title: Different effects of lansoprazole and rabeprazole on the plasma voriconazole trough levels in allogeneic hematopoietic cell transplant recipients.
abstract: Voriconazole (VRC) is widely used as prophylaxis and in the treatment of invasive fungal disease (IFD) after allogeneic hematopoietic cell transplantation (HCT). We retrospectively examined the results of VRC therapeutic drug monitoring (TDM) in allogeneic HCT recipients. A total of 474 samples were obtained from 59 adult patients who received VRC during the first 100 days following HCT between 2009 and 2014 in our institute. Seventeen patients received VRC for prophylaxis of IFD, and 42 received VRC for the empirical or preemptive therapy for IFD. A total of 299 samples (63 %) were obtained during the administration of the intravenous form of VRC. The median VRC daily dose based on the actual body weight was 6.68 mg/kg/day (range, 1.92-10.41 mg/kg/day). The median VRC trough level was 0.99 mg/l (range, <0.09-5.45 mg/l). The multivariate analysis using a logistic regression model demonstrated significantly higher VRC trough levels (≥1.0 mg/l) in males (P < 0.001), empirical or preemptive therapy (P = 0.002), VRC daily dose based on the actual body weight ≥7 mg/kg/day (P < 0.001), and concomitant use of lansoprazole as compared to rabeprazole (P < 0.001). The concomitant use of calcineurin inhibitors and corticosteroids had no effects on VRC trough levels in multivariate analysis. These data suggest that lansoprazole and rabeprazole have different effects on the plasma VRC trough levels in the allogeneic HCT recipients.
authors.affiliation: Department of Pharmacy, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Yasu
authors.affiliation: Department of Hematology/Oncology, The Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan. tkonuma@ims.u-tokyo.ac.jp.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Konuma
authors.affiliation: Department of Hematology/Oncology, The Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
authors.forename: Seiko
authors.initials: S
authors.lastname: Kato
authors.affiliation: Department of Pharmacy, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Kurokawa
authors.affiliation: Department of Hematology/Oncology, The Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Department of Hematology/Oncology, The Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
authors.forename: Arinobu
authors.initials: A
authors.lastname: Tojo
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001835:Body Weight; D016026:Bone Marrow Transplantation; D036101:Cord Blood Stem Cell Transplantation; D004347:Drug Interactions; D016903:Drug Monitoring; D005260:Female; D019337:Hematologic Neoplasms / Q000097:blood / Q000628:therapy; D006801:Humans; D007275:Injections, Intravenous; D064747:Lansoprazole / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000517:prevention & control; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000628:therapy; D011183:Postoperative Complications / Q000517:prevention & control; D064750:Rabeprazole / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D012189:Retrospective Studies; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous; D065819:Voriconazole / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D064747:Lansoprazole; D064750:Rabeprazole; D065819:Voriconazole
keywords: Allogeneic hematopoietic stem cell transplantation; Invasive fungal disease; Lansoprazole; Rabeprazole; Therapeutic drug monitoring; Voriconazole