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Biomedical subjects

K Sugibayashi

Publications and source records attributed to K Sugibayashi.

At least 19 recordsLinked to original sources
PubMed1994

The effect of different routes of administration on the metabolism of morphine: the disposition of morphine and its metabolites after topical application.

The disposition of morphine (MOR) and its metabolites in the rabbit was measured after topical administration of its hydrochloride salt (MOR.HCl), and their time course was compared with those after intravenous and oral administration. The area under the plasma concentration-time curve (AUC) ratio of metabolites/MOR after the topical application of MOR.HCl was similar to that after intravenous injection, but differed from that after oral administration. Pharmacokinetic parameters of the disposition of MOR and its metabolites were obtained by a general curve fitting of the time course of plasma concentrations of these compounds after intravenous injection of MOR.HCl and its metabolites, respectively. On the other hand, the time courses of plasma concentrations of the metabolites after intravenous, oral, and topical administration of MOR.HCl were simulated using a simple compartment model without consideration of enterohepatic circulation and the pharmacokinetic parameters obtained as above. The resulting curves of the metabolites agreed well with the observed values except for those after oral administration. These results suggest that no first-pass metabolism of MOR.HCl occurs after percutaneous administration, and that topical administration of this salt is more advantageous than oral administration in terms of bioavailability.

Administration, Oral↗
PubMed1994

Interaction between drugs and pressure-sensitive adhesives in transdermal therapeutic systems.

Release experiments with four drugs using representative pressure-sensitive adhesive (PSA) matrices were performed at 37 degrees C, and drug-PSA polymer interaction was determined by the Williams, Landel, and Ferry (WLF) equation. Two acrylic-type [2-ethylhexylacrylate and acrylic acid copolymer (2EHA/AA) or acrylamide copolymer (2EHA/AAm)], one rubber-type (a mixture of high and low molecular weight polyisobutylene), and one silicone-type PSA were used, and dipropylphthalate (PP), aminopyrine (AMP), ketoprofen (KP), and lidocaine (LC) were selected as model drugs because of their molecular size and functional groups. PSA containing acrylic acid (2EHA/AA) strongly interacted with the amide LC, with the tertiary amine AMP, and with the carboxylic acid KP; PSA-containing acrylamide (2EHA/AAm), however, did not interact with LC or AMP, although it markedly interacted with KP. The rubber-type and silicone-type PSAs, composed of no or only a few polar functional groups, did not interact with any of the drugs used in this experiment. Therefore, the diffusion coefficient of the drugs through PSA was influenced by the drug-PSA polymer interaction, and the extent of this interaction can be estimated by the relationship between the drug concentrations in the PSA and their diffusion coefficients.

Acrylates↗
PubMed1994

An application of the hydrodynamic pore theory to percutaneous absorption of drugs.

Skin permeability of drugs was evaluated based on the hydrodynamic pore theory. Four polar solutes were used, with differing molecular sizes--ethylene glycol, 1,3-butylene glycol, antipyrine and sucrose--and isosorbide dinitrate was also selected as a lipophilic drug. The skin permeations of solvent (D2O) and one of these drugs were measured simultaneously under various osmotic pressures to calculate the reflection coefficient. The clearance of isosorbide dinitrate was independent of the solvent flux, whereas a linear relationship was obtained between the solvent flux and the clearance of each hydrophilic drug except for sucrose. The reflection coefficient of the hydrophilic drugs increased with increasing molecular radius. These results suggest that the convective flow contributes significantly to the total skin permeability of hydrophilic drugs and that the extent of contribution decreases with increasing molecular size of the drugs. The pore radius of the skin barrier could be estimated from the reflection coefficient of the hydrophilic drugs and the resulting value was compared with that for the other absorption sites, jejunum, rectum, and nose. The apparent water influx was also compared to assess the volume occupied by the pores. The pore radius and apparent influx of skin were lower than those for the other absorption sites, which is apparently one reason for low skin permeability of drugs, especially hydrophilic drugs.

Animals↗
PubMed1994

Analysis of the combined effect of 1-menthol and ethanol as skin permeation enhancers based on a two-layer skin model.

The combined effects of 1-menthol and ethanol as a skin permeation enhancer were evaluated with two equations describing the permeability coefficient through full-thickness skin (PFT) and the full-thickness skin/vehicle concentration ratio (CFT/CV) of drugs as a function of their octanol/vehicle partition coefficient (KOV). A two-layer model was applied for skin, which consists of a stratum corneum (SC) with lipid and porous pathways and a viable epidermis and dermis (ED). The two equations contain one variable (KOV) and nine coefficients, six of which (three diffusion coefficients, the porosity of the SC, and two terms of the linear free energy relationship) were considered different, dependent on the drug vehicle. In vitro permeation of four drugs (morphine hydrochloride, atenolol, nifedipine, and vinpocetine) was determined using excised hairless rat skin and four aqueous vehicles (water, 5% 1-menthol, 40% ethanol, and 5% 1-menthol-40% ethanol) to measure each PFT. Drug concentrations in full-thickness skin were also measured to obtain CFT/CV. A nonlinear least-squares method was employed to determine six coefficients using the two equations and experimentally obtained PFT and CFT/CV. The addition of 1-menthol to water and 40% ethanol increased the diffusion coefficient of drugs in lipid and pore pathways of SC, whereas the addition of ethanol to water and 5% 1-menthol increased the drug solubility in the vehicle, decreased the skin polarity, and increased the contribution of the pore pathway to whole-skin permeation.

Animals↗
PubMed1994

Effect of skin surface lipid on the skin permeation of lidocaine from pressure sensitive adhesives.

Pressure sensitive adhesives (PSA) tapes containing different concentrations of lidocaine were prepared by a general casting method using styrene-isoprene-styrene block copolymer, and the in vitro skin permeation of lidocaine from each tape was evaluated using diffusion cell and excised hairless rat skin. The skin permeation was proportionally increased by up to 40% lidocaine in the PSA tape and did not change after this concentration. Although the bending point of the steady-state flux via skin concentration curve was found at 40%, saturated concentration or solubility of lidocaine in the tape was estimated to be about 20% by differential scanning calorimetry (DSC) measurement. In addition, the steady-state flux of lidocaine through skin from water or silicone fluid suspension (92 or 120 micrograms/cm2.h, respectively) was very similar to those of 40, 50 and 60% tapes (105, 101 and 112 micrograms/cm2.h, respectively). Decrease in the concentration in tapes during the permeation experiment explained only part of these phenomena. To analyze them further, the drug free PSA tape with or without (control) skin surface lipid was affixed to 50% lidocaine PSA tape for 48 h, and the amount of lidocaine crystal in the layered tapes was measured by DSC. The amount was found to be lower in the lipid-containing tape than in the lipid-free tape, suggesting that skin surface lipid can dissolve lidocaine crystal or solid in PSA tape to decrease its thermodynamic activity. Thus it is important to follow the concentration and thermodynamic activity of lidocaine in PSA tape, skin and the interface between the two layers to exactly assess its skin permeation flux.

Adhesives↗
PubMed1994

Evaluation of enhancers to increase nasal absorption using Ussing chamber technique.

The effects of eight prospective absorption enhancers on the nasal mucosa in rabbit have been assessed using an in vitro Ussing chamber technique. Sodium taurodihydrofusidate (STDHF), sodium deoxycholate (DC), polyoxyethylene-9-lauryl ether (BL-9), lysophosphatidylcholine (LPC) and sodium dodecyl sulfate (SDS) were found to possess relatively high protein leaching activity, while sodium glycocholate (GC), sodium taurocholate (TC) and EDTA had relatively low activity. The permeation of fluorescein isothiocyanate-labeled dextran (FD, M.W. 9400) as a model drug across the nasal mucosa was found to be greater in the presence of these enhancers. Their enhancement ratio was found to be in the order of BL-9 > STDHF > SDS > LPC > DC > EDTA > GC > TC, which correlated with the protein leaching activity. The differences in protein leaching and enhancement ratio dependent on the magnitude of change of membrane resistance (delta Rm), indicating that these enhancers damaged the membrane and increased FD permeation. delta Rm thus appears to be a useful indicator by which one can estimate nasal mucosa damage by the enhancers.

Absorption↗
PubMed1994

In vitro-in vivo correlation of percutaneous absorption: isosorbide dinitrate and morphine hydrochloride.

The potential of an in vitro skin preparation as a model for predicting in vivo percutaneous absorption of drugs was examined. In vitro and in vivo skin permeation data for two model drugs with different lipophilicity, isosorbide dinitrate (ISDN) and morphine hydrochloride (MPH), were compared using pharmacokinetic techniques. In vitro permeation data published previously were analyzed based on a single pathway model, and permeation parameters were obtained. The disposition parameters were estimated from the plasma concentration profiles after i.v. administration. The plasma concentrations after topical application were then simulated using the obtained permeation and disposition parameters, and the values were compared with the corresponding observed ones. Although the simulated plasma concentration curves were not greatly different from those observed, there were some differences in the time course-pattern. Causes for these in vitro-in vivo differences were discussed.

Animals↗
PubMed1993

The structural barrier of absorptive mucosae: site difference of the permeability of fluorescein isothiocyanate-labelled dextran in rabbits.

The permeability of fluorescein isothiocyanate-labelled dextran (FD, M.W. 4400-71,200) across nasal, buccal, duodenal, jejunal, ileal, colonic, and rectal mucosae excised from rabbits has been measured to estimate the structural barrier of absorptive mucosae using Ussing-type diffusion chambers. The permeability coefficient of FD in all these mucosae decreased with increasing molecular weight. The rank order of FD permeability did not always correlate with the electrical resistance of the mucosae. Among components of the small intestine (duodenum, jejunum, ileum) and the large intestine (colon, rectum), however, the rank order of FD permeability corresponded to the magnitude of the electrical resistance in each instance; the upper colonic mucosa showed the highest permeability, especially in FD of low molecular weight, and permeability of the rectal mucosa was lowest except for the duodenal mucosa. The nasal mucosa showed the lowest electrical resistance and the highest permeability of those studied, suggesting that it has a leaky structural barrier.

Animals↗
PubMed1993

Non-invasive sampling of lactic acid ions by iontophoresis using chloride ion in the body as an internal standard.

Non-invasive sampling of lactic acid, as a model endogenous compound, through hairless rat skin by iontophoresis was investigated using a two-chamber iontophoretic diffusion cell equipped with platinum electrodes and a pulse depolarization iontophoretic system. Chloride ion in the body was used as an internal standard. First, an in vitro experiment on the permeation of lactate and chloride ions through hairless rat skin was carried out to determine the flux ratio of these ions. The cathode side of the cell (dermis side) was filled with physiological saline containing lactic acid (0.5556, 1.111, 1.667 or 2.222 mmol cm-3) and the anode side (epidermis side) with phosphate buffer (pH 7.4). The amount of lactate and chloride ion permeated from the dermis side to the epidermis side through the skin at a constant current of 3.0 mA was determined using an automatic lactic acid analyser and high-performance ion chromatography, respectively. For construction of a calibration curve of lactic acid in the dermis side, the ionic mobility ratio of lactic acid/chloride ion (UCl/Ulac) was determined using a computer simulation program from the flux ratio of lactic acid and chloride ion and the applied concentration of lactic acid in the dermis side. Second, an in vitro non-invasive sampling experiment of lactic acid through rat skin was carried out at a constant current of 2.0 or 3.0 mA and 2.222 or 1.111 mmol cm-3 of lactic acid in the dermis side, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Comparison of depolarizing and direct current systems on iontophoretic enhancement of transport of sodium benzoate through human and hairless rat skin.

A direct current (DC) system and a pulsed depolarization (PD) system were evaluated for their iontophoretic permeation of sodium benzoate, as a model drug, through hairless rat and human skin. Approximately the same initial permeation of sodium benzoate through the hairless rat skin was obtained at 0.1 mA for the DC device and at 3.0 mA for the PD device. Study of the drug's permeation was performed using a two-chamber iontophoretic diffusion cell, over two cycles of three successive on-off experimental conditions [stage I (off) 0-4 h, II (on) 4-6 h, III (off) 6-10 h, saline washing 10-24 h, IV (off) 24-28 h, V (on) 28-30 h and VI (off) 30-34 h]. Skin permeation rate during stage IV of the iontophoresis as compared with the control group through hairless rat or human skin for the DC system was 2-4 times that in stage I, whereas in the same stage using the PD system it was almost the same as in stage I. Impedance of skin decreased during the application of either system (stage II); however, the value significantly recovered during stage III only in the case of the PD system use on human skin. Histological observation revealed no tissue alteration in the hairless rat skin after using either system. When the DC or PD system was applied to volunteers, the minimum current density producing pain was 0.016 or 2.7 mA cm-2, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Selective accumulation and tumoricidal effect of cisplatin suspended in viscous ethyl oleate on hepatic cancers in animals after intraarterial infusion.

The selective accumulation and tumoricidal effects of cisplatin after intra-arterial infusion suspended in viscous ethyl oleate (VEO) on hepatic cancers of AH 272 tumor-bearing rats and VX-2 tumor-bearing rabbits were compared with those of cisplatin suspensions in ethyl oleate (EO) and Lipiodol Ultra Fluide (LP). The viscosities of VEO, EO and LP were 120, 4, and 21 centipoise (cp) respectively. Complete in vitro release of cisplatin from EO and LP occurred within 24 h, whereas only about 25% of cisplatin was released from VEO over the same period. When EO or VEO containing 3H-oleic acid were infused into the hepatic artery of rat liver inoculated with AH 272 tumor cells, radioactivity in the tumor site was higher than that in normal liver. In the case of cisplatin, concentration ratios after the infusion of EO and VEO were almost the same as those of oily carriers. Similar results were obtained in rabbit liver inoculated with VX-2 tumor cells. Cisplatin concentration in the tumor site seven days after intra-arterial infusion of VEO suspension was 5- and 1.7-fold higher, respectively, than that after EO and LP suspensions. The tumoricidal effect of cisplatin in VEO suspension on AH 272 tumor-bearing rats was higher than that after cisplatin solution and EO and LP suspensions, while VX-2 tumor growth was inhibited by the infusion of all cisplatin-containing oily carriers. VEO suspension thus appears very promising in intra-arterial infusion therapy.

Animals↗
PubMed1992

Mechanism of skin penetration-enhancing effect by laurocapram.

In order to clarify the mechanism of action of laurocapram (Azone) on the skin permeation of drugs, the following experiments were done. First, the effect of Azone on the skin components was compared with that of other penetration enhancers. Azone markedly fluidized liposomal lipids (as a model lipid system) compared with other enhancers. Ethanol extracted large amounts of the stratum corneum lipids, whereas Azone did not. These results suggest that the effect of Azone on the lipids in the stratum corneum is not the same as that of ethanol. In addition, ethanol increased the amount of free sulfhydryl (SH) group of keratin in the stratum corneum, whereas Azone did not directly affect the stratum corneum protein. Azone increased water content in the stratum corneum, as measured by skin conductance. This effect might be a reason for the action of Azone. For further understanding, the enhancing effects of Azone on the skin permeation of several model compounds (alcohols, sugars, and inorganic ions) were compared with the effects of pretreatment with distilled water, which was thought to increase water-holding capacity, and pretreatment with ethanol, which was thought to affect the lipids and protein in the skin barrier (i.e., stratum corneum). Pretreatment with water or ethanol enhanced skin permeation of hydrophilic compounds, whereas they decreased that of octanol, a hydrophobic compound. The tendency of Azone to increase or decrease the skin permeation rate of most compounds was similar to that of pretreatment with water or ethanol. However, the effect of Azone on the skin permeation of inorganic ions was relatively low, whereas that of pretreatment with water or ethanol was high.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohols↗
PubMed1992

Prediction of skin permeability of drugs: comparison of human and hairless rat skin.

Relationships between skin permeability and physicochemical properties of drugs were examined to establish a predictive method for the steady-state permeation rate of drugs through human skin. Human skin permeation properties fell into two categories: one in which the permeability coefficient is correlated to the partition coefficient, revealed with lipophilic drugs; and the other in which the permeability coefficients are almost constant, shown with hydrophilic drugs. The stratum corneum, the main barrier in skin, could be considered as a membrane with two parallel permeation pathways: lipid and pore pathways, and an equation for predicting the steady-state permeation rate of drugs was derived. The skin permeabilities of drugs for man were compared with those for hairless rat. The species difference in skin permeability found was suggested to be due to the difference in skin permeation pathways, since lipid content and water uptake of the stratum corneum varied between human and hairless rat skin.

Animals↗
PubMed1992

Oily drug carriers in cancer chemotherapy. II. Preparation of viscous ethyl oleate for intraarterial infusion therapy and its disposition in rats and hamsters.

Viscous ethyl oleate (VEO) was prepared as an oil drug carrier by the addition of aluminum stearate or ethyl cellulose. Since the rate of shear of VEO containing aluminum stearate was greatly and nonlinearly changed against the shearing stress compared to that containing ethyl cellulose, the latter was used for subsequent microvascular and organ distribution experiments in rats and hamsters. For infusion into the carotid artery in hamsters, neat ethyl oleate (EO, 4cP) or VEOs of various apparent viscosities (40, 80, 120 cP-VEOs) embolized the vascular system in the cheek pouch, although arrival time to the site where the embolization was observed and the embolization period differed depending on the type of oily drug carrier. For infusion into the hepatic artery in rats, however, only 120 cP-VEO embolized the vascular system in the liver. After infusion of the oily drug carrier containing 3H-oleic acid into the artery of hamster cheek pouch and rat liver, 30-50% of the radioactivity was gradually eliminated within 48 h, whereas about 80% of the dose was rapidly eliminated after infusion to rat stomach and kidney. In addition, the amount of 120 cP-VEO remaining in each organ 48 h after infusion was higher than those of EO and 40 and 80 cP-VEOs. Histological observation after infusion in rat liver revealed that 120 cP-VEO slowly migrated from the artery or arteriole to the sinusoidal capillary region. These results suggest that 120 cP-VEO can be used as a drug carrier because of its function of vascular embolization and high retention in a targeted tissue.

Animals↗
PubMed1992

Calculation of skin permeability coefficient for ionized and unionized species of indomethacin.

The contribution of ionized and unionized species to the overall permeation of weak electrolytes through the skin was investigated to determine the effect of pH in the vehicle on the permeability of indomethacin (IDM), as a model drug, through hairless rat skin. The permeability of IDM through polydimethylsiloxane (silicone) and poly(2-hydroxyethyl methacrylate) (pHEMA) membranes which may reflect lipid and aqueous pathway, respectively, was also measured for comparison. As the pH in the vehicle increased, there was an exponential increase in the skin permeation rate of IDM. The permeation rate of IDM through the silicone membrane was constant independent of pH, whereas that through the pHEMA membrane increased with increasing pH, similar to the skin permeation. The permeability coefficients of ionized and unionized species through the skin estimated using the skin permeation rates and solubilities of IDM at various pHs were 1.50 x 10(-7) and 2.79 x 10(-5) cm/s, respectively. These results indicated that the permeation of ionized species greatly contributed to the total permeation of IDM at higher pH, and that the total permeation rate of IDM was determined by the permeation of unionized species at lower pH. These contributions depend on the pH and pKa values and the ratio of permeability coefficient of each species. It was also confirmed that the skin has at least two kinds of permeation pathways and these two species permeate through a different pathway.

Administration, Cutaneous↗
PubMed1991

Preparation of thermo-responsive polymer membranes. I.

Two types of liquid crystal (LC)-entrapped membranes, (a) polymer alloyed membranes and (b) LC-adsorbed membranes, were investigated for the purpose of developing the drug delivery systems (DDS) with thermal stimuli responsing. Polymer alloyed membranes were obtained by polymerizing acrylic monomers in presence of LC and LC-adsorbed membrane were obtained by adsorbing LC into porous hydrophobic polymer membrane. It was made clear from the indomethacin permeation experiments below and above the gel-liquid crystal phase transition temperature of the LC that the extent of thermo-sensitivity for LC-adsorbed membranes was greater than that for the alloyed membrane. The permeability ratio (38 degrees C vs. 32 degrees C) was found to be about 120 with the LC-adsorbed membrane. It was suggested from the results that the LC-adsorbed membrane was one of the useful candidates as a thermo-responsive system for DDS.

Biocompatible Materials↗
PubMed1991

Preparation of thermo-responsive membranes. II.

Two types of liquid crystal (LC)-immobilized membranes were prepared by a soaking method and sandwich method to control the permeation of indomethacin, as a model drug, in response to local and systemic fever. Monooxyethylene trimethylolpropane tristearate (MTTS) was used as a model LC because it has a gel-liquid crystal phase transition temperature near the body temperature, 39-40 degrees C in phosphate buffered saline (pH 7.4). Two porous polypropylene (PP) membranes were soaked into 20% MTTS chloroform solution in the soaking method, and two PP membranes were poured with the melted MTTS and pressed in the sandwich method. Thermo-response efficacy of the soaked membrane was dependent upon the content of MTTS in MTTS membrane, and the MTTS content above the void volume of PP membrane (38%) was needed for high efficacy. On the other hand, the sandwich membrane exhibited higher thermo-response efficacy than the soaked membrane, because more LC was embedded in the pores of sandwich membrane than that of the soaked membrane. The sandwich membrane permeation of indomethacin was sharply controlled by temperature changes between 32 and 38 degrees C.

Administration, Cutaneous↗