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Biomedical subjects

T Nishihata

Publications and source records attributed to T Nishihata.

At least 19 recordsLinked to original sources
PubMed1995

Bioavailability of bropirimine 250 mg tablet in dogs: effect of food.

The postprandial effect on the bioavailability of bropirimine in dogs after oral administration of bropirimine tablets (Bropirimine 250 mg Tablet) was investigated. At a dose of 500 mg bropirimine (two tablets of bropirimine 250 mg), the maximum plasma concentration under the postprandial condition was about twice that observed under the fasting condition, and the area under the plasma concentration vs time curve under the postprandial condition was also twice that under the fasting condition. The absolute oral bioavailabilities of bropirimine were 41.1% under the fasting condition and 83.5% under the postprandial condition. It is considered that the longer gastric residence time and larger volume of the gastric fluid induced by food-intake caused the increase in dissolution of bropirimine which increased the bioavailability after oral dosing of bropirimine 250-mg tablets.

Absorption↗
PubMed1995

Small intestinal absorption of bropirimine in rats and effect of bile salt on the absorption.

The intestinal absorption characteristics of a poorly water-soluble drug, bropirimine, were investigated by the in-situ small intestinal loop method using male Sprague-Dawley rats. Bropirimine in solution was well absorbed in the overall small intestine, following first-order kinetics. The rate determining step for the disappearance of bropirimine from the small intestinal loop after dosing in the suspension was the dissolution process from suspension. Bropirimine was solubilized by sodium glycocholate. The disappearance of bropirimine from the small intestinal loop was suppressed by sodium glycocholate contained in the solution, because of the loss of thermodynamic activity of bropirimine after its involvement in the micellar complex, not by the direct effect of bile salt on the permeability of intestinal mucosa. The disappearance of bropirimine was also suppressed by sodium glycocholate contained in the suspension. The suppression by sodium glycocholate seemed to be caused by the greater influence of sodium glycocholate on the thermodynamic activity of bropirimine than on the dissolution from suspension.

Adjuvants, Immunologic↗
PubMed1994

Enhanced rectal absorption of itazigrel formulated with polysorbate 80 micelle vehicle in rat: role of co-administered esterase.

We investigated the effect of esterase on rectal absorption in the rat of itazigrel using polysorbate 80 (PS-80) micelle as a vehicle to overcome the poor aqueous solubility of itazigrel. The itazigrel formulation prepared with PS-80 increased the absorption compared with a 0.25% carmellose sodium suspension, probably by supplying the itazigrel solute to keep a high concentration at the epithelial surface. When esterase was co-administered with the formulations containing PS-80, the absorption of itazigrel from rat rectum was accelerated further, by rapid release of itazigrel from the micelle vehicle after enzymatic degradation of the PS-80 micelle.

Absorption↗
PubMed1994

Inhibitory effect of clindamycin on production of beta-lactamase in beta-lactam-resistant bacteria.

The inhibitory effect of clindamycin on beta-lactamase biosynthesis was investigated in beta-lactam resistant bacteria with inducible and/or constitutive production of the enzyme(s). Clinical isolates of Enterobacter cloacae (E. cloacae) and Pseudomonas aeruginosa (P. aeruginosa) were examined. Three strains of each, against which sulbactam at 8 micrograms/ml reduced the minimum inhibitory concentration (MIC) of cefoperazone (CPZ) at least 4 fold, were studied in greater detail. Although clindamycin had no appreciable effect on bacteria growth at concentrations up to 50 micrograms/ml, it suppressed inducible beta-lactamase biosynthesis almost completely at a concentration of 20 micrograms/ml. There was also a significant reduction of constitutive enzyme biosynthesis by clindamycin at 50 micrograms/ml. Thus, it was estimated that a high concentration of clindamycin was required to suppress beta-lactamase biosynthesis in beta-lactamase producing bacteria of the constitutive type.

Anti-Bacterial Agents↗
PubMed1993

Percutaneous permeation of basic compounds through shed snake skin as a model membrane.

Relationships between the in-vitro permeability of basic compounds through shed snake skin as a suitable model membrane for human stratum corneum and their physiochemical properties were investigated. Compounds with low pKa values were selected to compare the permeabilities of non-ionized forms of the compounds. Steady-state penetration was achieved immediately without a lag time for all compounds. Flux rate and permeability coefficient were calculated from the steady-state penetration data and relationships between these parameters and the physicochemical properties were investigated. The results showed that permeability may be controlled by the lipophilicity and the molecular size of the compounds. Equations were developed to predict the permeability from the molecular weights and the partition coefficients of basic compounds.

Animals↗
PubMed1993

Use of enzymatic activity for design of orally administered enteric dosing forms.

Liquid and semi-solid enteric dosage forms were prepared by entrapping drug with an appropriate partition coefficient in a lipid base vehicle which would then be released by the action of intestinal enzymes. Lipid ester derivatives such as glyceryl monocaprylate and polysorbate 80 were used as vehicles. These vehicles readily dissolved the poorly water-soluble compounds used in the study, itazigrel, indomethacin and the dye, sudan II, and were digested by lipase and esterase, releasing the test drugs with time profiles similar to those observed in dissolution studies. The vehicles released little or only a small amount of the drugs into aqueous medium in the absence of an appropriate enzyme. The enzyme-sensitive enteric vehicles when containing sudan II did not release the dye in the stomach of rats after oral administration, but released significant amounts of the dye in the small intestine.

Animals↗
PubMed1993

Evaluation of enteric coated tablet sensitive to pancreatic lipase. II. In vivo evaluation.

Plain tablets containing a model drug, sulfamethizole (SMZ), were coated with triolein (TO), trilaurin (TL) and ethylcellulose (EC). The biological behavior of the coated tablets (TOTL-Tab), which are pH independent and sensitive to pancreatic lipase, was investigated in humans. Results of the administration of the tablets with or without an antacid, under fasting and non-fasting conditions, and at 0.5 h before and 0.5 h after meals, were examined. A comparison of the in vivo behavior of SMZ after the administration of these tablets was done using the following data: the lag time of urinary excretion (Ulag), the total urinary recovery percentage (X infinity u), and the mean residence time after Ulag (MRTaf). A typical pH-sensitive tablet coated by cellulose acetate phthalate (CAP-Tab) was used as a reference. For the administration of a CAP-Tab alone, the Ulag obtained under both the non-fasting and fasting condition was longer than that of the plain tablet. However, Ulag after the administration of a CAP-Tab with an antacid became considerably shorter. This lag time was about the same as that obtained from the plain tablet, regardless of food ingestion. The obtained CAP-Tab MRTaf and X infinity u values were not significantly different in comparison to the plain tablets. Under the non-fasting condition, Ulag, MRTaf and X infinity u of TOTL-Tab were not affected by the co-administration of an antacid, and these values were virtually the same as those obtained from a CAP-Tab without an antacid. The urinary excretion data obtained after the administration of TOTL-Tab alone under fasting was analogues to the non-fasting case.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

The effect of serum Ca2+ compensation on the efficacy of chlorpropamide in alloxan-diabetic rabbits.

A decrease in serum Ca2+ concentration was observed in alloxan-diabetic rabbits, with recovery of serum Ca2+ levels achieved following insulin therapy. This suggested that the diabetic condition directly relates to the decrease in serum Ca2+ levels. The efficacy of chlorpropamide in alloxan-diabetic rabbits after intravenous injection (150 mumol kg-1) was less than that in normal rabbits as measured by the serum insulin levels, and the efficacy did not change when the dose was increased. However, compensation of serum Ca2+ levels in alloxan-diabetic rabbits caused an increase in the efficacy of chlorpropamide observed as an increase in serum insulin and a decrease in serum glucose levels.

Animals↗
PubMed1991

In vitro transport of sodium diclofenac across rat abdominal skin: effect of selection of oleaginous component and the addition of alcohols to the vehicle.

The in vitro percutaneous transport of sodium diclofenac from various oil vehicles was examined using rat abdominal skin as a model skin membrane. The overall transport of diclofenac through the skin from the oleaginous vehicles was very poor because of a poor solubility of sodium diclofenac in nonpolar oils. To increase the solubility and the permeability of sodium diclofenac, ethanol and n-octanol were added to each oil (designated as the formulated vehicles). The addition of ethanol and n-octanol to the nonpolar vehicles resulted in an extreme increase in drug solubility in each vehicle, with a remarkable increase in the permeation of diclofenac. The effects of oil components in the formulated vehicle on the permeation of diclofenac across the skin were in the following order: squalane greater than or equal to squalene greater than liquid paraffin greater than middle chain triglyceride greater than olive oil greater than castor oil. In order to clarify the reason for the differences in permeation of diclofenac from these formulated vehicles, the release of diclofenac and n-octanol from these vehicles in vitro was studied. The release rates of n-octanol from the formulated vehicles were in the following order: liquid paraffin greater than squalene greater than or equal to squalane greater than middle chain triglyceride greater than or equal to olive oil greater than castor oil. On the other hand, a linear correlation was observed between the initial release rate of diclofenac from the formulated vehicle and the in vitro permeation of diclofenac through the vehicle to the skin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

In vitro percutaneous transport of sodium diclofenac and diclofenac from oleaginous vehicle.

The penetration enhancement of sodium diclofenac and diclofenac by alcohols with various alkyl chains (C8 to C14) was evaluated by the steady state flux of diclofenac through rat abdominal skin. Decanol showed the greatest effect in this series. A more remarkable enhancing effect of the alcohols was observed in sodium diclofenac than in diclofenac. Diclofenac can penetrate through the ethylene-vinyl acetate membrane as a lipoid model membrane, but sodium diclofenac can not. Decanol enhanced the penetration of phenol red being dependent on its concentration in the vehicle. Therefore, decanol may interact with lipoid components of the skin and increase the aqueous pathway in the skin. These results indicate that sodium diclofenac and diclofenac may be penetrated through partially different pathways.

Animals↗
PubMed1990

Combined effect of alcohol and urea on the in vitro transport of indomethacin across rat dorsal skin.

An aqueous gel, prepared with hydrogenated soya phospholipid, increased the in vitro transport of indomethacin across rat dorsal skin. The addition of various alkanols further accelerated the transport, with an increasing effect as the chain length of the alkanol increased. The addition of urea alone did not significantly affect the transport of indomethacin. However, the addition of urea markedly accelerated the transport of indomethacin when included in an aqueous gel containing an alkanol such as 1-octanol, 1-decanol, or 1-dodecanol. Thus, it appears that a combination of urea and these alkanols strongly enhances the transdermal absorption of indomethacin. Urea appears to accelerate enhanced drug transport into the stratum corneum by a mechanism involving the transport of urea enhanced by these alkanols.

Alcohols↗
PubMed1990

A method to predict the percutaneous permeability of various compounds: shed snake skin as a model membrane.

Penetration of various compounds through shed snake skin was measured in vitro to examine the effect of lipophilicity and molecular size of a compound on permeability through this model membrane. The permeabilities were found to be controlled by the lipophilicity and the molecular size of the permeant. The smaller and the more lipophilic the compound, the greater the permeability. Equations have been developed to predict the permeability from the molecular weight and the distribution coefficient of a compound. Further, the lipophilicity of shed snake skin is similar to that of human skin and the response of shed snake skin to the molecular size of a permeant is more similar to human skin than to hairless mouse skin. Considering the similarities between shed snake skin and human stratum corneum in terms of structure, composition, and permeability characteristics, the same considerations may apply to permeability through human stratum corneum.

Animals↗
PubMed1990

Use of shed snake skin as a model membrane for in vitro percutaneous penetration studies: comparison with human skin.

The potential usefulness of shed snake skin as a model membrane for transdermal research was examined. There are similarities between shed snake skin and human stratum corneum in terms of structure, composition, lipid content, water permeability, etc. The permeability of various compounds and the contribution of several functional groups to the permeability were also found to be similar between shed snake skin and human skin. Moreover, the permeability of compounds through shed snake skin was increased by Azone, one of the most extensively studied transdermal penetration enhancers. Considering the similarities between shed snake skin and human skin, ease of storage and handling, and low cost, shed snake skin may offer a good model membrane for transdermal research.

Animals↗
PubMed1990

Stereoselective hydrolysis of O-acetyl propranolol as prodrug in human serum.

A direct high-performance liquid chromatographic method was developed for the assays of the enantiomers of O-acetyl propranolol. Using this procedure, the stereochemical characteristics on hydrolysis of racemic O-acetyl propranolol as a prodrug have been studied in phosphate buffer (pH 7.4) and in 90% human serum. In the phosphate buffer, no difference in the hydrolysis rate between the esters of (R)- and (S)-propranolol was observed. In 90% human serum, the hydrolysis of the esters was accelerated, and the hydrolysis rate of the ester of (R)-isomer was about three times faster than that of the ester of (S)-isomer. The interconversion between (R)- and (S)-isomer was not observed during the hydrolysis of prodrug in buffer and in human serum. These results indicated that hydrolysis of O-acetyl propranolol occurs stereoselectively in human serum.

Chromatography, High Pressure Liquid↗
PubMed1989

New alkyl N,N-dialkyl-substituted amino acetates as transdermal penetration enhancers.

New alcohol derivatives of N,N-disubstituted amino acids with a low toxicity have been synthesized and evaluated for their transdermal penetration enhancing effects on the transport of indomethacin from petrolatum ointments across shed skin of black rat snake (Elaphe obsoleta). The derivatives show excellent penetration enhancement of indomethacin, as high as 3.8 times that of Azone, with decyl N,N-dimethylamino acetate as the lead compound in the series. The release of indomethacin from an ointment containing 1% indomethacin, 5% dodecyl N,N-dimethylamino acetate, and 94% petrolatum was 3.15 micrograms/min1/2/cm2. Saturation studies performed by incorporating varying concentrations of indomethacin, from 0.1 to 10%, into the ointments and determination of the fluxes of indomethacin demonstrated that the saturated concentration of indomethacin in petrolatum base was approximately 1%. Penetration fluxes of indomethacin (1%) through snake skin increased linearly as the concentration of dodecyl N,N-dimethylamino acetate increased from 2.5 to 15%. Experiments involving the pretreatment of the snake skins with dodecyl N,N-dimethylamino acetate indicated that pretreatment of the skin increased the skin permeability significantly. Electron micrograph studies on the snake skin treated with dodecyl N,N-dimethylamino acetate show clearly that the enhancer interacted with both the lipid-rich layer (mesos phase) and the keratin-rich layers (both alpha and beta phases).

Alkanes↗