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Dive into the research topics where Hiroshi Yoshikawa is active.

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Featured researches published by Hiroshi Yoshikawa.


Journal of Chromatography B: Biomedical Sciences and Applications | 1990

Determination of a novel potent immunosuppressant (FK-506) in rat serum and lymph by high-performance liquid chromatography with chemiluminescence detection

Kanji Takada; Mamoru Oh-Hashi; Hiroshi Yoshikawa; Shozo Muranishi; Michihisa Nishiyama; Hiromitsu Yoshida; Takehisa Hata; Hirokazu Tanaka

FK-506 (I) a macrolide antibiotic extracted from the fermentation broth of Streptnmyces tmkuhaensis [ 11, has been shown to have strong immunosuppressive activity against a mixed lymphocyte reaction (MLR) [2]. In addition, intramuscular injection of I at 1 mg/kg per day will prolong graft survival in heterotropic cardiac allotransplantation in rats [3]. The pharmacological mechanism is considered to be a suppression of both interleukin 2 (IL-2) and IL-2 receptor expression on T cells [4]. The pharmacological activity of 1 is reported to be cu. 100 times greater than that of cyclosporin A (CyA) [5,6]. To perform a bioavailability study of I in both humans and dogs, an enzyme immunoassay (EIA) method has been established and used for the determination of plasma levels of I [7]. However, we cannot deny the existence of the crossreactivity of the antisera with some of the circulating metabolites of 1, as suggested from a pharmacokinetic study with CyA [8.9]. A biopharmaceutical study using EIA [8] showed that the amounts of I excreted into both the urine and the bile of dogs is less than 1% of the injected dose. Therefore, the main elimination pathway of I is thought to be the metabolism in the body. Thus, a new assay method specific to I in the plasma is needed to perform basic pharmacokinetic studies in experimental animals. In addition, we have been studying the relation-


Pharmaceutical Research | 1986

Effect of Oleic Acid Vesicles on Intestinal Absorption of Carboxyfluorescein in Rats

Masahiro Murakami; Hiroshi Yoshikawa; Kanji Takada; Shozo Muranishi

The effect of oleic acid vesicles (ufasomes) on the intestinal absorption of entrapped carboxyfluo-rescein (CF) was investigated by an in situ closed–loop method in rats. Entrapment of CF in ufasomes enhanced the absorption of CF at the earlier stage following intraduodenal administration, and the threshold concentration of the fatty acid for promoting the absorption of CF was approximately 8 mM. The absorption of CF from the large intestine was promoted much more effectively than from the small intestine. These studies suggest that ufasomes have potential as carriers for the oral administration of poorly absorbable drugs.


Pharmaceutical Research | 1986

Enhanced selective lymphatic delivery of cyclosporin A by solubilizers and intensified immunosuppressive activity against mice skin allograft

Kanji Takada; Hiroyuki Yoshimura; Hiroshi Yoshikawa; Shozo Muranishi; Tadaki Yasumura; Takahiro Oka

The absorption and lymphatic delivery of a new immunosuppressive drug, cyclosporin A (CsA), were studied in rats by administering CsA orally after solubilization with HCO-60 (polyoxyethylated hydrogenated castor oil), sugar ester, and oils. After the administration of solubilized CsA (7 mg/kg) to rats with thoracic lymph duct cannulas, both plasma and lymph CsA levels were measured over 6 hr. The lymph CsA levels were strongly affected by the solubilizers. The rank order of the solubilizers in enhancing lymph absorption was HCO-60 (57 µg/ml) > sugar ester (46 µg/ml) > sesame oil (3.5 µg/ml) > linoleic acid (0.4 µg/ml), where the parentheses show the maximum lymph CsA levels. Plasma CsA levels were below 2 µg/ml in each group of animals and were barely altered by the solubilizers. These results support the selective lymphatic delivery of CsA with solubilizers such as HCO-60 and sugar ester. The immunosuppressive activity of CsA (1 mg/kg) solubilized with HCO-60 was nearly equivalent to the sesame oil solution with 7 to 15 mg/kg CsA in the skin-allograft mice model.


Pharmaceutical Research | 1985

Potentiation of enteral absorption of human interferon alpha and selective transfer into lymphatics in rats

Hiroshi Yoshikawa; Kanji Takada; Yu-Ichiro Satoh; Norio Naruse; Shozo Muranishi

Enhancement of human leucocyte interferon (HuIFN-α) absorption from rat large intestine was studied with the aid of lipid, surfactant and lipid-surfactant mixed micelles. Neither the emulsified lipid (linoleic acid) nor the surfactant (HCO60, polyoxyethylated [60 moles] hydrogenated castor oil) alone were able to enhance the absorption of HuIFN-α. However, linoleic acid-HCO60 mixed micelles enhanced the absorption of HuIFN-α from the large intestine. Highly selective delivery of HuIFN-α into the lymphatics compared to the blood was also observed.


International Journal of Pharmaceutics | 1985

Selective transfer of 1-hexylcarbamoyl-5-fluorouracil into lymphatics by combination of β-cyclodextrin polymer complexation and absorption promoter in the rat

Yuji Kaji; Kaneto Uekama; Hiroshi Yoshikawa; Kanji Takada; Shozo Muranishi

Abstract The β-cyclodextrin polymer (polyβCD) was used as a candidate for a macromolecular carrier of a bifunctional delivery system, and the applicability of this new biodegradable polymer was studied using 1-hexylcarbamoyl-5-fluorouracil (HCFU) by administering into the lumen of the large intestine, and into the abdominal cavity. Bifunctional delivery system (mixed micelles + HCFU-polyβCD complex) increased the selective transfer of HCFU into the lymphatics after the large intestinal administration. On the other hand, after the intraperitoneal administration, we found that the administration of HCFU-polyβCD complex without mixed micelles increased the selective transfer of HCFU into the lymphatics. The selective transfer into the lymphatics was found by administration of drug into the abdomen rather than into the large intestine. These results suggest that such a new bifunctional delivery system will be a powerful tool in the field of antitumor chemotherapy.


Archive | 1986

Enhanced Absorption and Lymphatic Transport of Macromolecules via the Rectal Route

Shozo Muranishi; Kanji Takada; Hiroshi Yoshikawa; Masahiro Murakami

The rectal route has long been known as a specific absorption means for the delivery of lipophilic small molecules. In general rectal delivery exhibits several advantages as summarized in Table 1.


Pharmaceutical Research | 1986

Development of Interferon Suppositories. I. Enhanced Rectal Absorption of Human Fibroblast Interferon by Fusogenic Lipid via Lymphotropic Delivery in Rats

Hiroshi Yoshikawa; Kanji Takada; Yu-Ichiro Satoh; Norio Naruse; Shozo Muranishi

We attempted to enhance the rectal absorption of human fibroblast interferon (HuIFN-β) in rats by the administration of suppositories containing fusogenic lipid and a nontoxic surfactant. Suppositories containing either the lipid (linoleic acid) or the surfactant [HCO60; polyoxyethylated (60 mol) hydrogenated castor oil] alone failed to enhance the absorption of HuIFN-β. However, suppositories containing both linoleic acid and HCO60 facilitated the rectal absorption of HuIFN-β. The absorbed HuIFN-β was selectively delivered via the lymph.


Journal of Pharmacy and Pharmacology | 1997

Biodistribution of Cyclosporin Encapsulated in Liposomes Modified with Bioadhesive Polymer

Yukako Yoshikawa; Masaya Miyazaki; Takeshi Houjou; Yutaka Komuta; Hiroshi Yoshikawa; Kanji Takada

The purpose of this investigation was to study the possibility of renewing the immunosuppressive activity of cyclosporin by formulating the compound in liposomes modified with bioadhesive polymers. The liposomes prepared were evaluated both pharmacokinetically and pharmacodynamically. Tissue distribution and plasma pharmacokinetics of cyclosporin and model dye, sudan black, which is as hydrophobic as cyclosporin, were studied in rats after intravenous infusion (10 mg kg−). The immunosuppressive efficacy of liposomal cyclosporin preparations was studied in the allogenic rat‐heart‐transplantation model, where cyclosporin therapy (10 mg kg−) continued for one week.


International Journal of Pharmaceutics | 1988

Increased systemic availability of cyclosporin A by formulation design: pharmacokinetic consideration on its transport

Kanji Takada; Yoshihiro Furuya; Hiroshi Yoshikawa; Shozo Muranishi; Tadaki Yasumura; Takahiro Oka

Abstract The systemic availability of cyclosporin A (CyA) from two different oral formulations was investigated in rats in relation to the lymphatic transport of CyA. The two test oral CyA formulations were a well-solubilized solution with a pharmaceutical additive, polyoxy 60 caster oil (HCO-60), and an olive oil formation. Each formulation was administered orally to two groups of 4 rats. After oral administration of the HCO-60 formulation, 7 mg/kg, the peak plasma CyA level and the area under the curve (AUC) were 1.5 times higher than obtained from the olive oil formulation. To clarify the contribution of the two absorption routes, portal and lymphatic, on the systemic availability of CyA, a pharmacokinetic study was performed by administering CyA to two more groups of 3 rats by two different administration routes, intraportal (i.p.) infusion and intravenous (i.v.) injection. The mean AUC after i.p. infusion, 7 mg/kg, was 11.32 ± 0.85(S.E.M.) μg · h/ml and after i.v. injection, 3.5 mg/kg, was 8.74 ± 0.85 (S.E.M.) μg · h/ml. By analyzing these results with a physiologic pharmacokinetic model containing the liver and gastrointestinal (GI) tissue as metabolic eliminating organs for CyA, the increased systemic availability of CyA by formulation design was revealed to be due to increased absorption from the GI tract and the main transport route after being absorbed into the GI cells was revealed to be the portal venous system.


International Journal of Pharmaceutics | 1990

PHARMACOKINETIC ANALYSIS OF PLASMA DRUG LEVEL DATA OBTAINED FROM A TRANSDERMAL THERAPEUTIC SYSTEM WITH A COMPLEX ABSORPTION MODEL

Kanji Takada; Hiroshi Yoshikawa; Shozo Muranishi

Abstract The phenomenon of a pseudo steady state in the plasma drug level vs time curve observed after the administration of drugs to human skin with transdermal therapeutic systems (TTS) is analyzed with a complex absorption model. The model is based on the following assumptions: (1) drug disposition in the body may be described by kinetics based on a one-compartment model; (2) the process of drug absorption initially proceeds at a constant rate according to (zero-order) absorption kinetics but after a finite time, t1, the zero-order absorption rate decreases with time in a first-order manner. This model requires three additional parameters to the conventional pharmacokinetic one-compartment model: namely, kd (h−1, the first-order decreasing rate constant for zero-order absorption, T1 (h), the time at which the zero-order absorption process ceases and T2 (h), the time of removal of TTS from the application site, i.e. the skin. The analysis based on this complex absorption model was performed for the plasma drug concentration vs time data obtained after the administration of TTS containing isosorbide dinitrate (ISDN), nitroglycerin (NTG) or clonidine. Equations describing the plasma drug concentration vs time profile are provided and a ‘peeling’ method to obtain the initial estimates of the parameters is described. The final pharmacokinetic parameter values were determined via nonlinear regression analysis of the plasma drug level vs time data using the above equations. The convergence and fitting of the data were excellent and the results of fitting are in support of the validity of this complex model analysis.

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Kanji Takada

Kyoto Pharmaceutical University

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Shozo Muranishi

Kyoto Pharmaceutical University

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Mamoru Oh-Hashi

Kyoto Pharmaceutical University

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Masahiro Murakami

Kyoto Pharmaceutical University

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Tadaki Yasumura

Kyoto Prefectural University of Medicine

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Takahiro Oka

Kyoto Prefectural University of Medicine

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Yoshihiro Furuya

Kyoto Pharmaceutical University

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Hiroyuki Yoshimura

Kyoto Pharmaceutical University

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