Studies on the Metabolic Fate of Leukotriene Antagonist ONO-1078. (1). Absorption, Distribution and Excretion after Single Administration to Rats.

Ishido, Masatsune; Shibakawa, Kimio; NAKAO, Yasuhiro; Sawada, Masafumi; Aishita, Hideki

doi:10.2133/dmpk.8.3

Cited by 4 publications

(4 citation statements)

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“…Drugs that open the blood brain barrier would cause extravasation of blood components from the brain capillary to the CNS because of the large difference between blood pressure (80 – 140 mm Hg) and intracranial pressure (7–15 mm Hg), thereby giving rise to adverse physical conditions in the patients. Since cysteinyl leukotriene receptors are present at the outside of the brain capillary, cysteinyl leukotriene receptor antagonists that do not, or only minimally, cross the blood brain barrier 6 should have no effect on the brain capillary. In fact, the present study demonstrated that montelukast, which is known as a pure cysteinyl leukotriene receptor antagonist, failed to inhibit the extravasation of both WBCs and cancer cells in the brain capillary.…”

Section: Discussionmentioning

confidence: 99%

Cysteinyl Leukotriene Receptor Antagonists Inhibit Tumor Metastasis by Inhibiting Capillary Permeability

Nozaki

Yoshikawa

Ishitani³

et al. 2010

Keio J. Med.

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We explored the possibility of the cysteinyl leukotriene receptor antagonists, pranlukast and montelukast, preventing tumor cell migration through both cerebral and peripheral capillaries. To study tumor cell migration through brain capillaries, male Fisher rats were cannulated via the cisterna magna under pentobarbital anesthesia. RCN9 cells labeled with a fluorescent marker PKH67 were intravenously administered following arachidonic acid administration into the subarachnoid space, and specimens of the central nervous system were collected every 30 min for 8 h. Arachidonic acid increased the fluid volume with elevated white blood cell and RCN9 cell counts. When given 2 h before arachidonic acid administration, pranlukast, but not montelukast, reduced the fluid volume and inhibited white blood cell and RCN9 cell extravasation through the brain capillary. In addition, a Lewis lung carcinoma metastasis model in mice was used to study the inhibitory effect of pranlukast and montelukast against cancer cell extravasation through general capillaries. When mice were given food containing either pranlukast or montelukast, immediately after paw amputation, tumor metastasis was prevented by both drugs, and their survival was prolonged. These results show that pranlukast can inhibit tumor cell migration through both the brain and peripheral capillaries, whereas montelukast inhibits tumor cell migration only in the peripheral capillaries.

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Section: Discussionmentioning

confidence: 99%

Cysteinyl Leukotriene Receptor Antagonists Inhibit Tumor Metastasis by Inhibiting Capillary Permeability

Nozaki

Yoshikawa

Ishitani³

et al. 2010

Keio J. Med.

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“…The dissolution rate and saturated solubility of PLH in SMEDDS increased in association with the increase of pH values, which were similar to the results of a previous report. 26 However, PLH from plain PLH was not detected in SGF (pH 1.2) and PBS (pH 4.0). In each test media, the initial dissolution rate of PLH from SMEDDS was significantly faster than that of PLH from plain PLH.…”

Section: Dovepressmentioning

confidence: 97%

“…26 Thus, the improvement in the initial dissolution Note: Each value represents the mean ± SD (n = 3). Abbreviations: AUC, area under the curve; C max , peak plasma concentration; MRT last , mean residence time; PLH, pranlukast hemihydrate; SMEDDS, selfmicroemulsifying drug delivery system; T max , the time to reach C max .…”

Section: Dovepressmentioning

confidence: 99%

Self-microemulsifying drug-delivery system for improved oral bioavailability of pranlukast hemihydrate: preparation and evaluation

Baek¹,

Lee²,

Cho³

et al. 2013

IJN

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Abstract:The purpose of the present investigation was to develop and evaluate a selfmicroemulsifying drug delivery system (SMEDDS) for improving the oral absorption of a pranlukast hemihydrate (PLH), a very poorly water-soluble drug. An efficient self-microemulsifying vehicle for PLH was selected and optimized using solubility testing and phase diagram construction. The formulations were characterized by assessing self-emulsification performance, droplet size analysis, in vitro drug release characteristics and formulation stability studies. Optimized formulations for in vitro dissolution and bioavailability assessment were Triethylcitrate (TEC; 10%), Tween 20 (50%), Span 20 (25%), triethanolamine (5%), and benzyl alcohol (10%). The SMEDDS readily released the lipid phase to form a fine oil-in-water microemulsion with a narrow distribution size. Saturated solubilities of PLH from SMEDDS in water, pH 4.0 and 6.8, were over 150 times greater than that of plain PLH. The release of 100% PLH from SMEDDS was considerably greater compared to only 1.12% in simulated intestinal fluid (pH 6.8) from plain PLH after 2 hours. The PLH suspension with 0.5% sodium carboxymethylcellulose or 3% PLH-loaded SMEDDS was administrated at a dose of 40 mg/kg as PLH to fasted rats. The absorption of PLH from SMEDDS resulted in about a threefold increase in bioavailability compared with plain PLH aqueous suspension. Our studies illustrated that the potential use of the new SMEDDS can be used as a possible alternative to oral delivery of a poorly water-soluble drug such as PLH.

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“…AUC of the particles prepared by the high-pressure homogenizer with Hsp-G was 2.2-fold that of the untreated PLH. It was reported that the absorption site of PLH is in the upper part of the gastrointestinal tract (Ishido et al, 1993). Thus, the improvement in the initial dissolution rate is especially significant for improvement of the gastrointestinal absorption of pranlukast (Chono et al, 2008).…”

Section: Introductionmentioning

confidence: 98%

α-Glucosyl hesperidin induced an improvement in the bioavailability of pranlukast hemihydrate using high-pressure homogenization

Uchiyama

Tozuka

Asamoto

et al. 2011

International Journal of Pharmaceutics

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Studies on the Metabolic Fate of Leukotriene Antagonist ONO-1078. (1). Absorption, Distribution and Excretion after Single Administration to Rats.

Cited by 4 publications

References 0 publications

Cysteinyl Leukotriene Receptor Antagonists Inhibit Tumor Metastasis by Inhibiting Capillary Permeability

Cysteinyl Leukotriene Receptor Antagonists Inhibit Tumor Metastasis by Inhibiting Capillary Permeability

Self-microemulsifying drug-delivery system for improved oral bioavailability of pranlukast hemihydrate: preparation and evaluation

α-Glucosyl hesperidin induced an improvement in the bioavailability of pranlukast hemihydrate using high-pressure homogenization

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