Apparent low absorbers of cyclosporine microemulsion have higher requirements for tacrolimus in renal transplantation

A.A. House, M. Elmestiri, K. Denesyk, P.R. Luke, N. Muirhead, F. Rehman, Neil Boudville, A.M. Jevnikar

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    Bioavailability and exposure of cyclosporine microemulsion and tacrolimus in renal transplantation are governed by many complex factors. Failure to achieve therapeutic two-h post-dose (C-2) levels despite adequate doses of cyclosporine ("low absorbers") may merit conversion to tacrolimus. We compared tacrolimus dose requirements in "low absorbers" (n = 15) with a random control group of de novo tacrolimus patients (n = 14). Low absorbers failed to reach target C-2 despite increasing dose from 10.1 to 16.2 mg/kg/d. At conversion the mean C-2 was 969 ng/mL (95% Cl: 684-1255; target 1700 ng/mL). Low absorbers tended to be younger, heavier, and diabetic. Despite a similar initial tacrolimus dose (0.17-0.18 mg/kg/d), low absorbers required a much higher daily dose to achieve target; 0.25 vs. 0.16 mg/kg/d (p = 0.016). Furthermore, daily maintenance tacrolimus remained much higher in low absorbers at three wk (0.22 vs. 0.13 mg/kg/d, p = 0.012). Although not statistically significant, this group experienced an acute rejection rate of 33%, compared with 21% in the control group. Patients treated with cyclosporine as initial immunosuppression who fail to reach target C-2 levels in a timely fashion are at risk for impaired bioavailability of tacrolimus. Based on our data, a starting dose of 0.25 mg/kg/d in divided doses may be warranted for low absorbers converting to tacrolimus; however, we encourage larger studies with formal pharmacokinetic analysis in this population.
    Original languageEnglish
    Pages (from-to)518-522
    JournalClinical Transplantation
    Issue number4
    Publication statusPublished - 2007


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