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991.
992.
Okimoto K Tokunaga Y Ibuki R Irie T Uekama K Rajewski RA Stella VJ 《International journal of pharmaceutics》2004,286(1-2):81-88
The purpose of this study was to investigate the general application of a controlled-porosity osmotic pump tablet (OPT) utilizing (SBE)7m-beta-CD as both a solubilizer and an osmotic agent for drugs with varying physical properties. OPTs utilizing (SBE)7m-beta-CD were prepared for five poorly soluble and two highly water-soluble drugs. The Japanese Pharmacopoeia dissolution method was used to study the drug and (SBE)7m-beta-CD release from the OPTs. The drug concentration in the OPT core after the OPT was placed in the release medium for two hours was assayed gravimetrically and by HPLC. An appropriate composition ratio (ACR) of (SBE)7m-beta-CD to drug at which drug release from the OPT was complete and pH-independent within the physiological pH range of the GI tract was determined for each drug. The ACR values correlate to the drug concentration in the OPT core when the OPTs were placed in the release medium for two hours. The release profiles of prednisolone (a poorly water-soluble drug) and sodium chloride (a water-soluble compound) from the OPTs were almost the same as that of (SBE)7m-beta-CD. Also, the release rate of each drug per unit membrane surface area from the OPTs was similar, regardless of the differences in drug solubility. The present results confirmed that (SBE)7m-beta-CD serves as both a solubility modulator and as an osmotic pumping agent for OPTs, from which the release rate of both water-soluble and poorly water-soluble drugs can be controlled. 相似文献
993.
Expression Levels of Renal Organic Anion Transporters (OATs) and Their Correlation with Anionic Drug Excretion in Patients with Renal Diseases 总被引:3,自引:0,他引:3
Sakurai Y Motohashi H Ueo H Masuda S Saito H Okuda M Mori N Matsuura M Doi T Fukatsu A Ogawa O Inui K 《Pharmaceutical research》2004,21(1):61-67
PURPOSE: Because the urinary excretion of drugs is often decreased in renal diseases, dosage regimens are adjusted to avoid adverse drug reactions. The aim of present study was to clarify the alteration in the levels of renal drug transporters and their correlation with the urinary drug excretion in renal diseases patients. METHODS: We quantified the mRNA levels of human organic anion transporters (hOATs) by real-time polymerase chain reaction and examined the excretion of the anionic drug, cefazolin, in renal disease patients. Moreover, transport of cefazolin by hOAT1 and hOAT3 were examined using HEK293 transfectants. RESULTS: Among four hOATs, the level of hOAT1 mRNA was significantly lower in the kidney of patients with renal diseases than in the normal controls. The elimination constant of cefazolin showed a significant correlation with the values of phenolsulfonphthalein test and mRNA levels of hOAT3. The uptake study using HEK293 transfectants revealed that cefazolin and phenolsulfonphthalein were transported by hOAT3. CONCLUSIONS: These results suggest that hOAT3 plays an important role for anionic drug secretion in patients with renal diseases and that the expression levels of drug transporters may be related to the alteration of renal drug secretion. 相似文献
994.
The cardiac toxicity of amitriptyline and the effect of the light schedule on it were studied in chick embryos. Fertilized eggs of White Leghorns were incubated under dark conditions and investigated, on two occasions, in the light phase and in the dark phase. Amitriptyline was injected into the air sac of fertilized eggs on the 16th day of incubation. Electrocardiograms were recorded 0 to 60 min after the injection. After the administration of amitriptyline 1 mg/egg in the light phase, the heart rate did not differ compared with that in controls. However, the heart rate was significantly decreased by the administration of amitriptyline 2.5 mg/egg and 5 mg/egg in the light phase. The heart rate was significantly decreased by the administration of amitriptyline 1 mg/egg under dark conditions. In addition, arrhythmia was produced by the administration of amitriptyline under dark conditions. These findings indicate that manipulation of the light schedule has a marked influence on the toxicity of amitriptyline in chick embryos. 相似文献
995.
Sato Y Akiyama H Suganuma H Watanabe T Nagaoka MH Inakuma T Goda Y Maitani T 《Biological & pharmaceutical bulletin》2004,27(7):978-984
Feed containing beta-carotene was administered orally to BALB/c mice immunized intraperitoneally with ovalbumin (OVA) for approximately 1 month. The titers of OVA-specific IgE, OVA-specific IgG1 and OVA-specific IgG2a in the mouse sera were determined. The OVA-specific IgE titer and OVA-specific IgG1 titer by mice fed beta-carotene were significantly inhibited. On the other hand, the OVA-specific IgG2a titer in mice fed beta-carotene was significantly greater than those of control mice. The OVA-specific IgE suppression of beta-carotene feeding was dose-dependent. We also examined the effect of fed beta-carotene on active systemic anaphylaxis. Feeding beta-carotene to mice immunized with OVA inhibited the immediate reduction of the body temperature induced by antigen stimulation. Furthermore, the increase in serum histamine in the mice fed beta-carotene under active systemic anaphylaxis was lower than in controls. We then examined the pattern of cytokine production by spleen cells from mice followed by restimulation with OVA in vitro. The spleen cells from the mice fed beta-carotene produced more IFN-gamma, IL-12 and IL-2 than those from the control group. In contrast, the spleen cells from the mice fed beta-carotene produced less IL-4, IL-5, IL-6, IL-10 than those from the control group. Furthermore, analysis of IFN-gamma mRNA levels of the splenocytes using the real-time quantitative RT-PCR technique revealed higher levels in the splenocytes from the mice fed beta-carotene. These findings suggest that feeding beta-carotene improves the helper T cell (T(H))1-T(H)2 balance, inhibiting specific IgE and IgG1 production and antigen-induced anaphylactic response. 相似文献
996.
The entering of indium-111 and iron-59 into the hepatocytes from partially hepatectomized rats differ from that of gallium-67 总被引:1,自引:0,他引:1
Sato R Abe S Yamada Y Toyama D Ohtake Y Sato N Ohkubo Y 《Biological & pharmaceutical bulletin》2004,27(8):1193-1196
We recently suggested that the transferrin (Tf)-gallium-67 (67Ga) complex dissociated on the surface of the hepatocytes after partial hepatectomy and free 67Ga bound to heparan sulfate in the extracellular matrix. In the present study, we investigated whether the entering of indium-111 (111In) and iron-59 (59Fe) with high affinity to transferrin differed from the entering of 67Ga by the hepatocytes after partial hepatectomy. 111In was almost taken by the plasma and little taken by the red blood cell. On the other hand, the uptake of 59Fe by the red blood cell was higher than plasma. The uptake of 59Fe by the bone marrow was significantly higher than that of 111In. The uptake of 111In and 59Fe by the liver tissue was reached a maximum 2 d after partial hepatectomy but the uptake ratio of 111In was lower than that of 59Fe. We suspected that the uptake of 59Fe by the liver tissue was the highest because of the high binding affinity of Tf-59Fe to Tf-receptor. The entering of 111In and 59Fe into the hepatocytes was also reached a maximum 2 d after partial hepatectomy but the ratio of 59Fe was slightly lower than that of 111In. These results suggested that the binding affinity to Tf could have played a crucial role in the differences of the entering of 111In, 59Fe and 67Ga into the hepatocytes of partially hepatectomized rats. 相似文献
997.
Taura K Naito E Ishii Y Mori MA Oguri K Yamada H 《Biological & pharmaceutical bulletin》2004,27(1):56-60
The effects of cytochrome P450 (P450, CYP) ligands and permeabilization of microsomes on 3-hydroxybenzo(a)pyrene [3-OH-B(a)P] glucuronidation mediated by rat hepatic microsomes were studied. While the UDP-glucuronosyltransferase (UGT) activity with non-permeabilized microsomes from 3-methylcholanthrene (MC)-treated rats was markedly reduced by alpha-naphthoflavone (NF), this inhibitor had hardly any effect when permeabilized microsomes were used in which the inhibitor was expected to have easy access to UGT. Kinetic analysis indicated that the inhibitory effect of alpha-NF is competitive. These results suggest that a UGT isoform(s) involved in 3-OH-B(a)P glucuronidation is interfered by a CYP1A inhibitor via a mechanism dependent on the intact nature of microsomal membranes in MC-treated rats. It is likely that P450 functions as a substrate transporter for some isoforms of UGT via possible interactions between UGT and P450. 相似文献
998.
999.
Inoue S Oshima Y Nagai K Yamamoto T Go J Kai N Honjo T 《Environmental toxicology and chemistry / SETAC》2004,23(5):1276-1281
We examined the effect of tributyltin (TBT) on reproduction of the pearl oyster (Pinctada fucata martensii). In a maternal exposure test, five female pearl oysters were exposed to TBT at measured concentrations of 0 (control), 0.092, or 0.191 microg/L at 25 degreesC for one week, and the embryo developmental success (the ratio of normal D-larvae to all larvae) was measured. The embryo developmental success was significantly decreased in the 0.191-microg/L treatment group (65.5%) compared to that in the control group (82.5%; p = 0.031). Concentrations of TBT in the ovary reached 0.088 microg/g in the 0.191-microg/L treatment group. In a waterborne exposure test, inseminated eggs were exposed to TBT at measured concentrations of 0 (control), 0.020, 0.045, 0.091, 0.192, or 0.374 microg/L for 24 h. The embryo developmental success also was significantly decreased in the 0.192-microg/L treatment group (78.3%; p = 0.020) and no development at all was observed in the 0.374-microg/L treatment group compared with that in the control group (95.4%). These results clearly demonstrate that TBT accumulating in the bodies of bivalves has the potential to inhibit reproduction. 相似文献
1000.