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Biomedical subjects

E T Sugita

Publications and source records attributed to E T Sugita.

At least 19 recordsLinked to original sources
PubMed1996

Theophylline controlled-release formulations: in vivo-in vitro correlations.

Four experimental controlled-release oral solid dosage formulations were developed and the in vitro dissolution characteristics of theophylline from these formulations were studied in USP apparatus I. Pharmacokinetic evaluation of these formulations was carried out in eight beagle dogs under fasting conditions. Theophylline in a 5% dextrose injection USP, oral solution, and Slo-Phyllin were used as controls to estimate the in vivo dissolution of these four formulations in the GI tract. The percentage cumulative amounts of drug absorbed and the percentage cumulative amounts of drug released into the GI tract from these four controlled-release formulations were obtained by numerical deconvolution methods. The in vivo and in vitro dissolution data demonstrated good correlation indicating that in vitro dissolution tests can be used to optimize the further design of controlled drug release oral solid dosage formulations for theophylline.

Animals↗
PubMed1996

Five modified numerical deconvolution methods for biopharmaceutics and pharmacokinetics studies.

Four improved finite-difference numerical deconvolution methods and one nonlinear regression numerical deconvolution method are proposed and implemented using IMSL/IDLTM. These five numerical deconvolution methods are evaluated using simulated data generated with and without added noise under six different dosing cases. Comparisons between these methods are made in terms of the superimposability of the calculated cumulative amount of drug released or absorbed-time profiles with the theoretical data. The results indicate that the proposed fixed step number equal step length numerical deconvolution method is simple and accurate and therefore is appropriate for pharmacokinetic and biopharmaceutic studies. When an analytic function is legitimate to represent the drug input rate, the nonlinear regression numerical deconvolution method will yield enhanced numerical accuracy and stability.

Absorption↗
PubMed1993

Determination of polyanionic macromolecules by size-exclusion chromatography.

This report presents an extension of a method developed for determination of dextran sulfate in rat serum. The drug is a negatively charged polysaccharide with a molecular mass of 8000. It is fractionated by molecular size and separated from serum components by high-performance size-exclusion chromatography. Sensitive detection is achieved by the post-column complexation of the analyte with 1,9-dimethylmethylene blue (DMMB). A metachromatic complex is formed; the absorbance maximum of the complex is shifted from that of the free dye. Various glycosaminoglycans and other macromolecular polyanions interact with DMMB. Several can be determined using the chromatographic conditions developed for dextran sulfate. The method provides a simple procedure for quantitation of these compounds. Compared to spectrophotometric assays, less sample preparation is required, selectivity is enhanced, and molecular mass information is provided. With modification of eluent composition, dye concentration, and detection wavelength, the method can be validated for determination of additional compounds.

Animals↗
PubMed1993

Size-exclusion chromatographic determination of dextran sulfate in rat serum.

A sensitive and selective method for the determination of dextran sulfate in rat serum has been developed. The analysis is suitable for quantitation of the drug and for monitoring molecular mass changes occurring during biotransformation. Dextran sulfate is resolved from higher molecular mass serum components by high-performance aqueous size-exclusion chromatography. The method has been validated for the direct injection of serum. Sensitive detection is achieved by post-column reaction of the polyanionic drug with the dye 1,9-dimethylmethylene blue. Components of serum which inhibit complex formation are separated chromatographically from dextran sulfate. Absorbance of the metachromatic complex is monitored at 525 nm.

Animals↗
PubMed1992

Effect of surfactant phase in perfluorocarbon emulsification efficiency.

The effect of preparation temperature on the emulsification efficiency of perfluoro-3-butyltetrahydrofuran (FC-75) was investigated. Polyoxyethylene (POE) oleyl ether surfactants were used as the emulsifier(s) in a range of HLB values of 7.5 to 9.5. The emulsions were prepared by paddle mixing as a method of low-shear emulsification. After centrifugation of the resulting O/W emulsions, the volume of FC-75 which separated was utilized as a measure of the emulsification efficiency. In general, emulsions prepared at temperatures where the surfactant was in a lamellar-to-isotropic surfactant solution transition, L alpha----L3, displayed a better emulsification efficiency than those prepared with other surfactant phases.

Drug Stability↗
PubMed1991

The relationship of salicylate lipophilicity to rectal insulin absorption enhancement and relative lymphatic uptake.

The sodium salts of the 3,5-dichloro, 3,5-dibromo-, 3,5-diiodo-, and 5-methoxy- analogs of salicylic acid have been evaluated as enhancers of rectal insulin absorption. A relationship was found between adjuvant potency and relative lipophilicity. Maximal adjuvant activity was obtained with 0.1 M 3,5-dichlorosalicylate. Higher concentrations (0.15 M) of 3,5-diiodosalicylate produced a decline in adjuvant activity, which may be associated with extraction of specific cellular proteins. This may indicate the existence of an optimal salicylate lipophilicity for adjuvant efficacy. Relative adjuvant activity was found to be related to the lymph:plasma absorption ratio of [125I]insulin. Lymphatic uptake of insulin was not related to lymph flow rate.

Animals↗
PubMed1988

Predicting coordinated lipid biosynthesis: application to the surfactant-accommodated epidermis.

Factorialized correlation analysis is proposed as a method for predicting the coordination of multiple enzyme pathways. The approach can be used potentially to find new relationships and to predict relationships that have been established in other tissues. However, careful tracer studies are needed to verify the cause-and-effect relationships between precursor and products. In this study, guinea pigs that were chronically treated with an anionic, a nonionic and a cationic surfactant passed through an irritation stage to a clinical state that appeared normal. The method was used to examine binary coordination of lipid biosynthesis in the epidermis by using a factorialized table of regression coefficients. Coordinated lipid relationships that have been reported in other tissues were predicted between sphingomyelin and cholesterol, as well as between phosphatidylcholine, phosphatidylserine and phosphatidylethanolamine. A new inverse relationship was found between triglycerides and both sphingomyelin and cholesterol, using this method. These data are discussed with respect to a membrane fluidization model for the accommodated state.

Animals↗
PubMed1986

The pharmacodynamic response of the basal skin potential to quinidine gluconate.

The basal skin potential (BSP) was explored as an indirect means of continuously monitoring the cardiac response of quinidine gluconate. A method was developed to follow the BSP using a high impedance, recording polygraph and nonpolarizing calomel electrodes. Intravenous administration of quinidine gluconate caused time dependent changes in the BSP. Further studies showed that blood levels during the elimination phase and the QT interval of the electrocardiogram (ECG) over their entire time period were highly correlated with the BSP. Optimal correlation with the QT interval occurred when the BSP curve was shifted to earlier times by approximately 10 minutes, reflecting possible differences in the accessibility or mechanism of the respective pharmacologic compartments. Further application of the BSP for pharmacodynamic monitoring will require electrode refinements and an increased understanding of its mechanism of action.

Animals↗
PubMed1984

Percutaneous absorption: a new physicochemical predictive model for maximum human in vivo penetration rates.

A diffusion model for stratum corneum-limited percutaneous absorption based on the interaction of the diffusate with the stratum corneum was derived. Two types of interactions were proposed, ion-dipole and lipid-lipid, based on current knowledge of the stratum corneum and on irreversible thermodynamic arguments. The resulting flux equations predict a linear dependence of flux on the dipole moment and ln X of the diffusates , where X is the mole fraction solubility. These flux equations were tested on 21 different diffusates whose human percutaneous absorption rates in vivo had been previously determined. A solubility method was used to classify the interaction pathway for each diffusate . Correlation of the maximum absorption rate for the lipid and polar pathways give correlation coefficients of 0.946 and 0.998, respectively. It is believed that these studies provide a starting point for the ultimate goal of percutaneous absorption research: to be able to bypass in vivo and in vitro studies and to predict absorption solely on the basis of the physicochemical properties of the diffusates .

Chemical Phenomena↗
PubMed1982

Guinea pig ear as a new model for in vivo percutaneous absorption.

A new animal model for in vivo percutaneous absorption utilizing the hairless, relatively thick skin of the guinea pig ear is proposed. Topical absorption studies were carried out with [14C]hydrocortisone and [14C]testosterone. Systemic studies were also conducted to correct for incomplete urinary excretion. In addition, a single stratum corneum correction factor was developed from published data to enable the guinea pig ear skin to be directly compared with human forearm skin. A comparison of human percutaneous absorption with the corrected guinea pig ear absorption shows a high correlation for both hydrocortisone and testosterone. The effects of ambient changes in relative humidity are also discussed with respect to in vivo percutaneous absorption.

Administration, Topical↗
PubMed1980

Influence of various anions on intestinal disappearance of hexamethonium chloride and pralidoxime chloride in rats.

The intestinal transfer of two poorly absorbed quaternary ammonium drugs, hexamethonium chloride (I) and pralidoxime chloride (II), in the presence of various organic and inorganic anions was investigated in the rat using a modified in situ gut technique. The results were in agreement with those of the conventional in situ loop and plasms drug level techniques. Of the anions investigated, cholate, desoxycholate, taurocholate, phoscholate, dehydrocholate, and hyodesoxycholate had the greatest effect on increasing the amount and rate of disappearance of I. Similarly, the amount and rate of disappearance of II were enhanced markedly in the presence of phoscholate and trichloroacetate. The effect of cholate and phoscholate was investigated in detail. The membrane permeability and histological studies indicated that these anions may compromise the structural integrity of the membrane tissue, thus enhancing drug transfer.

Animals↗
PubMed1979

Kinetics of absorption and elimination of pralidoxime chloride in dogs.

The kinetics of the absorption and elimination of pralidoxime chloride were investigated in the dog. Similar apparent elimination rate constants were obtained after intravenous, intramuscular, and oral administration. Although oral absorption occurred slowly, intramuscular absorption proceeded rapidly. With in situ techniques, it was found that no absorption occurred from the isolated stomach and duodenum but that absorption did take place from the jejunum and ileum.

Absorption↗
PubMed1977

Kinetics of intravenous theophylline.

The pharmacokinetics of theophylline was studied in 6 normal, nonsmoking, adult male volunteers. A constant-rate intravenous infusion of 3.84 to 4.98 mg/kg of theophylline (as the ethylenediamine salt, aminophylline) was administered over 40 min. Serum theophylline concentrations were measured for 24 hr by means of a gas chromatographic method specific for theophylline. Within 30 min of an average intravenous dose of 4.4 mg/kg of theophylline, serum levels reached 10 microgram/ml. The highest serum level at the end of the infusion was 17 microgram/ml. The serum concentration-time data were fitted to a two-compartment open model and yielded a mean serum half-life (t1/2) of 11.02 hr, a value longer than those previously reported. Our results indicated that after the original loading dose of 4.4 mg/kg was infused for 40min, an immediate infusion rate of 1.40 mg/kg/hr (1.65 mg/kg/hr aminophylline) would be necessary to maintain a serum level of 10 microgram/ml.

Adult↗
PubMed1977

Determination of theophylline and its metabolites by liquid chromatography.

A high pressure liquid chromatographic assay has been developed for the separation and quantitation of theophylline and its metabolites (1-methyl uric acid, 3-methyl xanthine, and 1,3-dimethyl uric acid), theobromine, and dyphylline in biological fluids, viz. human serum, urine, and saliva. The serum has been rendered protein-free by passage through a filter with a nominal molecular weight limit of 10,000. The filtrate is injected onto a reverse-phase column and the separation achieved by utilizing a polar mobile phase and dyphylline (dihydroxypropyl theophylline) as the internal standard. The results for two normal subjects are included to illustrate the applicability of the technique.

Chromatography, High Pressure Liquid↗
PubMed1975

Rapid methods for bioavailability determination utilizing urinary excretion data.

Two equations were developed which enable urinary excretion data to be utilized for estimating drug bioavailability within 12 hr-starting between one and two half-lives of the drug, depending upon the relative rates of absorption, distribution, and elimination. Both equations were examined using simulated data for both the one- and two-compartment open models. One equation was tested using literature data with excellent results.

Absorption↗