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排序方式: 共有146条查询结果,搜索用时 46 毫秒
21.
Furuishi T Oda S Saito H Fukami T Suzuki T Tomono K 《Biological & pharmaceutical bulletin》2007,30(7):1350-1353
The effect of permeation enhancers on the percutaneous absorption of pentazocine (PTZ) was investigated in excised hairless mice using Franz diffusion cells in vitro. The enhancing effect on the percutaneous absorption of PTZ from the isopropyl myristate (IPM) solution system was improved with glyceryl monocaprylate (GEFA-C(8)), which is a kind of glycerol ester of fatty acid (GEFA). The flux of PTZ through the skin was ca. 4 times higher compared with IPM alone, while a less enhancing effect of glyceryl dicaprylate (GEFA-DiC(8)) and glyceryl tricaprylate (GEFA-TriC(8)) on the skin permeation of PTZ was found. Moreover, maximum enhancement of PTZ flux was observed with glyceryl monocaproate (GEFA-C(6)) among various alkyl chains (C(2)-C(18)) of monoglycerides. These results indicated that the IPM solution system combination with GEFA may be used to develop a transdermal formulation with improved skin permeation of PTZ. 相似文献
22.
Toyofumi Suzuki Mariko Miyata Chika Zaima Takayuki Furuishi Toshiro Fukami Fumihiko Kugawa Kazuo Tomono 《Journal of pharmaceutical sciences》2010,99(1):413-421
The blood–brain barrier (BBB) transport of naloxone, a potent and specific opioid antagonist, was investigated in rats using the brain uptake index method and the brain efflux index method. The apparent influx clearance of [3H]naloxone across the BBB was 0.305 mL/min/g brain. [3H]naloxone was eliminated from the brain with an apparent elimination half-life of 15.1 min after microinjection into the parietal cortex area 2 regions of the rat brain. The apparent efflux clearance of [3H]naloxone across the BBB was 0.152 mL/min/g brain, which was calculated from the elimination rate constant (4.79 × 10?2 min?1) and the distribution volume in the brain (3.18 mL/g brain). The influx clearance across the BBB was two times greater than the efflux clearance. The elimination of [3H]naloxone from the brain was not inhibited in the presence of the typical P-glycoprotein (P-gp) inhibitors such as quinidine, verapamil, vinblastine, and vincristine, indicating that naloxone is not a P-gp substrate in the rat. In vitro experiments by using human multidrug resistance 1 (MDR1)/P-gp overexpressing HeLa cells showed that the uptake of naloxone by the cells did not change in the presence of the P-gp inhibitors. In conclusion, the present results obtained from in vivo and in vitro studies suggest that P-gp is not involved in the BBB transport of naloxone. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:413–421, 2010 相似文献
23.
Toyofumi Suzuki Aya Ohmuro Mariko Miyata Takayuki Furuishi Shinji Hidaka Fumihiko Kugawa Toshiro Fukami Kazuo Tomono 《Biopharmaceutics & drug disposition》2010,31(4):243-252
Naloxone, a potent and specific opioid antagonist, has been shown in previous studies to have an influx clearance across the rat blood–brain barrier (BBB) two times greater than the efflux clearance. The purpose of the present study was to characterize the influx transport of naloxone across the rat BBB using the brain uptake index (BUI) method. The initial uptake rate of [3H]naloxone exhibited saturability in a concentration‐dependent manner (concentration range 0.5 µM to 15 mM ) in the presence of unlabeled naloxone. These results indicate that both passive diffusion and a carrier‐mediated transport mechanism are operating. The in vivo kinetic parameters were estimated as follows: the Michaelis constant, Kt, was 2.99±0.71 mM ; the maximum uptake rate, Jmax, was 0.477±0.083 µmol/min/g brain; and the nonsaturable first‐order rate constant, Kd, was 0.160±0.044 ml/min/g brain. The uptake of [3H]naloxone by the rat brain increased as the pH of the injected solution was increased from 5.5 to 8.5 and was strongly inhibited by cationic H1‐antagonists such as pyrilamine and diphenhydramine and cationic drugs such as lidocaine and propranolol. In contrast, the BBB transport of [3H]naloxone was not affected by any typical substrates for organic cation transport systems such as tetraethylammonium, ergothioneine or L ‐carnitine or substrates for organic anion transport systems such as p‐aminohippuric acid, benzylpenicillin or pravastatin. The present results suggest that a pH‐dependent and saturable influx transport system that is a selective transporter for cationic H1‐antagonists is involved in the BBB transport of naloxone in the rat. Copyright © 2010 John Wiley & Sons, Ltd. 相似文献
24.
Toyofumi Suzuki Chika Zaima Yoshiaki Moriki Toshiro Fukami Kazuo Tomono 《Journal of drug targeting》2013,21(1):67-74
The involvement of P-glycoprotein (P-gp) in buprenorphine (BNP) transport at the blood–brain barrier (BBB) in rats was investigated in vivo by means of both the brain uptake index technique and the brain efflux index technique. P-gp inhibitors, such as cyclosporin A, quinidine and verapamil, enhanced the apparent brain uptake of [3H]BNP by 1.5-fold. The increment of the BNP uptake by the brain suggests the involvement of a P-gp efflux mechanism of BNP transport at the BBB. [3H]BNP was eliminated with an apparent elimination half-life of 27.5 min after microinjection into the parietal cortex area 2 regions of the rat brain. The apparent efflux clearance of [3H]BNP across the BBB was 0.154 ml/min/g brain, which was calculated from the elimination rate constant (2.52 × 10? 2 min? 1) and the distribution volume in the brain (6.11 ml/g brain). The efflux transport of [3H]BNP was inhibited by range from 32 to 64% in the presence of P-gp inhibitors. The present results suggest that BNP is transported from the brain across the BBB via a P-gp-mediated efflux transport system, at least in part. 相似文献
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28.
Ayako Oshima Akiko Nishimura Toyofumi F. Chen‐Yoshikawa Shin‐ichi Harashima Teruya Komatsu Tomohiro Handa Akihiro Aoyama Koji Takahashi Masaki Ikeda Yohei Oshima Kohei Ikezoe Susumu Sato Maki Isomi Kenichiro Shide Hiroshi Date Nobuya Inagaki 《Clinical transplantation》2019,33(6)
Japanese patients with interstitial lung disease (ILD) sometimes die waiting for lung transplantation (LTx) because it takes about 2 years to receive it in Japan. We evaluated nutrition‐related factors associated with waiting list mortality. Seventy‐six ILD patients were hospitalized in Kyoto University Hospital at registration for LTx from 2013 to 2015. Among them, 40 patients were included and analyzed. Patient background was as follows: female, 30%; age, 50.3 ± 6.9 years; body mass index, 21.1 ± 4.0 kg/m2; 6‐minute walk distance (6MWD), 356 ± 172 m; serum albumin, 3.8 ± 0.4 g/dL; serum transthyretin (TTR), 25.3 ± 7.5 mg/dL; and C‐reactive protein, 0.5 ± 0.5 mg/dL. Median observational period was 497 (range 97‐1015) days, and median survival time was 550 (95% CI 414‐686) days. Survival rate was 47.5%, and mortality rate was 38.7/100 person‐years. Cox analyses showed that TTR (HR 0.791, 95% CI 0.633‐0.988) and 6MWD (HR 0.795, 95% CI 0.674‐0.938) were independently correlated with mortality and were influenced by body fat mass and leg skeletal muscle mass, respectively. It is suggested that nutritional markers and exercise capacity are important prognostic markers in waitlisted patients, but further study is needed to determine whether nutritional intervention or exercise can change outcomes. 相似文献
29.
Association between cardiovascular autonomic neuropathy and left ventricular hypertrophy in diabetic haemodialysis patients. 总被引:1,自引:1,他引:0
Masato Nishimura Tetsuya Hashimoto Hiroyuki Kobayashi Toyofumi Fukuda Koji Okino Noriyuki Yamamoto Naoto Nakamura Toshikazu Yoshikawa Hakuo Takahashi Toshihiko Ono 《Nephrology, dialysis, transplantation》2004,19(10):2532-2538
BACKGROUND: Patients with diabetic nephropathy are likely to have neurological complications including cardiovascular autonomic dysfunction, which is related to increased risk of mortality. We investigated whether cardiovascular autonomic neuropathy is associated with left ventricular hypertrophy (LVH) in diabetic haemodialysis patients. METHODS: Holter electrocardiography was carried out for 24 h with time and frequency domain analyses of heart rate variability in 154 diabetic (age 62+/-11 years) and 63 non-diabetic haemodialysis patients (62+/-10 years). The left ventricular mass index (LVMI) was determined by echocardiography. We used the percentage of differences exceeding 50 ms between adjacent normal RR intervals (pNN50) in time domain analysis and the power in the high-frequency range (HF: 0.15-0.40 Hz) in frequency domain analysis as indicators of parasympathetic activity. RESULTS: The mean LVMI was greater in diabetic than in non-diabetic patients (168+/-63 vs 144+/-54 g/m(2), P<0.01). LVMI inversely correlated with pNN50 (r = -0.270, P = 0.0007, n = 154) and HF (r = -0.277, P = 0.0005, n = 154) in diabetic patients, but not in non-diabetic patients. By multiple logistic analysis, LVH was strongly associated with pNN50 (odds ratio 0.088; 0, <2%; 1, >/=2%) and HF (odds ratio 0.058; 0, <500 ms(2); 1, >/=500 ms(2)) in diabetic patients. CONCLUSIONS: Impaired parasympathetic activity, which indicates cardiovascular autonomic neuropathy, was associated with the presence of LVH in diabetic haemodialysis patients. The co-existence of cardiovascular autonomic neuropathy and LVH may be one of the key factors for the high incidence of cardiovascular events in diabetic haemodialysis patients. 相似文献
30.
Yoshihisa Yamamoto Toshiro Fukami Tatsuo Koide Yoshinori Onuki Toyofumi Suzuki Koichi Metori Noriko Katori Yukio Hiyama Kazuo Tomono 《International journal of pharmaceutics》2014
In the present study, we performed comprehensive pharmaceutical evaluation among an original clobetasone butyrate (CLB) ointment product and three generic products. Although spherocrystal images were observed under a polarizing microscope for only Kindavate®, the original product, distribution of active and inactive ingredients was chemically equivalent between the original and generic medicine by the attenuated total reflection infrared spectroscopy. These results suggest that the spherocrystals observed in Kindavate® are composed of hydrocarbon. On GC/MS, it was revealed that linear alkanes having 25–27 carbon atoms are densely present in Sun White®, the base used in Kindavate®. On the other hand, linear alkanes having 22–31 carbon atoms were broadly distributed in most other white petrolatums. In the CLB ointment products, the distribution equivalent of linear alkane to Sun White® was observed only in Kindavate®. Thus, the GC/MS method is extremely useful for identification of white petrolatum used in the ointment. 相似文献