TY - JOUR
T1 - The ability of pretransplant test-dose pharmacokinetic profiles to reduce early adverse events after renal transplantation
AU - Kahan, Barry D.
AU - Welsh, Maria
AU - Rutzky, Lynne
AU - Lewis, Richard
AU - Knight, Richard
AU - Katz, Stephen
AU - Napoliv, Kim
AU - Grevel, Joachim
AU - Van Buren, Charles T.
PY - 1992/2
Y1 - 1992/2
N2 - 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.
AB - 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.
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U2 - 10.1097/00007890-199202010-00016
DO - 10.1097/00007890-199202010-00016
M3 - Article
C2 - 1738928
AN - SCOPUS:0026551264
SN - 0041-1337
VL - 53
SP - 345
EP - 351
JO - Transplantation
JF - Transplantation
IS - 2
ER -