Browse views: by Year, by Function, by GLF, by Subfunction, by Conference, by Journal

Pharmacokinetics of Sotrastaurin Combined With Tacrolimus or Mycophenolic Acid in De Novo Kidney Transplant Recipients

Kovarik, John M. (2011) Pharmacokinetics of Sotrastaurin Combined With Tacrolimus or Mycophenolic Acid in De Novo Kidney Transplant Recipients. Transplantation, 91 (3). pp. 317-322. ISSN 0041-1337


Background. Sotrastaurin is a protein kinase C inhibitor in the development for prevention of organ rejection after
renal transplantation.
Methods. In a multicenter phase 2 trial, 216 de novo renal transplant recipients were randomized to mycophenolic acid
(MPA) with standard-exposure tacrolimus (treatment A, n74), 200 mg sotrastaurin twice daily with standardexposure
tacrolimus (treatment B, n76), or 200 mg sotrastaurin twice daily with reduced-exposure tacrolimus
(treatment C, n66). After month 3, tacrolimus was replaced with MPA in arms B and C. The longitudinal pharmacokinetics
of sotrastaurin and tacrolimus were prospectively evaluated through month 6.
Results. Sotrastaurin predose drug concentration (C0) was 0.60.4 g/mL and did not differ when combined with
standard-exposure versus reduced-exposure tacrolimus (P0.99) nor when tacrolimus was replaced by MPA
(P0.11). Sotrastaurin peak concentration was 1.60.6 g/mL, and area under the drug concentration-time curve
over a dosing interval (AUC) was 12.24.2 g hr/mL. Intersubject variability in AUC was 27% and not significantly
influenced by age (18–67 years), weight (47–121 kg), sex, or creatinine clearance (36–173 mL/min). Sotrastaurin C0
was positively correlated with AUC (r20.62, P0.0001). Sotrastaurin increased tacrolimus concentrations by a pharmacokinetic
interaction inasmuch as the tacrolimus dose needed to achieve a given C0 was up to 47% lower when
combined with sotrastaurin versus with MPA.
Conclusions. Sotrastaurin pharmacokinetics were similar when combined with reduced-exposure or standard-exposure
tacrolimus or with MPA. Tacrolimus exposure was significantly increased by sotrastaurin in the initial weeks posttransplant
by a pharmacokinetic interaction.

Item Type: Article
Related URLs:
Additional Information: author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used
Related URLs:
Date Deposited: 13 Oct 2015 13:15
Last Modified: 13 Oct 2015 13:15