title: Determination of posaconazole concentration with LC-MS/MS in adult patients with hematologic malignancy.
abstract: BACKGROUND
  Posaconazole has an important role in the prophylaxis of invasive fungal infections (IFIs), however oral suspension formulation is associated with variable bioavailability. The relationship between posaconazole concentrations achieved with the oral suspension and the IFI occurrence were analyzed along with demographic and clinical covariates (mucositis, diarrhea, liver enzymes, co-medications, and food intake).
  
  
  METHODS
  One hundred twenty-two adult patients with AML/MDS undergoing remission induction chemotherapy were enrolled. They received posaconazole as prophylaxis and 557 posaconazole measurements were performed with a validated LC-MS/MS method.
  
  
  RESULTS
  The median (range) posaconazole concentration (ng/ml) on days 2, 3, 7, 14, and 21 was 271 (43-493), 564 (101-1461), 713 (85-2186), 663 (85-1994), and 497 (43-1872), respectively. Thirteen patients (11%) developed proven (1/13), probable (2/13), and possible IFIs (10/13). A significant relationship existed between lower steady-state posaconazole concentrations and a higher breakthrough IFI incidence by binary logistic regression (P=0.0108). Posaconazole value of ≥ 338 ng/ml on day 3 predicted the achievement of ≥ 500 ng/ml at day 7 (sensitivity: 78.5%, specificity: 66.7%, AUC: 0.747). Food intake (P=0.0014) and proton pump inhibitor (P=0.0063) were significantly associated with higher and lower posaconazole concentrations, respectively.
  
  
  CONCLUSIONS
  TDM of posaconazole oral suspension formulation is recommended based on the exposure-response relationship of the present study.
authors: Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; Catholic Laboratory Development and Evaluation Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors: Hyojin
authors: H
authors: Chae
authors: Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors: Sung-Yeon
authors: SY
authors: Cho
authors: Catholic Laboratory Development and Evaluation Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors: Haein
authors: H
authors: Yu
authors: Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors: Kyoungho
authors: K
authors: Cha
authors: Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; Catholic Laboratory Development and Evaluation Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors: Seongok
authors: S
authors: Lee
authors: Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; Catholic Laboratory Development and Evaluation Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. Electronic address: microkim@catholic.ac.kr.
authors: Myungshin
authors: M
authors: Kim
authors: Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; Catholic Laboratory Development and Evaluation Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors: Yonggoo
authors: Y
authors: Kim
authors: Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors: Yoo-Jin
authors: YJ
authors: Kim
authors: Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors: Hee-Je
authors: HJ
authors: Kim
authors: Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors: Dong-Gun
authors: DG
authors: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000097:blood / Q000494:pharmacology; D002853:Chromatography, Liquid; D005260:Female; D019337:Hematologic Neoplasms / Q000097:blood* / Q000150:complications* / Q000382:microbiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000150:complications* / Q000517:prevention & control*; D053719:Tandem Mass Spectrometry; D014230:Triazoles / Q000097:blood* / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D014230:Triazoles; C101425:posaconazole
keywords: Invasive fungal infections; Mass spectrometry; Posaconazole; Prophylaxis; Therapeutic drug monitoring