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Tacrolimus blood concentration increase depends on administration route when combined with voriconazole in pediatric stem cell transplant recipients
Author(s) -
Utano Tomoyuki,
Kato Motohiro,
Osumi Tomoo,
Shioda Yoko,
Kiyotani Chikako,
Terashima Keita,
Tomizawa Daisuke,
Matsumoto Kimikazu,
Yamatani Akimasa
Publication year - 2020
Publication title -
pediatric transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.457
H-Index - 69
eISSN - 1399-3046
pISSN - 1397-3142
DOI - 10.1111/petr.13619
Subject(s) - medicine , concomitant , transplantation , pharmacokinetics , tacrolimus , voriconazole , pharmacology , urology , antifungal , dermatology
Background Understanding of TAC pharmacokinetics is required to avoid both overdosing and underdosing. VRCZ is known to increase the TAC blood concentration by inhibiting CYP3A4; however, detailed, practical information on pediatric cases is still scarce. Herein, we investigated the association between the TAC blood concentration and dosage focusing on the administration route and concomitant use of VRCZ in children. Methods In total, 38 children who received TAC during stem cell transplantation at our hospital between January 2013 and April 2018 were included. The ratio of the TAC blood concentration (ng/mL) to dosage (mg/kg/day) (C/D) was calculated at the last continuous intravenous infusion (C/Div) and after switching to oral administration (C/Dpo). Results Patients with VRCZ (n = 14) showed a higher C/D regardless of administration route (median C/Div: with VRCZ/without VRCZ = 832/643, median C/Dpo: with VRCZ/without VRCZ = 339/45). Additionally, the (C/Div)/(C/Dpo) was about one‐fourth in cases with VRCZ; the median (C/Div)/(C/Dpo) was 3.3 for cases with VRCZ and 13.5 for cases without VRCZ. Interestingly, the increase in the TAC blood concentration due to VRCZ was higher when TAC was administered orally, especially in adolescent patients. Conclusions To obtain an optimal TAC blood concentration, dose adjustment based on multiple factors, such as administration route, concomitant use of VRCZ, and age, is required.