

The concentration at 2 hours after drug intake (C2) is proposed to optimise clinical outcomes in organ transplantation and for adjustment of the regimen of cyclosporine. A population based pharmacokinetic study was undertaken during the first 30 days post-liver transplantation. Preliminary results observed during this study on C0 and C2 values are described here. Thirty-seven patients with first hepatic transplantation were included in a single center, prospective study conducted under conditions of normal practice. Dose adjustments were made according to C0. Cyclosporine C0 and C2 were assayed by an immunoassay (EMIT) and by a HPLC technique. Clinical outcome was assessed by occurrence and severity of acute rejection. Our data shows that average blood C0 and C2 concentrations are significantly different with the two techniques. From the third day to the end of the study, mean C2 (EMIT) were within or near the recommended values. This was associated with a low rejection rate (8.8%). Nevertheless, individual values are largely dispersed and low cyclosporine absorption profiles are identified. Mean cyclosporine dose was low compared to a previous study (7.65 ± 4.28 mg/kg/day). Our data suggest that the target ranges need to be adjusted when different techniques are applied and that optimal cyclosporine regimen to achieve the C2 goal and low rejection rate remains to be defined. Pharmacokinetic models based on population study are needed to describe normal and abnormal cyclosporine absorption profiles with higher accuracy.