Hyojin Chae1, Sung-Yeon Cho2, Haein Yu3, Kyoungho Cha4, Seongok Lee1, Myungshin Kim5, Yonggoo Kim1, Yoo-Jin Kim6, Hee-Je Kim6, Dong-Gun Lee7. 1. 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. 2. 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. 3. Catholic Laboratory Development and Evaluation Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. 4. Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. 5. 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. 6. Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. 7. 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.
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.
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: Bart G J Dekkers; Martijn Bakker; Kim C M van der Elst; Marieke G G Sturkenboom; Anette Veringa; Lambert F R Span; Jan-Willem C Alffenaar Journal: Curr Fungal Infect Rep Date: 2016-05-07
Authors: Hyeon Jeong Suh; Inho Kim; Joo Youn Cho; Sang In Park; Seo Hyun Yoon; Jeong Ok Lee; Youngil Koh; Kyoung Ho Song; Pyoeng Gyun Choe; Kyung Sang Yu; Eu Suk Kim; Hong Bin Kim; Soo Mee Bang; Nam Joong Kim; Sang Hoon Song; Wan Beom Park; Myoung Don Oh Journal: Infect Chemother Date: 2017-06-09
Authors: Whitley M Yi; Kelly E Schoeppler; Jaclyn Jaeger; Scott W Mueller; Robert MacLaren; Douglas N Fish; Tyree H Kiser Journal: Ann Clin Microbiol Antimicrob Date: 2017-09-11 Impact factor: 3.944