The ability of pretransplant test-dose pharmacokinetic profiles to reduce early adverse events after renal transplantation

Barry D. Kahan, Maria Welsh, Lynne Rutzky, Richard Lewis, Richard Knight, Stephen Katz, Kim Napoliv, Joachim Grevel, Charles T. Van Buren

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

Pretransplant test-dose pharmacokinetic profiles were used to determine individual cyclosporine drug bioavailability and clearance rates in renal transplant patients. Assuming a linear relation between dose and area under the concentration curve (AUC), starting i.v. and p.o. CsA doses were computed from the test-dose results. Target values were 400 ng/ml steady-state concentration (Css) during continuous intravenous infusion, and 500 ng/ml average drug concentration (Cav(ss) = AUC/dosing interval) after oral administration, based upon measurements with the specific monoclonal antibody 3H-tracer radioimmunoassay. The outcomes after dose individualization with a 1-(n=32), 2-(n=38), or 3-(n=41) hr i.v. infusion test dose and a p.o. test dose (n=111) were compared with 228 historical control patients who received a uniform protocol of CsA i.v. at 2.5 mg/kg/day and p.o. at 14 mg/kg/day. The observed Css after i.v. CsA was within 10% of the target concentration in 73% of recipients tested with the 3-hr protocol, a significantly greater fraction than achieved with either the uniform dose (14%), or the 1-(34%) and 2-(25%) hr protocols. Patients in the 3-hr protocol group showed reduced incidences of delayed graft function, early graft loss, and rejection episodes, and a lower mean serum creatinine value, particularly at 7 but also at 30 days posttransplantation. Administration of the predicted oral dose produced a peak concentration of ≥700 ng/ml drug absorption in 60% of recipients at 3 days, 90% at 5 days, and 98% at 7 days. The test-dose method less effectively predicted the appropriate oral CsA dose to produce target Cssav and failed to reduce the 90-day rejection incidence. Despite its limitations with the more- complicated p.o. route, the test-dose method successfully predicts i.v. CsA doses, thereby reducing the incidence of early adverse events.

Original languageEnglish (US)
Pages (from-to)345-351
Number of pages7
JournalTransplantation
Volume53
Issue number2
DOIs
StatePublished - Feb 1992

ASJC Scopus subject areas

  • Transplantation

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