Keisou Masuhara
St. Marianna University School of Medicine
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Cancer Chemotherapy and Pharmacology | 1996
Naomi Nagai; Masafumi Kinoshita; Hiroyasu Ogata; Daijiro Tsujino; Yuji Wada; Kazuhiko Someya; Tetsuro Ohno; Keisou Masuhara; Yoshio Tanaka; Katsuhiko Kato; Haruki Nagai; Akira Yokoyama; Yuzou Kurita
Abstract Purpose: The relationships between pharmacokinetic parameters of unchanged cisplatin (CDDP) and several markers for nephrotoxicity after CDDP infusion (80 mg/m2) over 2 and 4 h were quantitated in patients with various cancers (lung, stomach and colon cancers and mediastinal tumor). Methods: Plasma and urinary levels of unchanged CDDP were measured using a specific high-performance liquid chromatography method. Pharmacokinetic parameters were calculated according to the model-independent method. The nephrotoxicity markers, blood urea nitrogen (BUN), serum creatinine (SCr), plasma and urinary β2-microglobulin (BMGp and BMGu), urinary N-acetyl-β-D-glucosaminidase (NAG) and creatinine clearance (CCR) were monitored for 30 days following CDDP administration. Results: The maximum plasma concentration (Cmax), maximum urinary excretion rate (dAe/dtmax), area under the plasma concentration-time curve from time zero to infinity (AUC), cumulative amount excreted in urine from time zero to infinity (Ae), total clearance (Clt), renal clearance (Clr) and plasma half-life (t1/2) of unchanged CDDP were not significantly different between the 2-h and 4-h infusion schedules. The values of the nephrotoxicity markers changed significantly following CDDP administration, suggesting that CDDP chemotherapy (80 mg/m2) caused nephrotoxicity. The Cmax of unchanged CDDP was the most informative pharmacokinetic parameter for nephrotoxicity. Cmax was related to maximum BUN, maximum SCr and minimum CCR levels in 27 CDDP treatments according to an exponential model. Conclusion: In order to attain more effective CDDP chemotherapy with minimum nephrotoxicity, the present pharmacokinetic and pharmacodynamic studies suggest that the Cmax or steady-state plasma level of unchanged CDDP should be maintained between 1.5 and 2 μg/ml in a standard continuous infusion schedule over 2 h and 4 h.
The Journal of Clinical Pharmacology | 1998
Naomi Nagai; Hiroyasu Ogata; Yuji Wada; Daijiro Tsujino; Kazuhiko Someya; Tetsuro Ohno; Keisou Masuhara; Yoshio Tanaka; Haruki Takahashi; Haruki Nagai; Katsuhiko Kato; Yoichi Koshiba; Tamotsu Igarashi; Akira Yokoyama; Koichi Kinameri; Toshiyuki Kato; Yuzou Kurita
The population pharmacokinetics and pharmacodynamics of cisplatin (CDDP) were evaluated based on a mixed‐effect model using the NONMEM program. Unchanged CDDP in plasma was measured as a biologically active platinum species during CDDP chemotherapy, using high‐performance liquid chromatography. Plasma concentration measurements (157) of unchanged CDDP from 26 patients with cancer receiving 80 mg/m2 CDDP by infusion over 2 hours, 3.5 hours, or 4 hours were analyzed according to a one‐compartment model. The influences of individual characteristics such as body weight, dose schedule, course, and clinical laboratory values (renal function markers, albumin) on total body clearance (Cl) and volume of distribution (Vd) were examined. In the final pharmacokinetic model, body surface area and dose schedule affected Cl of unchanged CDDP. The Cl of CDDP was increased by 27.3% after the 2‐hour infusion schedule compared with Cl after the longer infusions. The Vd was estimated as 13.4 L/m2. The interindividual variability for Cl and Vd and residual variability were 22.9%, 30.9%, and 35.5%, respectively. The relationships between maximum concentration (Cmax) of unchanged CDDP and maximum blood urea nitrogen (BUNmax), or minimum creatinine clearance (ClCr,min) over a 1‐month period after CDDP administration were evaluated according to linear, exponential, or maximum response (Emax) models. The linear or Emax model described pharmacodynamics most successfully, with relatively large interindividual variability for both slope and EC50 (more than 25%). Residual variability was 15.3% and 17.1% in BUNmax and ClCrmin, respectively. The population means and interindividual and residual variability of pharmacokinetics and pharmacodynamics of CDDP were evaluated using the NONMEM program. The results of this study show that the population pharmacokinetic and pharmacodynamic approach could be useful to manage CDDP nephrotoxicity using sparse data in a clinical setting.
Pharmacotherapy | 2005
Tetsuro Kusaba; Yusuke Konno; Shigeo Hatta; Tomoya Fujino; Takashi Yasuda; Hiroshi Miura; Hiroyo Sasaki; Jun Okabayashi; Mei Murao; Tsutomu Sakurada; Goro Imai; Sayuri Shirai; Shingo Kuboshima; Yoshinori Shima; Goichi Ogimoto; Takeo Sato; Keisou Masuhara; Kenjiro Kimura
Study Objective. To compare the absorption profile of cyclosporine after preprandial administration with that after postprandial administration, and to determine which administration time resulted in a more stable absorption profile and the timing of the drug concentration that was the most reliable marker for monitoring drug absorption.
The Journal of Clinical Pharmacology | 2006
Ryuichi Ogawa; Ryoji Kishi; Kiyoshi Mihara; Harumi Takahashi; Akihiko Takagi; Naoki Matsumoto; Keisou Masuhara; Kiyoshi Nakazawa; Fumihiko Miyake; Shinichi Kobayashi; Hirotoshi Echizen
Population pharmacokinetics (PK) of a sodium channel—blocking antiarrhythmic, pilsicainide, was studied using the nonlinear mixed‐effects modeling technique in 91 patients with cardiac arrhythmias (80 suspected Brugada syndrome [BrS] and 11 with atrial fibrillation) who received an intravenous infusion of 10 mg of the drug. Population pharmacodynamic (PD) analysis was also performed using an effect compartment model. PD responses were assessed by changes in electrocardiogram (ECG) pattern (BrS‐like elevation of ST‐segment) and conduction parameters. The final PK model showed that gender (values were 50% lower in women than in men) and creatinine clearance were significant (P < .01) covariates of weight‐normalized systemic clearance of pilsicainide. Patients who showed a BrS‐like ECG pattern after the drug administration also showed a significantly (P < .01) greater prolongation in His‐Purkinje conduction compared to the remaining patients. In conclusion, female gender, renal dysfunction, and the drug‐induced BrS‐like ECG morphology may be associated with augmented ECG responses to pilsicainide.
Journal of Chromatography B: Biomedical Sciences and Applications | 1990
Masafumi Kinoshita; Naomi Yoshimura; Hiroyasu Ogata; Daijiro Tsujino; Toshiaki Takahashi; Satoru Takahashi; Yuji Wada; Kazuhiko Someya; Tetsuro Ohno; Keisou Masuhara; Yoshio Tanaka
Clinical and Experimental Nephrology | 2009
Sayuri Shirai; Takashi Yasuda; Hiroki Tsuchida; Shingo Kuboshima; Yusuke Konno; Yoshinori Shima; Takeo Sato; Shigeo Hatta; Keisou Masuhara; Kenjirou Kimura
Yakugaku Zasshi-journal of The Pharmaceutical Society of Japan | 2005
Kenichi Nakazono; Yoshiyuki Watanabe; Shinichi Nakaya; Yoshie Asami; Keisou Masuhara; Fumio Itoh; Hiroyasu Ogata
日本臨床生理学会雑誌 = Japanese journal of applied physiology | 2008
Masatoshi Hara; Yuko Tohyo; Hidehiko Atsuta; Fumihiko Miyake; Nobuyoshi Narita; Keito Torikai; Takahide Matsuda; Yumiko Shimozato; Ikkou Sakaue; Keisou Masuhara; Satoshi Imamura
Japanese Circulation Journal-english Edition | 2003
Ryuichi Ogawa; Kiyoshi Nakazawa; Ryoji Kishi; Akihiko Takagi; Naoki Matsumoto; Keisou Masuhara; Fumihiko Miyake; Shinichi Kobayashi; Hirotoshi Echizen
Japanese Circulation Journal-english Edition | 2003
Ryuichi Ogawa; Kiyoshi Nakazawa; Ryoji Kishi; Akihiko Takagi; Naoki Matsumoto; Keisou Masuhara; Fumihiko Miyake; Shinichi Kobayashi; Hirotoshi Echizen