We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Apparent low absorbers of cyclosporine microemulsion have higher requirements for tacrolimus in renal transplantation.
- Authors
House, Andrew A.; Elmestiri, Mostafa; Denesyk, Kathy; Luke, Patrick P.; Muirhead, Norman; Rehman, Faisal; Boudville, Neil; Jevnikar, Anthony M.
- Abstract
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 (C2) 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 C2 despite increasing dose from 10.1 to 16.2 mg/kg/d. At conversion the mean C2 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 C2 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.
- Subjects
BIOAVAILABILITY; CYCLOSPORINE; TACROLIMUS; KIDNEY transplantation; IMMUNOSUPPRESSIVE agents; GRAFT rejection
- Publication
Clinical Transplantation, 2007, Vol 21, Issue 4, p518
- ISSN
0902-0063
- Publication type
Article
- DOI
10.1111/j.1399-0012.2007.00680.x