House AA et al. (2007) Apparent low absorbers of cyclosporine microemulsion have higher requirements for tacrolimus in renal transplantation. Clin Transplant 21: 518–522

Some kidney transplant recipients who receive initially adequate doses of ciclosporin fail to achieve therapeutic 2 h post-dose (C2) levels of this calcineurin inhibitor. One option in such cases is to switch patients to tacrolimus, which has a different pharmacokinetic profile. As the absorption rate ratios of the two drugs are, however, almost identical, a Canadian group has investigated whether 'converted' patients require higher tacrolimus doses than do de novo tacrolimus patients.

House et al. retrospectively identified 15 adult recipients of a first renal transplant who were converted from ciclosporin to tacrolimus (plus mycophenolate mofetil and steroids). These patients had failed to reach target C2 levels of ciclosporin despite dose increases, and were switched to tacrolimus a mean 5.1 days after transplantation. This group was compared with a group of 14 control patients treated initially with tacrolimus. Initial tacrolimus dosages were similar in the conversion and de novo groups (0.18 and 0.17 mg/kg/day, respectively), but converted patients required higher daily doses to achieve target trough levels (0.25 vs 0.16 mg/kg/day, P = 0.016; target 10–15 ng/ml). At 3 weeks, maintenance tacrolimus doses remained significantly higher in low ciclosporin absorbers than in the control patients (0.22 vs 0.13 mg/kg/day; P = 0.012). The rate of acute rejection tended to be higher in converted patients than in controls (33% vs 21%).

The authors suggest that patients who switch to tacrolimus because of failure to reach target C2 ciclosporin levels should receive a high initial dosage (e.g. 0.25 mg/kg/day) of this immunosuppressive agent.