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1. Effective prevention of sorafenib-related vascular damage induced adverse events and maintenance of hepatic function by dried bonito broth and histidine

Author

Sakai N, Kamimura K, Shinagawa-Kobayashi Y, Nagoya T, Niwa Y, Ko M, Setsu T, Sakamaki A, Yokoo T, Abe S, Kamimura H, Sugitani S, Yanagi M, and Terai S

Subjects
sorafenib, histidine, dried bonito broth, vascular area dimension, albumin, hepatocellular carcinoma, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Norihiro Sakai,1,* Kenya Kamimura,1,* Yoko Shinagawa-Kobayashi,1 Takuro Nagoya,1 Yusuke Niwa,1 Masayoshi Ko,1 Toru Setsu,1 Akira Sakamaki,1 Takeshi Yokoo,1 Satoshi Abe,1 Hiroteru Kamimura,1 Soichi Sugitani,2 Masahiko Yanagi,3 Shuji Terai11Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan; 2Department of Gastroenterology, Murakami General Hospital, Murakami, Niigata, Japan; 3Department of Gastroenterology, Ojiya General Hospital, Ojiya, Niigata, Japan*These authors contributed equally to this workBackground: Sorafenib (SOR) is an anti-angiogenic chemotherapeutic that prolongs the survival rates of patients with hepatocellular carcinoma. However, SOR also damages normal vasculature and causes associated adverse events, including hand–foot syndrome and hypertension (HT). We previously reported in an animal study that vascular damage resulted in the narrowing of the normal vascular dimension area in medaka fish (Oryzias), and histidine (HIS), a major amino acid contained in dried bonito broth (DBB), prevented these changes. Therefore, in the study, we analyzed the effects of DBB and HIS on SOR-related vascular damages and associated adverse events in patients.Materials and methods: Three-dimensional (3D) vascular images of abdominal regions reconstituted from computed tomography were assessed to compare vascular diameter prior to and following SOR administration in groups receiving SOR monotherapy, DBB+SOR, and HIS+SOR. The clinical courses of hand–foot syndrome and HT and the toxicities of SOR in biochemical assays were monitored and compared between the groups. Correlations between hepatic function and SOR-related changes in the portal venous area dimension were also assessed.Results: SOR-related vascular damage revealed narrowing of the normal abdominal vasculature in the human body, which was monitored using 3D images. The damage was ameliorated by DBB and HIS, however, HIS had a more marked effect, particularly on the renal arteries and portal vein (PV). Maintenance of blood flow contributed to the maintenance of total cholesterol, prothrombin time, albumin (ALB), and renal functions. Changes in the 3D vascular area dimension of the PV and level of serum ALB were significantly correlated. The occurrences of the clinical symptoms of hand–foot syndrome and HT were lower in the DBB- and HIS-treated groups.Conclusion: Our results clearly demonstrate that DBB and HIS prevented SOR-related abdominal vascular damage and effectively maintained hepatic function, and prevented clinical symptoms and toxicity.Trial registration: This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000025937 and UMIN000026898).Keywords: sorafenib, histidine, dried bonito broth, vascular area dimension, albumin, hepatocellular carcinoma

Published
2019

2. Prognostic value of subcutaneous adipose tissue volume in hepatocellular carcinoma treated with transcatheter intra-arterial therapy

Author

Kobayashi T, Kawai H, Nakano O, Abe S, Kamimura H, Sakamaki A, Kamimura K, Tsuchiya A, Takamura M, Yamagiwa S, and Terai S

Subjects
hepatocellular carcinoma, subcutaneous adipose tissue, transcatheter arterial chemoembolization, transcatheter arterial infusion chemotherapy, prognosis, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Takamasa Kobayashi, Hirokazu Kawai, Oki Nakano, Satoshi Abe, Hiroteru Kamimura, Akira Sakamaki, Kenya Kamimura, Atsunori Tsuchiya, Masaaki Takamura, Satoshi Yamagiwa,† Shuji Terai Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan †Dr Satoshi Yamagiwa passed away on May 4, 2018 Background: Prognosis of patients with hepatocellular carcinoma (HCC) who undergo transcatheter intra-arterial therapies, including transcatheter arterial chemoembolization and transcatheter arterial infusion chemotherapy, is affected by many clinical factors including liver function and tumor progression. However, the effect of body composition such as skeletal muscle and visceral and subcutaneous adipose tissues (VAT and SAT, respectively) on the prognosis of these patients remains unclear. We investigated the prognostic value of body composition in HCC patients treated with transcatheter intra-arterial therapies. Patients and methods: This study retrospectively evaluated 100 HCC patients treated with transcatheter intra-arterial therapies between 2005 and 2015. Areas of skeletal muscle, VAT, and SAT were measured on computed tomography images at third lumbar vertebra level and normalized by the height squared to calculate the skeletal muscle index, VAT index, and SAT index (SATI). The visceral to subcutaneous adipose tissue area ratio was also calculated. Overall survival (OS) was compared between high- and low-index groups for each body composition. Furthermore, prognostic significance was assessed by univariate and multivariate analyses using Cox proportional hazards models. Results: Among the body composition indexes, only SATI could significantly differentiate OS (p=0.012). Multivariate analysis showed that SATI (low- vs. high-SATI: HR, 2.065; 95% CI, 1.187–3.593; p=0.010), serum albumin (

Published
2018

4. Comment on: Role of inelastic tunneling through the insulating barrier in scanning-tunneling-microscope experiments on cuprate superconductors

Author

Bishop, A. R., Conradson, S. D., Bussmann-Holder, A., Dolgov, O., Keller, H., Khasanov, R., Mueller, K. A., Kresin, V. Z., Kamimura, H., and Mihailovic, D.

Subjects
Condensed Matter - Superconductivity, Condensed Matter - Other Condensed Matter
Abstract

In a recent letter [1] Pilgram, Rice and Sigrist (PRS) propose to perform oxygen isotope dependent conductivity measurements along the c-axis of the cuprate superconductor BSSCO. In Raman isotope data for vibrations along the c-axis from 1988 [2], and in site selective susceptibility experiments determining Tc, no isotope effects were observed for oxygen ions in the insulating layer [3]. Based on these earlier not by PRS quoted experiments, we argue that the suggestion made in Ref. 1 is not worth to be undertaken, and if it is carried through, no effect will be seen. From the meanwhile 12 years old site selective data [3] the observed isotope effects stem to nearly 100% from oxygen ions in the CuO2-planes. These results evidence polaronic behavior in these planes [4]., Comment: 3 pages, 1 figure

Published
2006

5. Real and marginal isotope effects in cuprate superconductors

Author

Bishop, A. R., Bussmann-Holder, A., Dolgov, O. V., Furrer, A., Kamimura, H., Keller, H., Khasanov, R., Kremer, R. K., Manske, D., Mueller, K. A., and Simon, A.

Subjects
Condensed Matter - Superconductivity
Abstract

We critically review recent and earlier results on isotope effects in cuprate superconductors and emphasize that the sample preparation and the isotope exchange and back exchange are crucial in understanding and interpreting the data. Only extremely careful preparation techniques yield reliable results and permit differentiation between real isotope effects and marginal ones. The former are substantial and highlight the lattice vibrational importance in cuprate superconductors., Comment: 7 pages, 4 figures

Published
2006

29. Disorder induced interface states and their influence on the Al/Ge nanowires Schottky devices.

Author

Simon, R. A., Kamimura, H., Berengue, O. M., Leite, E. R., and Chiquito, A. J.

Subjects
*NANOWIRES, *SEMICONDUCTOR research, *SURFACES (Physics), *ALUMINUM, *GERMANIUM, *SCHOTTKY barrier diodes
Abstract

It has been demonstrated that the presence of oxide monolayers in semiconductor surfaces alters the electronic potential at surfaces and, consequently, can drastically affect the electronic transport features of a practical device such as a field effect transistor. In this work experimental and theoretical approaches to characterize Al/germanium nanowire Schottky devices by using samples covered with a thin oxide layer (2 nm width) were explored. It was also demonstrated that the oxide layer on Ge causes a weak dependence of the metal work function on Schottky barrier heights indicating the presence of Fermi level pinning. From theoretical calculations the pinning factor S was estimated to range between 0.52 and 0.89, indicating a weak Fermi level pinning which is induced by the presence of charge localization at all nanowires' surface coming from interface states. [ABSTRACT FROM AUTHOR]

Published
2013
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30. Characterization of the diffusion properties of different gadolinium-based MRI contrast agents after ultrasound induced blood–brain barrier permeabilization

Author

Fowlkes, B, Ghanouni, P, Sanghvi, N, Coussios, C, Lyon, Pc, Gray, M, Mannaris, C, Victor, Mds, Stride, E, Cleveland, R, Carlisle, R, Feng, W, Middleton, M, Gleeson, F, Aubry, J, Pauly, Kb, Moonen, C, Vortman, J, Sharabi, S, Daniels, D, Last, D, Guez, D, Levy, Y, Volovick, A, Grinfeld, J, Rachmilevich, I, Amar, T, Zibly, Z, Mardor, Y, Harnof, S, Plaksin, M, Weissler, Y, Shoham, S, Kimmel, E, Naor, O, Farah, N, Paeng, D, Zhiyuan, X, Snell, J, Quigg, Ah, Eames, M, Jin, C, Everstine, Ac, Sheehan, Jp, Lopes, Bs, Kassell, N, Looi, T, Khokhlova, V, Mougenot, C, Hynynen, K, Drake, J, Slayton, M, Amodei, Rc, Compton, K, Mcnelly, A, Latt, D, Kearney, J, Melodelima, D, Dupre, A, Chen, Y, Perol, D, Vincenot, J, Chapelon, J, Rivoire, M, Guo, W, Ren, G, Shen, G, Neidrauer, M, Zubkov, L, Weingarten, Ms, Margolis, Dj, Lewin, Pa, Mcdannold, N, Sutton, J, Vykhodtseva, N, Livingstone, M, Kobus, T, Zhang, Y, Schwartz, M, Huang, Y, Lipsman, N, Jain, J, Chapman, M, Sankar, T, Lozano, A, Yeung, R, Damianou, C, Papadopoulos, N, Brokman, O, Zadicario, E, Brenner, O, Castel, D, Shih-Ying, W, Grondin, J, Zheng, W, Heidmann, M, Karakatsani, Me, Sánchez, Cjs, Ferrera, V, Konofagou, Ee, Yiannakou, M, Cho, H, Lee, H, Han, M, Choi, J, Lee, T, Ahn, S, Chang, Y, Park, J, Ellens, N, Partanen, A, Farahani, K, Airan, R, Carpentier, A, Canney, M, Vignot, A, Lafon, C, Delattre, J, Idbaih, A, Odéen, H, Bolster, B, Jeong, Ek, Parker, Dl, Gaur, P, Feng, X, Fielden, S, Meyer, C, Werner, B, Grissom, W, Marx, M, Weber, H, Taviani, V, Hargreaves, B, Tanaka, J, Kikuchi, K, Ishijima, A, Azuma, T, Minamihata, K, Yamaguchi, S, Nagamune, T, Sakuma, I, Takagi, S, Santin, Md, Marsac, L, Maimbourg, G, Monfort, M, Larrat, B, François, C, Lehéricy, S, Tanter, M, Samiotaki, G, Wang, S, Acosta, C, Feinberg, Er, Kovacs, Zi, Tsang-Wei, T, Papadakis, Gz, Reid, Wc, Hammoud, Da, Frank, Ja, Kim, S, Jikaria, N, Bresler, M, Qureshi, F, Xia, J, Tsui, P, Liu, H, Plata, Jc, Sveinsson, B, Salgaonkar, Va, Adams, M, Diederich, C, Ozhinsky, E, Bucknor, Md, Rieke, V, Mikhail, A, Severance, L, Negussie, Ah, Wood, B, de Greef, M, Schubert, G, Ries, M, Poorman, Me, Dockery, M, Chaplin, V, Dudzinski, So, Spears, R, Caskey, C, Giorgio, T, Costa, Mm, Papaevangelou, E, Shah, A, Rivens, I, Box, C, Bamber, J, ter Haar, G, Burks, Sr, Nagle, M, Nguyen, B, Milo, B, Nhan M., L, Song, S, Zhou, K, Nabi, G, Huang, Z, Ben-Ezra, S, Rosen, S, Mihcin, S, Strehlow, J, Karakitsios, I, Nhan, L, Schwenke, M, Demedts, D, Prentice, P, Haase, S, Preusser, T, Melzer, A, Mestas, J, Chettab, K, Gomez, Gs, Dumontet, C, Werle, B, Marquet, F, Bour, P, Vaillant, F, Amraoui, S, Dubois, R, Ritter, P, Haïssaguerre, M, Hocini, M, Bernus, O, Quesson, B, Livneh, A, Adam, D, Robin, J, Arnal, B, Fink, M, Pernot, M, Khokhlova, Td, Schade, Gr, Wang, Y, Kreider, W, Simon, J, Starr, F, Karzova, M, Maxwell, A, Bailey, Mr, Lundt, Je, Allen, Sp, Sukovich, Jr, Hall, T, Zhen, X, May, P, Lin, Dw, Constans, C, Deffieux, T, Park, E, Ahn, Yd, Kang, Sy, Park, D, Lee, Jy, Vidal-Jove, J, Perich, E, Ruiz, A, Jaen, A, Eres, N, del Castillo, Ma, Myers, R, Kwan, J, Coviello, C, Rowe, C, Crake, C, Finn, S, Jackson, E, Pouliopoulos, A, Caiqin, L, Tinguely, M, Tang, M, Garbin, V, Choi, Jj, Folkes, L, Stratford, M, Nwokeoha, S, Tong, L, Farr, N, D’Andrea, S, Gravelle, K, Chen, H, Lee, D, Hwang, Jh, Tardoski, S, Ngo, J, Gineyts, E, Roux, J, Clézardin, P, Conti, A, Magnin, R, Gerstenmayer, M, Lux, F, Tillement, O, Mériaux, S, Penna, Sd, Romani, Gl, Dumont, E, Sun, T, Power, C, Miller, E, Sapozhnikov, O, Tsysar, S, Yuldashev, Pv, Svet, V, Dongli, L, Pellegrino, A, Petrinic, N, Siviour, C, Jerusalem, A, Cunitz, Bw, Dunmire, B, Inserra, C, Guedra, M, Mauger, C, Gilles, B, Solovchuk, M, Sheu, Twh, Thiriet, M, Zhou, Y, Neufeld, E, Baumgartner, C, Payne, D, Kyriakou, A, Kuster, N, Xiao, X, Mcleod, H, Dillon, C, Payne, A, Khokhova, Va, Sinilshchikov, I, Andriyakhina, Y, Rybyanets, A, Shvetsova, N, Berkovich, A, Shvetsov, I, Shaw, Cj, Civale, J, Giussani, D, Lees, C, Ozenne, V, Toupin, S, Salgaonkar, V, Kaye, E, Monette, S, Maybody, M, Srimathveeravalli, G, Solomon, S, Gulati, A, Bezzi, M, Jenne, Jw, Lango, T, Müller, M, Sat, G, Tanner, C, Zangos, S, Günther, M, Dinh, Ah, Niaf, E, Bratan, F, Guillen, N, Souchon, R, Lartizien, C, Crouzet, S, Rouviere, O, Han, Y, Payen, T, Palermo, C, Sastra, S, Olive, K, van Breugel, Jm, van den Bosch, Ma, Fellah, B, Le Bihan, D, Hernandez-Garcia, L, Cain, Ca, Lyka, E, Elbes, D, Chunhui, L, Tamano, S, Jimbo, H, Yoshizawa, S, Fujiwara, K, Itani, K, Umemura, S, Stoianovici, D, Zaini, Z, Takagi, R, Zong, S, Watkins, R, Pascal-Tenorio, A, Jones, P, Butts-Pauly, K, Bouley, D, Lin, C, Hsieh, H, Wei, K, Garnier, C, Renault, G, Seifabadi, R, Wilson, E, Eranki, A, Kim, P, Lübke, D, Huber, P, Georgii, J, Dresky, Cv, Haller, J, Yarmolenko, P, Sharma, K, Celik, H, Guofeng, L, Qiu, W, Zheng, H, Tsai, M, Chu, P, Webb, T, Vyas, U, Walker, M, Zhong, J, Waspe, Ac, Hodaie, M, Yang, F, Huang, S, Zur, Y, Assif, B, Aurup, C, Kamimura, H, Carneiro, Aa, Rothlübbers, S, Schwaab, J, Houston, G, Azhari, H, Weiss, N, Sosna, J, Goldberg, Sn, Barrere, V, Jang, Kw, Lewis, B, Wang, X, Suomi, V, Edwards, D, Larrabee, Z, Hananel, A, Rafaely, B, Debbiny, Re, Dekel, Cz, Assa, M, Menikou, G, Mouratidis, P, Pineda-Pardo, Ja, de Pedro, Mda, Martinez, R, Hernandez, F, Casas, S, Oliver, C, Pastor, P, Vela, L, Obeso, J, Greillier, P, Zorgani, A, Catheline, S, Solovov, V, Vozdvizhenskiy, Mo, Orlov, Ae, Chueh-Hung, W, Sun, M, Shih, Tt, Chen, W, Prieur, F, Pillon, A, Cartron, V, Cebe, P, Chansard, N, Lafond, M, Seya, Pm, Bera, J, Boissenot, T, Fattal, E, Bordat, A, Chacun, H, Guetin, C, Tsapis, N, Maruyama, K, Unga, J, Suzuki, R, Fant, C, Rogez, B, Afadzi, M, Myhre, Of, Vea, S, Bjørkøy, A, Yemane, Pt, van Wamel, A, Berg, S, Hansen, R, Angelsen, B, and Davies, C

Subjects
Settore FIS/07
Published
2017

31. Oxygen-induced metal-insulator-transition on single crystalline metal oxide wires.

Author

Berengue, O. M., Amorim, C. A., Kamimura, H., Chiquito, A. J., and Leite, E. R.

Subjects
METAL-insulator transitions, OXYGEN, SINGLE crystals, METALLIC oxides, WIRE, PHONON scattering, POLYCRYSTALS, INDIUM oxide
Abstract

In this work we report on the transition from metal to insulator conduction of individual single crystalline In2 O3 wires induced by different oxygen concentration during their growth. The transport measurements revealed that the metallic conduction was mainly governed by the acoustic phonon scattering and the insulating character was addressed by the variable range hopping mechanism, which in turn can be considered as a first evidence of the occurrence of an Anderson-like metal-insulator-transition (MIT). The experimental data provided the critical carrier density to be 8×1018 cm-3 corresponding to a critical impurities spacing of 2.5 nm, which was found to be in agreement with previous reported data on polycrystalline indium oxide samples and with our recent finding on In2 O3 semiconducting samples. The approach presented here can be used to grow other metal oxide systems in which oxygen vacancies play a fundamental role for the electron transport features. [ABSTRACT FROM AUTHOR]

Published
2012
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33. Impurity Bands

Author

Kamimura, H., Butcher, Paul N., editor, March, Norman H., editor, and Tosi, Mario P., editor

Published
1986
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39. Effects of the concomitant administration of tamsulosin (0.8 mg) on the pharmacokinetic and safety profile of intravenous digoxin (LanoxinR) in normal healthy subjects: a placebo-controlled evaluation

Author

Swarz H, Jerome J. Schentag, Kamimura H, Alan Forrest, Y. Miyazawa, Y. Ito, and L. Paul Starkey

Subjects
Pharmacology, Digoxin, business.industry, Placebo-controlled study, Placebo, Pharmacokinetics, Tamsulosin, Oral administration, Concomitant, Anesthesia, medicine, Pharmacology (medical), Adverse effect, business, medicine.drug
Abstract

A 20-day, nonrandomized, open-label, placebo-controlled study was performed to investigate whether concomitant administration of tamsulosin (0.8 mg) affects the pharmacokinetic and safety profile of intravenous digoxin (0.5 mg) in healthy subjects. Ten healthy subjects aged 21-39 years received a single oral dose of placebo on study days 1-8 and tamsulosin on days 9-18. Tamsulosin was initiated at 0.4 mg/day and the dose was increased to 0.8 mg/day from day 11. On days 2 and 15, subjects received a single intravenous dose of digoxin (0.5 mg). Safety monitoring was carried out throughout the study. Following digoxin administration, blood was drawn and urine collected over a 96-h period for pharmacokinetic determinations. Plasma tamsulosin concentrations were measured at regular intervals after dosing on day 15. The digoxin pharmacokinetic parameters with and without concomitant tamsulosin were compared. No significant difference was observed, and no irregularity was found in the plasma tamsulosin concentration data. Six subjects experienced adverse events while receiving placebo and seven while on tamsulosin. The most frequent adverse event was mild dizziness reported by four subjects. Moderate chest pain was reported in two subjects, but this was not considered to be related to the administration of the study medications. Some significant changes in vital signs were observed; however, none was accompanied by symptoms of medical concern. These changes were not temporally related to the administration of study drugs. Thus, concurrent administration of digoxin with tamsulosin did not produce any change in the pharmacokinetics of digoxin and the safety profile was acceptable. As reflected in the prescribing information for tamsulosin, no adjustment in tamsulosin dosing is required when it is administered concomitantly with digoxin.

Published
2002

40. Effects of the Concomitant Administration of Tamsulosin (0.8 mg/Day) on the Pharmacokinetic and Safety Profile of Theophylline (5 mg/kg): A Placebo-Controlled Evaluation

Author

Alan Forrest, LP Starkey, Y. Ito, Kamimura H, Y. Miyazawa, Swarz H, and Jerome J. Schentag

Subjects
Male, Tamsulosin, Prostatic Hyperplasia, Administration, Oral, 030204 cardiovascular system & hematology, Pharmacology, Placebo, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Theophylline, Pharmacokinetics, Humans, Medicine, Drug Interactions, Adrenergic alpha-Antagonists, Sulfonamides, business.industry, Biochemistry (medical), Cell Biology, General Medicine, Middle Aged, Bronchodilator Agents, Safety profile, 030220 oncology & carcinogenesis, Concomitant, Anesthesia, Injections, Intravenous, Safety, business, Pharmacokinetic interaction, medicine.drug
Abstract

We performed a single-blind, sequential-design study to investigate the effects of concomitant oral tamsulosin 0.8 mg/day on the pharmacokinetics and safety of intravenous theophylline 5 mg/kg in healthy subjects. Ten healthy volunteers aged 19–39 years received placebo on study days 0, 1, 2 and 10 and tamsulosin on days 3–9. Theophylline was administered intravenously on days 1 and 9. Theophylline and tamsulosin pharmacokinetic data were determined following administration of the drugs on days 1 and 9 and day 9, respectively. No differences were observed in theophylline pharmacokinetic parameters with and without concomitant tamsulosin, and there were no abnormalites in tamsulosin pharmacokinetic data. Some significant changes in vital signs and a number of mild adverse reactions were reported, but the overall safety profile of tamsulosin and theophylline was acceptable. The results of the study suggest that no dose adjustment in tamsulosin is necessary when it is administered concomitantly with theophylline.

Published
2002

41. Effect of concomitant administration of cimetidine hydrochloride on the pharmacokinetic and safety profile of tamsulosin hydrochloride 0.4 mg in healthy subjects

Author

Yutaka Ito, Jerome J. Schentag, Alan Forrest, Kamimura H, Herbert Swarz, and Yasushi Miyazawa

Subjects
Pharmacology, business.industry, Antagonist, Context (language use), Drug interaction, Placebo, Pharmacokinetics, Tamsulosin, Oral administration, Medicine, Pharmacology (medical), Cimetidine, business, medicine.drug
Abstract

Background: Tamsulosin is an α 1 -adrenergic receptor antagonist that is metabolized primarily via the cytochrome P450 (CYP450) enzymes. Cimetidine hydrochloride is a histamine H 2 -receptor antagonist that is known to inhibit the activity of CYP enzymes. Objective: The purpose of this nonrandomized, sequential, drug-drug interaction study was to determine whether concomitant administration of cimetidine affects the pharmacokinetic and safety profile of tamsulosin 0.4 mg in healthy subjects. Methods: In this 11-day study, 10 healthy subjects aged 21 to 38 years received a single daily dose of placebo except on study days 2 and 8, when they received tamsulosin 0.4 mg. From day 5 through day 10, subjects also received a single oral tablet of cimetidine 400 mg every 6 hours. Safety monitoring was performed throughout the study. Plasma tamsulosin concentrations were determined at regular intervals after administration of the drug on days 2 and 8, and tamsulosin pharmacokinetic parameters were tested for equivalence on these 2 days. Results: Oral clearance of tamsulosin was significantly reduced ( P 0−∞ ) significantly increased ( P 0−∞ was not expected to be clinically important since tamsulosin is well tolerated at twice the dose used in this study. Some significant changes in vital signs (ie, diastolic blood pressure Conclusions: The results of this pharmacokinetic study were likely due to inhibition by cimetidine of CYP450 isozymes that catalyze tamsulosin metabolism. Although this study was conducted in young, healthy volunteers, thereby limiting the conclusions that can be drawn, the results, taken in the context of similar studies conducted in the target population, do not suggest that dose adjustment of tamsulosin is necessary in patients concurrently receiving cimetidine therapy.

Published
2002

42. Pharmacokinetics and safety of tamsulosin in subjects with normal and impaired renal or hepatic function

Author

Yasushi Miyazawa, Yutaka Ito, Jerome J. Schentag, Hiroshi Matsushima, Kamimura H, Herbert Swarz, and Robert A. Blum

Subjects
Pharmacology, medicine.medical_specialty, business.industry, Alpha (ethology), Renal function, Hyperplasia, medicine.disease, Endocrinology, Pharmacokinetics, Tamsulosin, Oral administration, Internal medicine, Toxicity, medicine, Pharmacology (medical), business, Kidney disease, medicine.drug
Abstract

Background: Tamsulosin is a potent alpha 1 -adrenergic receptor antagonist used in the treatment of benign prostatic hyperplasia. Objective: The purpose of these studies was to assess the pharmacokinetics and safety of tamsulosin in subjects with normal and impaired renal or hepatic function. Methods: In the first study, the pharmacokinetic profile of tamsulosin was compared in 12 subjects with renal function impairment and 6 with normal renal function. The second study was carried out in 8 subjects with hepatic insufficiency and 8 with normal hepatic function. Plasma and urine data were analyzed, and the effects of clinical and biochemical variables on pharmacokinetic parameters were evaluated. Results: Subjects with renal impairment had higher levels of alpha 1 -acid glycoprotein (α 1 -AGP) than those with normal renal function, and those with impaired liver function had lower levels than subjects with normal liver function. Since tamsulosin is highly bound to α 1 -AGP in vivo, these variations affected the levels of unbound fraction (f u ) of the drug. In renally impaired subjects f u was reduced in comparison with normal subjects, and was significantly increased in those with impaired hepatic function. These results correlated significantly with the total apparent clearance of the drug, whereas parameters indicative of renal or hepatic function did not. Conclusions: The results of the 2 studies indicate that the pharmacokinetics and safety profile of tamsulosin are not significantly influenced by renal or hepatic function. This suggests that no dose adjustment of tamsulosin is necessary in patients with renal or hepatic insufficiency.

Published
2001

43. Plastic homology of bcc metals

Author

T. SUZUKI, Y. KAMIMURA, H. O. K. KIRCH

Subjects
Physics and Astronomy (miscellaneous), Metals and Alloys, General Materials Science, Condensed Matter Physics, Electronic, Optical and Magnetic Materials
Published
1999

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