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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Tacrolimus pharmacokinetics of once-versus twice-daily formulations in de novo kidney transplantation: A substudy of a randomized phase III trial
Therapeutic Drug Monitoring, Volume 34, No. 2, Year 2012
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Description
Background: Tacrolimus is a well-established immunosuppressive agent for the treatment and prevention of solid organ graft rejection. It is available as an immediate-release, twice-daily formulation (Tacrolimus BID) and a prolonged-release, once-daily formulation (Tacrolimus QD). In a previous study of the pharmacokinetics (PK) of these formulations, mean systemic exposure [area under the curve from 0 to 24 hours (AUC0-24)] of tacrolimus on day 1 was approximately 30% lower for Tacrolimus QD than for Tacrolimus BID; by day 14, systemic exposure was similar; however, the mean dose of Tacrolimus QD was higher to achieve similar systemic exposure as Tacrolimus BID. Methods: To further compare the PK of the tacrolimus formulations during the first 2 weeks posttransplant, a substudy was performed in a subset of patients enrolled into a phase III trial in de novo kidney transplant recipients comparing Tacrolimus QD and Tacrolimus BID. To minimize the difference in exposure observed in the earlier study, tacrolimus therapy was initiated before transplant. The PK analysis set comprised 34 patients (17 patients per treatment group) who had 4 complete PK profiles and no major PK-related protocol violations. Results: Mean AUC 0-24 of tacrolimus on day 1 was approximately 16% lower for Tacrolimus QD than for Tacrolimus BID, although by day 3 onward, the exposure was similar between treatment groups. Analysis of dose-normalized AUC0-24 (dose normalized to 0.1 mg/kg) showed a similar pattern. There was a good correlation between AUC0-24 and concentration of tacrolimus at 24 hours postdose for both formulations (Tacrolimus QD, r = 0.87; Tacrolimus BID, r = 0.92), and the slope of the line of best fit was similar. Conclusions: These results suggest that initiating tacrolimus therapy before transplant reduces the difference in exposure between Tacrolimus QD and Tacrolimus BID. © 2012 Lippincott Williams & Wilkins.
Authors & Co-Authors
Wlodarczyk, Zbigniew
Poland, Bydgoszcz
Antoni Jurasz University Hospital
Ostrowski, Marek
Poland, Szczecin
General and Transplantology Surgery
Mourad, Michel
Belgium, Brussels
Cliniques Universitaires Saint-luc
Krämer, Bernhard Karl
Germany, Mannheim
Universitätsklinikum Mannheim
Germany, Regensburg
Klinikum Der Universität Regensburg Und Medizinische Fakultät
Abramowicz, Daniel
Belgium, Brussels
Hôpital Erasme
Oppenheimer, Frederico
Spain, Barcelona
Hospital Clinic Barcelona
Miller, Derek
South Africa, Cape Town
Christiaan Barnard Memorial Hospital
Dickinson, James
Netherlands, Leiden
Astellas Pharma B.v.
Undre, Nasrullah A.
United Kingdom, Addlestone
Astellas Pharma Ltd
Statistics
Citations: 23
Authors: 9
Affiliations: 10
Identifiers
Doi:
10.1097/FTD.0b013e31824d1620
ISSN:
01634356
e-ISSN:
15363694