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Apparent low absorbers of cyclosporine microemulsion have higher requirements for tacrolimus in renal transplantation
Author(s) -
House Andrew A.,
Elmestiri Mostafa,
Denesyk Kathy,
Luke Patrick P.,
Muirhead Norman,
Rehman Faisal,
Boudville Neil,
Jevnikar Anthony M.
Publication year - 2007
Publication title -
clinical transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 76
eISSN - 1399-0012
pISSN - 0902-0063
DOI - 10.1111/j.1399-0012.2007.00680.x
Subject(s) - tacrolimus , medicine , bioavailability , immunosuppression , urology , transplantation , pharmacokinetics , population , pharmacology , environmental health
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% CI: 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.