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Biomedical subjects

S S Davis

Publications and source records attributed to S S Davis.

At least 181 records · Page 10Linked to original sources
PubMed1988

The stability and solubility of progabide and its related metabolic derivatives.

The stability-pH profile of the gamma-aminobutyric acid prodrug. Progabide, was found to be bell shaped, with maximum stability occurring at pH 6 to 7 with a t1/2 of 126 min. Of its metabolic derivatives, the deamidated product PGA degraded in a similar fashion to Progabide, whereas the hydrolytic degradation product SL79.182 was, a expected, a stable compound. Progabide behaved as a typical weak base, with its solubility increasing with a decrease in pH. SL79.182 behaved as a typical phenolic weak acid, with its solubility increasing with an increase in pH. Both compounds displayed low intrinsic solubilities of 14.5 x 10(-5) M for Progabide and 33.4 x 10(-6) M for SL79.182. An increase in temperature resulted in an increase in the solubility but a decrease in the stability of Progabide. The data obtained indicate that the gastric pH and gastric emptying rate will have a profound effect on the oral bioavailability of Progabide.

Anticonvulsants↗
PubMed1988

Relationship between the rate of appearance of oxprenolol in the systemic circulation and the location of an oxprenolol Oros 16/260 drug delivery system within the gastrointestinal tract as determined by scintigraphy.

1. The position in the gastrointestinal tract of an orally administered oxprenolol Oros drug delivery system labelled with technetium-99m DTPA was followed by gamma scintigraphy, and the corresponding plasma drug concentration-time profiles after oral and i.v. administration were used to relate pharmacokinetic and transit data. 2. Gastric emptying time (0.8 +/- 0.4 h, mean +/- s.d.), and the time to arrival in the colon (3.8 +/- 0.7 h) were reasonably consistent after administration of the Oros system to fasted subjects, as were the calculated small intestine transit times (3.0 +/- 0.7 h). As expected there were wide individual variations in colonic transit, so that recorded values for total transit ranged from 6 to 32 h (median, 24.7 h). 3. Absorption of oxprenolol occurred throughout the GI tract including the colon. Plasma drug concentration-time profiles and input functions (calculated by deconvolution) could be related to transit behaviour and in vitro release. Inflexions in the calculated rate of drug input when the Oros system was located in the colon corresponded with periods of stagnation at the hepatic and splenic flexures in two subjects and the ileocaecal junction in two others. The mechanism of these changes is unclear.

Adolescent↗
PubMed1988

Impotence and aging: clinical and hormonal factors.

A cross-sectional study of 216 impotent men aged 40 to 79 years (mean age 60.9 years) was conducted to determine if there are age-related changes in clinical and hormonal parameters in an impotent population. There was a slight increase in the degree of sexual dysfunction with age, with complete erectile failure occurring in a larger percent of the 60- and 70-year-olds than in the younger patients (41% vs 27% for the 40 year olds, P less than .05). No patient above the age of 70 years reported any full erections, even of short duration. In contrast, reported levels of libido did not vary significantly with age. Abnormal penile Doppler studies diagnostic of vasculogenic impotence were found in 17.8% of the patients tested, and an additional 17.8% were found to have evidence suggestive of a vascular etiology. These abnormal vascular findings were associated with an extremely high prevalence of clinically apparent atherosclerosis in this population. In 22.9% of the subjects, an abnormal vascular response was found only on exercise, ie, a "pelvic steal", which only occurred above the age of 50 years. There was a marked age-related alteration in the concentration of testosterone (T) and bioavailable testosterone (BT), but no statistically significant change in the levels of gonadotropins with age. An increase in the prevalence of eugonadotropic hypogonadism with age was found, which suggested an increasing prevalence of hypothalamic pituitary dysfunction in this patient group. For both vascular and hormonal changes (such as low T and BT), the greatest changes appear to occur after the age of 50.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Gastric emptying of large single unit dosage forms.

The gastrointestinal transit of two single unit dosage forms has been followed in healthy subjects under different feeding conditions. Transit was affected by the size of the meal administered. When two tablets were given concurrently they often emptied from the stomach at or about the same time, but in a number of cases the two units were seen to empty at widely different times.

Adolescent↗
PubMed1988

Toxicity of solubilized and colloidal amphotericin B formulations to human erythrocytes.

The toxicity of a number of solubilized or colloidal amphotericin B formulations to human erythrocytes has been studied in-vitro. All the solubilized formulations studied, using poloxamer F127 or L92, or sodium deoxycholate as solubilizing agents, showed similar toxicity, erythrocyte lysis being greater than 90% for amphotericin B concentrations between 4 to 8 micrograms mL-1. Emulsion formulations stabilized by poloxamers showed reduced toxicity, while those stabilized by egg lecithin showed less than 5% erythrocyte lysis up to an amphotericin B concentration of 200 micrograms mL-1. The mechanisms of the differential toxicity is considered to be due to the differences in the equilibrium concentration of free amphotericin B in the aqueous phase.

Adult↗
PubMed1988

Novel compositions of emulsified perfluorochemicals for biological uses.

Physico-chemical characteristics of novel perfluorodecalin emulsions stabilized against Ostwald ripening by the addition of polycyclic, perfluorinated oil additives are described. The effects of varying both oil additive and emulsifier concentrations have been examined. Stabilizing effects of additives were found to be related to molecular weight and hence, boiling point and vapour pressure.

Blood Substitutes↗
PubMed1988

Biocompatibility studies with a novel perfluorochemical emulsion.

Biocompatibility studies with a novel perfluorochemical (PFC) emulsion have been performed in rats. Injection of the emulsion was followed by changes in lymphoid tissue weights, comparable but not identical to those produced by the commercial formulation, Fluosol-DA 20% (F-DA). Peritoneal injection of either the novel emulsion or F-DA enhanced the humoral immune response to intraperitoneally-injected sheep red blood cells (SRBC) suggesting immunopotentiating properties of emulsion components.

Animals↗
PubMed1988

Intestinal absorption of proteins and macromolecules and the immunological response.

Progress in the field of biotechnology has renewed interest in the oral delivery of macromolecules, in particular, proteins and peptides. While small quantities of proteins may be absorbed from the gastrointestinal tract intact, enzymatic degradation and poor absorption have historically limited protein administration to the parenteral route. By consideration of the mechanisms of macromolecular absorption from the gut, it may be possible to exploit physiological processes to promote protein uptake. However, the response of the immune system to intestinally absorbed antigen may limit the oral delivery of proteins but could provide an attractive alternative to parenteral immunization.

Administration, Oral↗
PubMed1987

Targeting of colloidal particles to the bone marrow.

Since intravenously administered colloidal particles are normally removed efficiently by the reticuloendothelial cells of the liver and spleen only a small fraction of these particles will reach the bone marrow. By coating model microspheres with a block co-polymer (poloxamer 407) it has been possible effectively to hinder the liver/spleen uptake and obtain a deposition of the microspheres primarily in the bone marrow. Such a carrier system will have application in radiodiagnosis and for treatment of various diseases in the bone marrow.

Animals↗
PubMed1987

The organ distribution and circulation time of intravenously injected colloidal carriers sterically stabilized with a block copolymer--poloxamine 908.

Colloidal carriers injected intravenously are normally removed rapidly and efficiently by the liver and this represents a major barrier to drug targeting. By coating model microspheres and emulsions with a block co-polymer (poloxamine) it has been possible to keep the carrier circulating in the vascular compartment with little or no uptake by the reticuloendothelial system.

Animals↗
PubMed1987

Androgen therapy of hypogonadal men with transscrotal testosterone systems.

The need for improved controlled delivery of testosterone to hypogonadal men stimulated the development of a self-adherent transscrotal testosterone system to provide programmed testosterone delivery through the uniquely permeable scrotal skin. In this short- and long-term efficacy trial, the responses of testosterone and its metabolites to the application of transscrotal testosterone systems of varying testosterone content were compared with the response to 200 mg of testosterone enanthate. Daily transscrotal testosterone system administration resulted in a rapid increase of testosterone and bioavailable, non-sex hormone binding globulin-bound testosterone levels to normal, peaking at two hours, followed by a slow decline over 23 hours, resembling the diurnal variation of endogenous testosterone. One year of daily transscrotal testosterone system therapy demonstrated continued reliable absorption of testosterone and suppression to normal of the luteinizing hormone in two of three patients. There was a greatly disproportionate increase of serum dihydrotestosterone over testosterone, suggesting 5-alpha reduction at the scrotal site. The subjects reported marked subjective improvement. Thus, the transscrotal testosterone system is a novel, effective, and well-tolerated method of delivering testosterone to hypogonadal patients.

Administration, Cutaneous↗
PubMed1987

Surface characteristics and the interaction of colloidal particles with mouse peritoneal macrophages.

The effect of surface characteristics on the interaction of sterically stabilized polystyrene particles with mouse peritoneal macrophages was studied using a range of poloxamers and poloxamine as coating agents. The coated particles were characterized in terms of thickness of coating layer, surface charge and critical flocculation temperature. The relative phagocytic uptake was found to decrease with increasing adsorbed layer thickness i.e. longer hydrophilic polymer chains of the coating agent and consequently a greater steric stabilization effect.

Animals↗
PubMed1987

A reversed-phase high-performance liquid chromatography assay procedure for progabide and its related metabolic derivatives.

A reversed-phase high-performance liquid chromatography (HPLC) assay procedure for Progabide, its active acid metabolite (PGA), and its hydrolytic degradation product (SL79.182) has been developed. This highly specific technique has allowed the simultaneous determination of these drugs in aqueous samples, and when coupled with a single and easy extraction step, spiked plasma samples could also be analyzed. The method had a sensitivity of about 30, 45, and 100 ng/ml for Progabide, SL79.182, and PGA, respectively.

Calibration↗
PubMed1987

Investigation of the gastrointestinal transit and in vivo drug release of isosorbide-5-nitrate pellets.

An oral formulation of controlled-release isosorbide-5-nitrate pellets has been used to investigate the location of pellets in the gastrointestinal (GI) tract and, in parallel, to measure the drug absorption from these locations. Using the method of gamma scintigraphy the transit times and spreading of pellets in the GI tract have been determined. The method of numeric deconvolution was applied to calculate the drug input into the systemic circulation. The results indicate that a well-absorbed substance such as isosorbide-5-nitrate is absorbed from the stomach and small intestinal in a manner that is controlled by the properties of the pellets. Drug absorption is reduced in the colon. The average transit time from mouth to colon is 6 to 8 hr, which represents the maximum acceptable time for drug release for this oral controlled-release preparation. Taking into account these relations an isosorbide-5-nitrate pellet formulation with a bioavailability of 84% has been developed that maintained the minimal therapeutic plasma level for more than 16 hr after application.

Delayed-Action Preparations↗