Rapid attainment of target trough concentrations of tacrolimus for early improvement of clinical symptoms in patients with ulcerative colitis. (2nd January 2019)

• Record Type: Journal Article
• Authors: Yamada, Yuto; Ohno, Yuta; Niwa, Takashi; Kato‐Hayashi, Hiroko; Hayashi, Hideki; Ibuka, Takashi; Araki, Hiroshi; Sugiyama, Tadashi; Shimizu, Masahito; Suzuki, Akio
• Is Part Of: Journal of clinical pharmacy and therapeutics. Volume 44:Number 3(2019)
• Page Start: 409
• Page End: 414
• Publication Date: 2019-01-02
• Subjects: administration method -- early improvement -- serum concentration -- tacrolimus; Clinical pharmacology -- Periodicals; Chemotherapy -- Periodicals; 615
• DOI: 10.1111/jcpt.12800
• Languages: English
• ISSNs: 0269-4727

Abstract

Summary: What is known and objective: The target trough concentration of tacrolimus for ulcerative colitis is recommended to be 10‐15 ng/mL in the initial two weeks and 5‐10 ng/mL in the later phase. However, the effectiveness of rapid attainment of these target trough concentrations of tacrolimus in patients with ulcerative colitis is still unclear. In the present study, we evaluated the clinical efficacy and safety of rapid attainment of target trough concentrations of tacrolimus in patients with ulcerative colitis. Methods: A prospective cohort was conducted at Gifu University Hospital in Gifu, Japan. Hospitalized patients who received tacrolimus for the treatment of ulcerative colitis between April 2009 and March 2017 were enrolled. Since June 2011, the initial loading dose of tacrolimus increased from 0.05 to 0.1‐0.2 mg/kg/d, and the maintenance dose to achieve the target trough concentration was determined to be 12.5 ng/mL by proportional calculation with measured blood concentration. The period required to attain target trough concentration and the clinical efficacy before and after dosage modification was compared. Results: The initial dose after dosage modification was significantly increased compared to that before dosage modification (0.10 [0.04‐0.22], median [range] mg/kg/d vs 0.05 [0.03‐0.05] mg/kg/d, P < 0.001). The period required to attain a target trough concentration over 10 ng/mL was significantly shortened by dosage modification (6 [4‐14] days before dosage modification vs 4.5 [2‐8] days after modification, P = 0.048). Further, stool frequency score was significantly improved after dosage modification, without affecting the incidence of adverse events. What is new and conclusion: Our findings suggest that rapid attainment of the target trough concentration of tacrolimus improves clinical symptoms in patients with ulcerative colitis. Abstract : We modified the administration method of tacrolimus for ulcerative colitis with the aim of rapidly attaining the high trough level of 10–15 ng/mL. As the result, the period required to attain a target trough concentration over 10 ng/mL was significantly shortened by dosage modification (6 [4–14] days before dosage modification vs 4.5 [2–8] days after modification, P = 0.048). Moreover, stool frequency score was significantly improved after dosage modification, without affecting the incidence of adverse events.