Biomedical subjects

Ryuya Horiuchi

Publications and source records attributed to Ryuya Horiuchi.

23 records · Page 2Linked to original sources

PubMed2003

Effect of the single CYP2C9*3 allele on pharmacokinetics and pharmacodynamics of losartan in healthy Japanese subjects.

OBJECTIVE: Losartan is metabolized to the active carboxylic acid metabolite EXP3174 by CYP2C9. In this study, we determined the effects of the single CYP2C9*3 variant on the pharmacokinetics and pharmacodynamics of losartan. METHODS: Seven healthy Japanese subjects ( CYP2C9*1/*1, n=4 and CYP2C9*1/*3, n=3) were phenotyped with a single dose of losartan (25 mg). Blood and urine samples were collected and assayed for losartan and EXP3174. Blood pressure and pulse rate were also measured using a sphygmomanometer. RESULTS: The maximum plasma concentration of EXP3174 was significantly (P<0.05) lower in the CYP2C9*1/*3 (n=3) group than in the CYP2C9*1/*1 (n=4) group. Diastolic blood pressure in the CYP2C9*1/*1 group, but not that in the CYP2C9*1/*3 group except for at 6 h and 8 h, was reduced from 1.5 h to 12 h compared with the baseline level. Systolic blood pressure in the CYP2C9*1/*1 group, but not that in the CYP2C9*1/*3 group, was reduced from 1 h to 12 h compared with the baseline level. The metabolic ratio (MR) of EXP3174 concentration to the losartan concentration in plasma at 6 h post-dosing and the 4-h to 8-h urinary EXP3174/losartan MR were significantly lower in the CYP2C9*1/*3 group than in the CYP2C9*1/*1 group. The plasma 6-h MR and the 4-h to 8-h urinary MR were significantly (P<0.05) correlated with the plasma AUC ratio (AUC(EXP3174)/AUC(losartan)), with Spearman rank correlation coefficients of 0.75 and 0.89, respectively. CONCLUSION: The single CYP2C9*3 variant reduces the metabolism of losartan and its hypotensive effect. Plasma MR, as well as urine MR, may be useful for phenotyping assays of CYP2C9 activity.

Adult↗

PubMed2003

Fluvoxamine modulates pain sensation and affective processing of pain in human brain.

To better understand the antinociceptive effect of fluvoxamine, we measured regional cerebral blood flow during laser-evoked pain and hot sensations using H(2)15O positron emission tomography and also subjective pain and hot sensations before and after fluvoxamine or placebo administration for 7 days to 12 healthy volunteers. The subjectively rated pain score was significantly reduced by fluvoxamine administration. Painful stimuli activated multiple brain regions. After fluvoxamine administration the ipsilateral anterior cingulate cortex (ACC), contralateral insular cortex (IC), and contralateral secondary somatosensory cortex (SII) activations were reduced. The bilateral IC activation was also reduced in the placebo group. These results suggest that fluvoxamine specifically reduced activation of the ACC and SII, which are areas concerned with the affective and integrative components of pain.

Adult↗

PubMed2003

Content and classification of clinical trials at a university hospital in Japan.

"Standards on the Implementation of Clinical Trials on Drugs (New GCP)" is a Japanese government policy established in April 1998 with the aim of satisfying scientific and ethical requirements for industry-sponsored research, i.e., registration-directed clinical trials and clinical trials intended to support reexamination or reevaluation applications. Since then, efforts for more effective implementation of clinical trials have been promoted, including establishment of a system to invite more active participation of subjects in clinical trials and improvement of a network of medical institutions conducting clinical trials. These efforts should help to reactivate clinical trials in Japan, which reportedly have become stagnant. Although the New GCP addresses the quality of industry-sponsored clinical trials, investigators also construct study protocols without industry involvement. We reviewed clinical trials submitted by investigators at Gunma University Hospital to institutional review boards (IRBs) from June 1999 to February 2002. Ten clinical research coordinators contributed to the present survey. A total of 151 investigator-initiated clinical trials reviewed included a wide variety of content; and investigators from many institutions and organizations conducted trials. Most of the ethical guidelines for approving proposed trials represented the provisions of the Declaration of Helsinki. However, additional guidelines prepared by the Japanese Ministry of Health, Labour and Welfare were also helpful. Development of a support system for clinical trails requires the contribution of clinical research coordinators. Flexible management and careful attention to both the protocol and its execution by the investigators were also important for promoting clinical trials on the basis of meticulous patient care.

Clinical Trials as Topic↗

PubMed2002

Successful treatment of severe hyperammonemia using sodium phenylacetate powder prepared in hospital pharmacy.

In order to treat a hyperammonemic patient with adult-onset type-II citrullinemia (CTLN2), sodium phenylacetate powder was prepared from chemical reagent grade phenylacetic acid in Gunma University Hospital. After purification by recrystalization, phenylacetic acid was neutralized with sodium carbonate and dried at 70 degrees C under reduced pressure. A solution of the prepared powder produced a single peak of m/z=181.0 (M+Na+) in electrospray-ionization-MS spectrogram. The content of phenylacetate was 74% of theoretical value, suggesting the existence of water of crystallization. The content of phenylacetate remained constant for 5 months under dark conditions at room temperature. The prepared sodium phenylacetate powder was orally administered to a 16-year-old patient with CTLN2 at a dosage of 12 g/d. The serum ammonia concentration of the patient, who did not show adequate response to intravenous arginine or oral sodium benzoic acid decreased remarkably to less than 100 microg/dl. Sodium phenylacetate powder should be an essential drug for the treatment of hyperammonemia caused by an inborn error of the urea cycle.

Adolescent↗

PubMed2002

[Case report summary browsing system for education of pharmaceutical students through the Internet].

We have developed a patient case database at Gunma University Hospital. The transmission of the data contained in this database via the Internet is protected by SSH encryption technology. The database may also function as an education tool for medical and pharmaceutical students who can access this system through the Internet using a special browser system that we have also developed. In a survey questionnaire relating to our system conducted among graduate students, most responded positively to its usefulness as an opportunity for exposure to actual clinical practice. Because this system can introduce students to realistic and daily practices at hospitals, it might have a great impact on Japanese pharmaceutical education in universities or pharmaceutical colleges where early exposure to actual hospital practices is not appropriately included in the curriculum. In addition, our system will function to establish a mutual feedback system between hospitals and basic research institutions such as pharmaceutical universities.

Case-Control Studies↗