Masaharu Takeyama
Oita University
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Featured researches published by Masaharu Takeyama.
Chemotherapy | 2012
Yosuke Suzuki; Kanako Kawasaki; Yuhki Sato; Issei Tokimatsu; Hiroki Itoh; Kazufumi Hiramatsu; Masaharu Takeyama; Jun-ichi Kadota
Background: We analyzed the pharmacokinetic-pharmacodynamic relationship of vancomycin to determine the drug exposure parameters that correlate with the efficacy and nephrotoxicity of vancomycin in patients with methicillin-resistant Staphylococcus aureus pneumonia and evaluated the need to use peak concentration in therapeutic drug monitoring (TDM). Methods: Serum drug concentrations of 31 hospitalized patients treated with vancomycin for methicillin-resistant S. aureus pneumonia were collected. Results: Significant differences in trough concentration (Cmin)/minimum inhibitory concentration (MIC) and area under the serum concentration-time curve (AUC0–24)/MIC were observed between the response and non-response groups. Significant differences in Cmin and AUC0–24 were observed between the nephrotoxicity and non-nephrotoxicity groups. Receiver operating characteristic curves revealed high predictive values of Cmin/MIC and AUC0–24/MIC for efficacy and of Cmin and AUC0–24 for safety of vancomycin. Conclusions: These results suggest little need to use peak concentration in vancomycin TDM because Cmin/MIC and Cmin are sufficient to predict the efficacy and safety of vancomycin.
Annals of Otology, Rhinology, and Laryngology | 1993
Tokuo Chaen; Noritake Watanabe; Kazuo Mori; Goro Mogi; Masaharu Takeyama
To clarify the role of substance P (SP) and vasoactive intestinal peptide (VIP) in nasal allergy, we measured their concentrations in the nasal secretions and plasma of normal subjects and patients with nasal allergy to house dust and Japanese cedar pollen by competitive enzyme-linked immunoassay. The mean levels of SP (224 pmol/L) and VIP (41.6 pmol/L) in the nasal secretions of normal subjects were significantly higher than those in plasma (SP 3.04 pmol/L and VIP 1.04 pmol/L; p < .01). The mean levels of SP and VIP in the nasal secretions of the pollinosis group were significantly higher than those of the control group (p < .05 and p < .01), while the levels of the house dust allergy group were not higher than those of the control group. Intranasal allergen challenge significantly reduced SP levels in the nasal secretions of the allergy groups, while it did not influence VIP levels in the nasal secretions. These findings suggest that SP and VIP are actively secreted into the nose and may play an important role in the allergic reaction on the surface of the human nasal mucosa.
American Journal of Rhinology | 1997
Mitsunori Shinoda; Noritake Watanabe; Takeshi Suko; Goro Mogi; Masaharu Takeyama
To clarify the effects of anti-allergic drugs on substance P (SP) and vasoactive intestinal peptide (VIP) levels in nasal secretions, we employed competitive enzyme-linked immunoassays to measure concentrations of those neuropeptides in nasal secretions from 40 patients with house dust nasal allergy before and after administration of azelastine and oxatomide. One mg of azelastine and 30 mg of oxatomide were administrated twice a day for 4 weeks. Mean values of SP concentrations and ratios of SP to total protein of the nasal allergy group were significantly higher than those of the control group (p < 0.002). The VIP/total protein ratio of the allergy group was also significantly higher than that of the control group, although the VIP concentration alone was not. Mean levels of SP and VIP from patients with severe symptoms were significantly higher than those of the control group (p < 0.05), although those values were not significantly different between patients with moderate symptoms and control subjects. Azelastine and oxatomide effectively reduced SP levels in nasal secretions (p < 0.005), but they did not significantly decrease VIP levels. The reduction of SP levels was significant in patients with excellent responses to those drugs (p < 0.005), but not in patients with poor responses. These findings suggest that SP and VIP levels in nasal secretions may reflect the clinical state of nasal allergy and be one of the better parameters available for evaluating the clinical efficacy of anti-allergic drugs against nasal allergy.
Pharmacology | 2006
Fumihiko Katagiri; Toru Shiga; Shin Inoue; Yuhki Sato; Hiroki Itoh; Masaharu Takeyama
Itopride hydrochloride (itopride), a gastrokinetic drug, has recently been evaluated for its clinical usefulness in functional dyspepsia. We investigated effects of itopride on human plasma gastrin-, somatostatin-, motilin-, and cholecystokinin (CCK)-like immunoreactive substances (IS); adrenocorticotropic hormone (ACTH)-immunoreactive substances (IS), and cortisol under stress conditions in healthy subjects. A single administration of itopride caused significant increases in plasma somatostatin- and motilin-IS levels compared to placebo. Itopride significantly decreased plasma CCK-IS, and suppressed the ACTH-IS level compared to placebo. We hypothesize that itopride may have an accelerating gastric emptying effect, and a modulatory effect on the hypothalamo-pituitary-adrenal axis and autonomic nervous functions. These effects might be beneficial in stress-related diseases, suggesting that itopride has clinicopharmacological activities.
Journal of Pharmacy and Pharmacology | 2001
Toshiaki Nagano; Masaharu Takeyama
Anethole trithione, a choleretic, has been reported to be effective in the treatment of dry mouth. We have examined the effects of chronic treatment with anethole trithione on salivary secretion, substance P immunoreactive substance (SP‐IS) and α‐calcitonin gene‐related peptide immunoreactive substance (α‐CGRP‐IS) concentrations in human saliva. Anethole trithione caused significant increases of saliva SP‐IS concentrations from the day 13 (25.3 ± 1.6 pg mL−1) to day 14 (25.8 ± 1.7 pg mL−1) compared with day 1 (19.9 ± 1.9 pg mL−1). Anethole trithione caused significant increase in saliva α‐CGRP‐IS concentration on day 14 (39.9 ± 4.7 pg mL−1) compared with day 1 (27.7 ± 4.7 pg mL−1). Anethole trithione significantly increased the sialosis volumes from day 11 to day 14 (1.6 ± 0.1–1.7 ± 0.2 mL) compared with the day 1 (1.2 ± 0.2 mL). Simple linear regression of the increase in sialosis volume with saliva SP‐IS (r = 0.94) and α‐CGRP‐IS (r = 0.97) concentrations was found. These results demonstrated that chronic treatment with anethole trithione affected saliva SP‐IS and α‐CGRP‐IS concentration in human saliva and sialosis volume.
Therapeutic Drug Monitoring | 1992
Yasuo Kodama; Yuichi Koike; Hiroo Kimoto; Fumitaka Yasunaga; Masaharu Takeyama; Iwao Teraoka; Isao Fujii
Two hundred milligrams of valproic acid (VPA) was administered orally to seven healthy adults at 9:00 and 21:00 h for 5 consecutive days, including the morning dose on day 6. On the sixth day, blood samples were drawn at 0, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 3, and 6 h after the morning dose. Binding of VPA to serum protein was evaluated by ultrafiltration, and total and unbound VPA concentrations were determined by fluorescence polarization immunoassay. Binding parameters of VPA to serum protein were calculated for each subject by the Scatchard analysis. The binding parameters obtained from seven subjects showed that the mean association constant (K) was 2.72 x 104 L/mol while the total number of binding sites (nPt) was 789 μmol/L. There were marked interindividual variations and the coefficient of variation was 42% for K and 28% for nPt. These results show that endogenous free fatty acids (FFAs) significantly reduce the binding affinity of VPA to serum albumin (p < 0.05). In addition, they suggest the possibility that the primary binding sites for VPA can be strongly reduced by FFAs. Therefore, we consider that interindividual differences in binding parameters may be clinically important.
International Journal of Peptide and Protein Research | 2009
Haruaki Yajima; Masaharu Takeyama; Kaname Koyama; Takayoshi Tobe; Kazutomo Inoue; Tamotsu Kawano; Hideki Adachi
The octacosapeptide amide corresponding to the entire amino acid sequence of chicken VIP was synthesized in a conventional manner, using a new arginine derivative, NG-mesitylene-2-sulfonylarginine, Arg(Mts). Treatment of a fragment, Z(OMe)-Thr-Asp-Asn-Tyr-NHNH2 with methanesulfonic acid or HBr was found to give a product with a low recovery of Asp, after aminopeptidase digestion. Ring closure of the Asp-Asn unit seemed to be responsible for this phenomenon. Deprotection with HF or TFA exhibited definitely less such a tendency. In the final step of the synthesis, all protecting groups, including the Mts group, were removed by HF in the presence of m-cresol and the deprotected peptide was purified by ion-exchange chromatography on CM-cellulose followed by isoelectric focusing in Ampholine pH 9--1. Synthetic peptide exhibited the identical Rf value with that of natural chicken VIP and was active as the natural peptide.
Journal of Pharmacy and Pharmacology | 2001
Hiroki Itoh; Toshiaki Nagano; Masaharu Takeyama
The effect of cisapride on plasma concentrations of paracetamol was investigated with respect to hepatic metabolism. Paracetamol (1 g) together with cisapride (7.5 mg) or placebo was orally administered to five healthy male volunteers. Venous blood samples were taken before and after administration. Plasma paracetamol and its glucuronide and sulfate conjugates were measured by HPLC. The pharmacokinetic variables were calculated from the plasma concentration‐time curves of each volunteer. The area under the plasma paracetamol concentration‐time curve from 0 to 180 min (mean ± s.d.) increased from 1875.0 ± 112.8 μg min mL−1 (placebo coadministration) to 2238.8 ± 125.8 μg min mL−1 (cisapride coadministration) (P < 0.01). The mean maximum plasma paracetamol concentration (18.2 μg mL−1) with placebo was reached 30 min after administration, whereas mean maximum plasma paracetamol concentration (21.2 μg mL−1) with cisapride occurred 45 min after administration. The plasma paracetamol concentrations with cisapride were significantly greater at 45 to 120 min after administration compared with placebo. Plasma paracetamol glucuronide conjugate concentrations with cisapride were decreased at 15 to 60 min compared with placebo (P < 0.05), whereas plasma paracetamol sulfate conjugate concentrations did not change significantly. Hence the coadministration of paracetamol with cisapride reduced plasma paracetamol glucuronide concentrations and increased plasma paracetamol concentrations, presumably due to inhibition of paracetamol metabolism via paracetamol glucuronyltransferase. Thus, care is necessary when paracetamol and cisapride are coadministered.
Biochemical and Biophysical Research Communications | 1991
Masaharu Takeyama; Kazuhiro Kondo; Fusako Takayama; Rie Kondo; Hiroyuki Murata; Isao Miyakawa
The level of a gastrin releasing peptide-like immunoreactive substance (GRP-IS) in human milk and plasma during late pregnancy and after delivery was measured. GRP-IS in milk increased during late pregnancy (1.3 nM at 39 weeks) and decreased after delivery (100 pM). GRP-IS in plasma during late pregnancy and after delivery was much lower (below 2 pM). By using HPLC and gel-filtration chromatography, two peaks of GRP-IS were purified. The one was coeluted with GRP (18-27) and the other was a prohormone. The GRP-IS in milk during pregnancy was mostly composed of proGRP. These results suggest that GRP may be produced and secreted in mammary glands.
Journal of Pharmacy and Pharmacology | 2011
Yosuke Suzuki; Hiroki Itoh; Tomohide Abe; Fumihiro Nishimura; Yuhki Sato; Masaharu Takeyama
Objectives The aim of this study was to establish the population protein binding parameters of valproic acid (VPA) in patients with epilepsy receiving VPA monotherapy and those receiving VPA combined with other antiepileptic drugs.