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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
1992-3-13
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pubmed:abstractText |
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 (Cavss = 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 greater than or equal to 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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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0041-1337
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
53
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
345-51
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:1738928-Administration, Oral,
pubmed-meshheading:1738928-Adult,
pubmed-meshheading:1738928-Biological Availability,
pubmed-meshheading:1738928-Creatinine,
pubmed-meshheading:1738928-Cyclosporine,
pubmed-meshheading:1738928-Dose-Response Relationship, Drug,
pubmed-meshheading:1738928-Female,
pubmed-meshheading:1738928-Graft Rejection,
pubmed-meshheading:1738928-Humans,
pubmed-meshheading:1738928-Injections, Intravenous,
pubmed-meshheading:1738928-Intestinal Absorption,
pubmed-meshheading:1738928-Kidney Transplantation,
pubmed-meshheading:1738928-Male,
pubmed-meshheading:1738928-Time Factors
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pubmed:year |
1992
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pubmed:articleTitle |
The ability of pretransplant test-dose pharmacokinetic profiles to reduce early adverse events after renal transplantation.
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pubmed:affiliation |
Department of Surgery, University of Texas Medical School, Houston 77030.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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