Original Research
Comparison of CYP3A5*3 genotyping assays for personalizing immunosuppressive therapy in heart transplant patients
Takaya Uno, Kyoichi Wada, Sachi Matsuda, Yuka Terada, Akira Oita, Mitsutaka Takada, Masanobu Yanase, and Norihide Fukushima
Price
42.00 $
Volume 57 (2019) p. 315 - 322
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 57 – No. 6/2019 (315-322)
Comparison of CYP3A5*3 genotyping assays for personalizing immunosuppressive therapy in heart transplant patients
Takaya Uno1#2#3, Kyoichi Wada1#3, Sachi Matsuda1, Yuka Terada1#3, Akira Oita1, Mitsutaka Takada2#3, Masanobu Yanase4, and Norihide Fukushima4
1Department of Pharmacy, National Cerebral and Cardiovascular Center, 2Division of Clinical Drug Informatics, Faculty of Pharmacy, 3Division of Cardiovascular Drugs, Therapy, Kindai University Graduate School of Pharmacy, and 4Department of Transplant Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan
Objective: This study aimed to compare a novel point-of-care assay that involves a flap endonuclease reaction performed using GTS-7000® to a conventional assay that involves DNA sequencing performed using 3130xl Genetic Analyzers*. Materials and methods: This study enrolled 74 patients who underwent heart transplantation at the National Cerebral and Cardiovascular Center between May 2004 and October 2016. Each patient was genotyped as cytochrome P450 (CYP) 3A5*1/*1, CYP3A5*1/*3, or CYP3A5*3/*3. Quantitative and qualitative comparison between the two assays was carried out. Results: Four patients were genotyped as CYP3A5*1/*1, 25 as CYP3A5*1/*3, and 45 as CYP3A5*3/*3. Genotyping results of the point-of-care method were completely consistent with those of the conventional method. The total analysis time of the point-of-care method was shorter than that of the conventional method (~ 1.5 vs. 7.5 h). However, the cost of the point-of-care method was higher than that of the conventional method (~ 21 vs. 17 US$). Conclusion: Compared with a laboratory-based assay, the point-of-care assay that utilizes GTS-7000® is accurate and rapid despite being slightly more expensive. Further trials using this assay are warranted.Correspondence to:
Norihide Fukushima, PhD
Department of Transplant Medicine
National Cerebral and Cardiovascular Center
5-7-1, Fujishirodai, Suita, Osaka, 565-8565, Japan
Email: [email protected]
Original
Discontinuation of oral amphotericin B therapy does not influence the pharmacokinetics of tacrolimus in heart transplant patients
Megumi Ikura, Tsutomu Nakamura, Takaya Uno, Kazuki Nakagita, Hiromi Takenaka, Sachi Matsuda, Ryosuke Oda, Kyoichi Wada, Yuji Hattori, Osamu Seguchi, Masanobu Yanase, Naoki Hayakawa, and Norihide Fukushima
Price
42.00 $
Volume 59 (2021) p. 566 - 571
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 59 – No. 8/2021 (566-571)
Discontinuation of oral amphotericin B therapy does not influence the pharmacokinetics of tacrolimus in heart transplant patients
Megumi Ikura1, Tsutomu Nakamura2, Takaya Uno1, Kazuki Nakagita1, Hiromi Takenaka1, Sachi Matsuda1, Ryosuke Oda1, Kyoichi Wada2, Yuji Hattori1, Osamu Seguchi3, Masanobu Yanase3, Naoki Hayakawa1, and Norihide Fukushima3
1Department of Pharmacy, National Cerebral and Cardiovascular Center, Suita, 2Education and Research Center for Clinical Pharmacy, Osaka University of Pharmaceutical Sciences, Takatsuki, and 3Department of Transplant Medicine, National Cerebral and Cardiovascular Center, Suita, Japan
Objective: Amphotericin B (AMPH-B) is used to prevent opportunistic infections associated with immunosuppressive therapy after heart transplantation (HTx), while the blood concentrations of tacrolimus (TAC) are carefully controlled. Although AMPH-B has the potential to inhibit TAC metabolism in in vitro studies, its interaction with clinically used AMPH-B oral suspension has not been investigated. In the present study, we examined whether oral AMPH-B therapy influences the pharmacokinetics of TAC in HTx patients.
Materials and methods: A retrospective study was performed at the National Cerebral and Cardiovascular Center in Japan. All patients with HTx enrolled in the study received standard triple-drug immunosuppression therapy including the regular release of TAC, mycophenolate mofetil, and prednisolone as well as prophylactic therapy with AMPH-B oral suspension. Patient characteristics and clinical laboratory data were collected from the electronic medical record system. Blood concentrations of TAC were used for pharmacokinetic analysis.
Results: A total of 14 patients were enrolled in the study. There were no statistically significant differences in the variables except for serum creatinine levels and eGFR before and after discontinuation of oral AMPH-B therapy. The dose and trough concentrations of TAC and the area under the time-concentration curve and apparent oral clearance calculated from its concentrations were not influenced by discontinuation of AMPH-B treatment.
Conclusion: The prophylactic treatment with AMPH-B oral suspension did not influence the pharmacokinetics of TAC and was demonstrated as a safe and easy method to prevent early post-HTx fungal infection.Correspondence to:
Tsutomu Nakamura, PhD, Professor
Education and Research Center for Clinical Pharmacy
Faculty of Pharmacy, Osaka Medical and Pharmaceutical University
4-20-1 Nasahara, Takatsuki 569-1094, Japan
Email: [email protected]
Case
Report
Pharmacokinetics and pharmacodynamics of amiodarone in patients with hypertriglyceridemia: Two case reports
Takaya Uno, Kota Sakakura, Yutaro Mukai, Mitsutaka Takada, Takashi Noda, Kengo Kusano, and Naoki Hayakawa
Price
42.00 $
Volume 60 (2022) p. 515 - 520
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 60 – No. 12/2022 (515-520)
Pharmacokinetics and pharmacodynamics of amiodarone in patients with hypertriglyceridemia: Two case reports
Takaya Uno1#2, Kota Sakakura1, Yutaro Mukai1, Mitsutaka Takada2, Takashi Noda3#4, Kengo Kusano4, and Naoki Hayakawa1
1Department of Pharmacy, National Cerebral and Cardiovascular Center, Suita, 2Division of Clinical Drug Informatics, Faculty of Pharmacy, Kindai University, Higashi-Osaka, 3Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, and 4Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan
Background: The antiarrhythmic drug amiodarone has noncardiac adverse effects, leading to restrictive therapeutic plasma ranges. Despite the significant positive correlation between triglyceride and amiodarone levels, the effect of fluctuations in amiodarone levels in patients with hypertriglyceridemia on amiodarone therapy has not been fully characterized. This study is the first to report on the effect of hypertriglyceridemia on the efficacy and safety of amiodarone therapy.
Case presentation: The first patient was a 58-year-old man with hypertriglyceridemia who was diagnosed with ventricular fibrillation (patient #1). The second patient with hypertriglyceridemia was a 72-year-old man with sustained ventricular tachycardia (patient #2). Both patients received implantable cardioverter-defibrillator therapy. During the study period, amiodarone and N-desethylamiodarone concentrations were measured 12 times in patient #1 and 26 times in patient #2. Triglyceride concentrations in patient #1 and patient #2 ranged from 102 to 765 mg/dL and from 125 to 752 mg/dL, respectively. For both patients, amiodarone dosage was maintained at 100 mg/day, and the administration of concomitant drugs that could affect amiodarone pharmacokinetics was neither initiated nor discontinued. However, amiodarone concentrations fluctuated (patient #1, 0.52 – 1.86 μg/mL; patient #2, 0.73 – 2.82 μg/mL). Although amiodarone concentrations fluctuated, neither of the patients had defibrillation shocks to stop the abnormal rhythm via an implantable cardioverter-defibrillator, and laboratory data showed that thyroid-stimulating hormone, free thyroxine, KL-6, and surfactant protein-D remained close to normal.
Conclusion: In patients with hypertriglyceridemia, it may be necessary for clinicians to pay more attention to the clinical symptoms along with fluctuations in amiodarone levels and accordingly adjust amiodarone dosage.Correspondence to:
Takaya Uno, PhD
Department of Pharmacy
National Cerebral and Cardiovascular Center
564-8565, Suita, Osaka, Japan
Email: [email protected]
Original
Effect of mammalian-target-ofrapamycin inhibitors on the cancer risk in patients receiving calcineurin inhibitors: Data mining of a spontaneous reporting database
Takaya Uno, Mitsutaka Takada, Satoshi Yokoyama, Kazuyoshi Kawabata, and Kouichi Hosomi
Price
42.00 $
Volume 60 (2022) p. 477 - 485
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 60 – No. 11/2022 (477-485)
Effect of mammalian-target-ofrapamycin inhibitors on the cancer risk in patients receiving calcineurin inhibitors: Data mining of a spontaneous reporting database
Takaya Uno1#2, Mitsutaka Takada2, Satoshi Yokoyama2, Kazuyoshi Kawabata1, and Kouichi Hosomi2
1Department of Pharmacy, National Cerebral and Cardiovascular Center, Suita, and 2Division of Clinical Drug Informatics, Faculty of Pharmacy, Kindai University, Higashi-Osaka, Japan
Objective: Calcineurin inhibitors (CNIs), including cyclosporine and tacrolimus, are associated with an increased cancer risk. However, whether mammalian target of rapamycin inhibitors (mTORis), including sirolimus and everolimus, decrease the cancer risk in patients receiving CNIs remains uncertain. We aimed to determine whether mTORis are associated with a decreased cancer risk in patients receiving CNIs using data mining of a spontaneous adverse reaction database.
Materials and methods: Disproportionality analysis was conducted using the U.S. Food and Drug Administration Adverse Event Reporting System database (2004 – 2019) with reporting odds ratio and information component being used to indicate a signal.
Results: Data subset analyses indicated that sirolimus and everolimus were not associated with a decreased cancer risk in patients receiving cyclosporine or tacrolimus but were associated with an increased risk of nonmelanoma skin cancer (NMSC) and Kaposi’s sarcoma.
Conclusion: mTORis are not associated with a decreased cancer risk but are associated with a further increase in the risk of NMSC and Kaposi’s sarcoma in patients receiving CNIs. Further studies are necessary to clarify the mechanism underlying the association between mTORis and NMSC or Kaposi’s sarcoma.Correspondence to:
Takaya Uno, PhD
Department of Pharmacy
National Cerebral and Cardiovascular Center
564-8565, Suita, Osaka, Japan
Email: [email protected]
Original
Trends in tolvaptan prescription and the association between hypernatremia and aging in tolvaptan-treated patients in Japan: Real-world data mining using Japanese databases
Takaya Uno, Kouichi Hosomi, Satoshi Yokoyama, and Kazuyoshi Kawabata
Price
42.00 $
Volume 61 (2023) p. 33 - 36
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 61 – No. 1/2023 (33-36)
Trends in tolvaptan prescription and the association between hypernatremia and aging in tolvaptan-treated patients in Japan: Real-world data mining using Japanese databases
Takaya Uno1#2, Kouichi Hosomi2, Satoshi Yokoyama2, and Kazuyoshi Kawabata1
1Department of Pharmacy, National Cerebral and Cardiovascular Center, Suita, and 2Division of Clinical Drug Informatics, Faculty of Pharmacy, Kindai University, Higashi-Osaka, Japan
Objective: To identify the trends in tolvaptan prescription and the association between aging and tolvaptan-induced hypernatremia.
Materials and methods: A health insurance claims database and a spontaneous adverse drug reaction database were used.
Results: Of all patients who had been prescribed tolvaptan, the proportion of patients aged 60 – 79 years and ≥ 80 years was consistent at ~ 40%. Moreover, the prescription frequency of tolvaptan increased over time for patients in the same age groups. The adjusted reporting odds ratio of tolvaptan-induced hypernatremia was 5.54 (95% confidence interval, 3.31 – 9.25) in patients aged ≥ 60 years from among all patients and 2.09 (95% confidence interval, 1.59 – 2.75) in those aged ≥ 80 years from among those aged ≥ 60 years.
Conclusion: It may be necessary to be aware of hypernatremia in elderly patients who are expected to have increased prescriptions of tolvaptan.Correspondence to:
Takaya Uno, PhD
Department of Pharmacy
National Cerebral and Cardiovascular Center
564-8565, Suita, Osaka, Japan
Email: [email protected]
Original
Association between sodium-glucose cotransporter 2 inhibitors and pancreatic cancer in the Japanese working-age population
Yuki Tanaka, Satoshi Yokoyama, Chihiro Nakagawa, Takaya Uno, and Kouichi Hosomi
Price
42.00 $
Volume 61 (2023) p. 492 - 502
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 61 – No. 11/2023 (492-502)
Association between sodium-glucose cotransporter 2 inhibitors and pancreatic cancer in the Japanese working-age population
Yuki Tanaka, Satoshi Yokoyama, Chihiro Nakagawa, Takaya Uno, and Kouichi Hosomi
Division of Drug Informatics, School of Pharmacy, Kindai University, Higashiosaka City, Osaka, Japan
Objective: Pancreatic cancer-related mortality is increasing worldwide, and prevention methods and effective novel therapies are required. In pancreatic cancer, sodium-glucose cotransporters (SGLT) are involved in glucose uptake. This study aimed to clarify the association between SGLT2 inhibitors and pancreatic cancer development.
Materials and methods: A nested case-control study was conducted using the JMDC administrative claims database (January 2005 to June 2020). Patients newly diagnosed with type 2 diabetes mellitus (T2DM) were included, and cases were defined as patients who developed pancreatic cancer. Patients with outcomes were randomly matched to a maximum of 20 controls according to age (± 5 years), sex, and calendar date (month and year) of the first T2DM diagnosis through risk set sampling.
Results: Of the 181,107 T2DM patients, 363 cases and 7,043 controls were selected with 14 and 457 patients prescribed SGLT2 inhibitors, respectively. Cumulative administration of SGLT2 inhibitors for > 180 days was significantly inversely associated with the development of pancreatic cancer (adjusted odds ratio: 0.58, 95% confidence interval: 0.31 – 0.99).
Conclusion: SGLT2 inhibitors may reduce the risk of developing pancreatic cancer in T2DM patients. The number of patients over 65 years of age was small in this study due to the nature of the data source. Further studies with larger sample sizes including older patients are needed.Correspondence to:
Satoshi Yokoyama, PhD
Division of Drug Informatics, School of Pharmacy
Kindai University
3-4-1 Kowakae, Higashi-Osaka,
Osaka, 577-8502, Japan
Email: [email protected]
