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Biomedical subjects

A Hurwitz

Publications and source records attributed to A Hurwitz.

At least 145 records · Page 8Linked to original sources

Effect of cimetidine and antacids on gastrointestinal absorption of tetracycline.

In a randomized crossover study, five normal subjects were given 250-mg capsules of tetracycline at weekly intervals with cimetidine 300 mg. sodium bicarbonate 2 gm in water, magnesium-aluminum hydroxide gel 30 ml, or water alone. Gastric pH was monitored by radiotelemetry. Antibiotic bioavailability as measured by area under the serum level-time curve, peak serum level, and urinary elimination was not affected by cimetidine or sodium bicarbonate. Magnesium-aluminum hydroxide gel reduced bioavailability by 90%. The data show that gastric pH does not affect absorption of oral tetracycline and that cimetidine can be used in place of antacids to control gastric acid in patients using tetracycline.

Adult↗

Effect of cimetidine on absorption of oral tetracycline in mice.

Gastric administration of cimetidine, 5 mg/kg, and magnesium aluminum hydroxide gel (Maalox), 1 ml/kg, were equally effective raising the gastric pH of mice from 2.5 to 5.0. The antacid depressed by 75% gastrointestinal absorption of tetracycline given by gastric tube at 25 mg/kg. Antibiotic bioavailability was measured by area under the plasma level-time curve, peak plasma level and urinary elimination. Cimetidine did not affect tetracycline absorption as reflected by any of these three parameters. If confirmed with the solid dosage form in man, the present study suggests that unlike magnesium aluminum hydroxide gel, cimetidine may be used as an effective means of reducing gastric acid in patients who take tetracycline.

Administration, Oral↗

A simple and sensitive nonradioactive method for the detection of urinary human chorionic gonadotropin and diagnosis of early human pregnancy. II. Single-unit test.

A simple, sensitive, and reliable single-unit nonradioactive method for the detection of human chorionic gonadotropin (hCG) in concentrated urine and the diagnosis of early pregnancy is reported. This unit, presently termed the Ayerst pregnancy test kit (APTK), consists of four components: a sampler-filter paper cone, an ultrafilter-concentrator to which a vial holder is attached, a support stand with a mirror, and an immunologic reagent vial. In the APTK, 5 to 6 ml of urine were sampled, filtered, and concentrated, and the hCG in the retentate was detected by Ayerst immunologic reagents [APTK(AY)] and by the Pregnosticon "All In" [APTK(P)]. Some of the unconcentrated urine samples (0.1 ml) were also tested in hemagglutination inhibition tests (HIT) using Ayerst [HIG(AY)] and Pregnosticon "All In" [HIT(P)] reagents. Urine samples from pregnant, nonpregnant (ovulating and nonovulating), perimenopausal, and menopausal women were tested. It was found that the APTK(AY) and APTK(P) were significantly more sensitive and reliable than the HIT(AY) and HIT(P) in detecting low levels of urinary hCG for early diagnosis of pregnancy. The sensitivity and specificity of the APTK(AY) were better than those of the APTK(P). The APTK(AY) give significantly more correct positive and negative results than the other tests performed simultaneously. The APTK(AY) is simpler and safer than the serum radioimmunoassays and radioreceptor assay presently used to detect low levels of hCG for the early diagnosis of pregnancy and other hCG-producing states.

Chorionic Gonadotropin↗

Drug uptake into everted intestinal sacs. I. Enhancement by hypertonicity.

The transfer of the cationic drugs, pralidoxime (PAM) and tetraethylammonium, and anionic ampicillin from the mucosal-to-serosal sides of everted rat jejunal sacs is enhanced by mucosal hypertonicity. PAM uptake, which is proportional to initial mucosal concentrations up to 2.3 mM, is enhanced by mucosal hypertonicity due to addition of sodium, potassium, lithium and choline chloride, sodium sulfate, and the nonionic solutes, urea, sucrose, and mannitol. Bicarbonate, Tris, or phosphate buffer and the presence of magnesium and calcium do not affect this hypertonicity-induced acceleration of PAM passage. Serosal osmolality has no effect on transfer and mucosal hypertonicity is equally effective in the presence and absence of a transmural osmotic gradient. This observation and minimal changes in the concentration of inulin placed in the sacs suggest that fluid shifts and solvent drag are not responsible for the enhanced mucosal-to-serosal transfer of PAM from hypertonic buffer. Mucosal hypertonicity at 450 mosmol/kg causes reversible enhancement of PAM transfer, whereas the effect of 600 mosmol/kg cannot be reversed by replacing the tissue in isotonic buffer. The effect of osmotic manipulation on PAM transfer across the intestine thus differs from its effect on the passage of other ionized species and drugs across other epithelia.

Ampicillin↗

Drug uptake into everted intestinal sacs. II. Inhibition of secretion by hypertonicity.

Mucosal hypertonicity, metabolic inhibitors, or absence of glucose and oxygen enhance mucosal-to-serosal influx of the cationic drug, pralidoxime (PAM), into sacs of everted rat jejunum in vitro. Conversely, efflux of PAM, which is twice the influx rate, is inhibited by mucosal hypertonicity or cyanide and iodoacetate. When sacs containing PAM, 0.87 mM, and glucose, 10 mM, were placed in identical drug- and sugar-containing mediums, the inside (serosal) concentration of PAM fell by over half in 120 min, whereas that of glucose more than doubled. Mucosal hypertonicity depressed PAM efflux and glucose influx regardless of serosal osmolarity. Although azide and mucosal hypertonicity each depressed glucose uptake and oxygen consumption while accelerating net PAM influx, azide more effectively depressed glucose and oxygen uptake, whereas hypertonicity caused greater acceleration of PAM uptake. Hypertonicity did not affect PAM binding to intestinal tissue. Varying mucosal pH did not change PAM or glucose uptake. Thus, mucosal hypertonicity apparently enhances net mucosal-to-serosal transfer of PAM by blocking its active secretion from serosa to mucosa.

Animals↗

Effect of enantiomeric purity on solubility determination of dexclamol hydrochloride.

The solubility of (+/-)-4a,13b-trans)-[3(OH),13b(H)-trans]-3-isopropyl - 2,3,4,4a,8,9,13b,14- octahydro-1H - benzo[6,7]cycloheptal[1,2,3-de]pyrido[2,1-a]isoquinolin-3-ol hydrochloride [(+/-)-I] was 3.3 mg/ml in pure water. Its resolved enantiomers exhibited about a fivefold increase in solubility. Dexclamol hydrochloride, the (+)-I enantiomer, is bioactive as a neuroleptic and is soluble to the extent of 16.4 mg/ml. However, raw material purity in relation to the amounts of (+/-)-I racemate present significantly influences solubility and optimum conditions for dissolution. The effect of trace amounts of (-)-I or (+/-)-I forms of the solubility of (+)-I enantiomer raw materials was explained through phase solubility studies. Conditions required for preparation of clear solutions using raw materials of varying purity can be determined with derived expressions. The application and limitations of using an enantiomer as a tool to improve solubility are discussed.

Dibenzocycloheptenes↗

Prolongation of gastric emptying by oral propantheline.

The present study shows that a single oral recommended dose of propantheline bromide normally doubles the mean gastric half-emptying time in man. In a prospective, double-blind, randomized crossover design 13 normal subjects were given 30 mg propantheline or placebo 90 min before taking a 113m-indium-labeled liquid test meal, the volume of which was adjusted to body weight. The disappearance of radioisotope from the area of the stomach was determined by external gamma counting. After placebo the mean half-emptying time was 68 min and after propantheline it was 135 min (p less than 0.005). Although salivary flow decreased and pulse rate increased there were no visual disturbances. In studies already reported maximally tolerated oral doses of quaternary ammonium anticholinergic drugs have not consistently retarded gastric emptying in man.

Adult↗

One-year trials with halofenate, clofibrate, and placebo.

The hypolipidemic as well as other laboratory and clinical effects of halofenate, clofibrate, and placebo were compared in 29 patients with type IV hyperlipoproteinemia in a double-blind, controlled, therapeutic trial of 1 yr duration. Plasma drug levels were obtained to monitor compliance. Clofibrate and halofenate lowered serum triglycerides to a similar extent. The hypotriglyceridemic effect of halofenate was significant only when data from noncompliant patients were discarded. Only clofibrate lowered baseline levels of plasma cholesterol. Very low density lipoproteins were decreased and low density lipoproteins were increased by clofibrate but not by halofenate. Halofenate had a marked hypouricemic effect that was greater than that of clofibrate. The hypouricemic effect of halofenate and clofibrate was paralleled by a concomitant decrease in serum bilirubin. Abnormal increases in serum creatine phosphokinase were observed with both drugs primarily in patients who had abnormal initial levels.

Adult↗

Analysis of butaclamol in serum by fluorescence induction.

A sensitive TLC-fluorometric method was developed for the analysis of butaclamol, a benzo[6,7]cyclohepta[1,2,3-de]-pyrido[2,1-a]isoquinoline derivative, in serum. The method involves cyclohexane extraction of serum samples followed by TLC of the concentrated extracts. The developed TLC plates were sprayed with an oxidizing reagent and heated at 110 degrees. Highly fluorescent spots were produced for butaclamol, which was well separated from metabolites and serum components. Fluorometric densitometry permitted quantitation with a sensitivity of 10 ng/spot application.

Adult↗

Effects of antacids on gastric emptying.

Aluminum hydroxide gel delays gastric emptying in rats and man. This effect of aluminum hydroxide gel varies with the concentration of aluminum in solution in the stomach when pH, osmolarity, and anion content are held constant. Because aluminum solubility drops as pH is raised, those antacids which neutralize more effectively than aluminum hydroxide gel alone and which contain "nonreactive" aluminum hydroxide result in lower aluminum concentration and do not affect the rate of gastric emptying in animals or in man. By using [51Cr]sodium chromate and a gamma camera technique, half-emptying time in 6 subjects with no gastrointestinal disease was shown to be prolonged from 13.1 min after water ingestion to 48.0 min after three hourly doses of aluminum hydroxide gel. Conventional nonabsorbable markers, including phenol red, were found to be of limited use for studying gastrointestinal function in the presence of antacid gels, most of which adsorb dyes.

Adolescent↗

The effects of endotoxemia and bacteremia on gastrointestinal drug absorption in mice and rats.

Endotoxin [lipopolysaccharide (LPS)] from four Gram-negative bacteria injected i.v. delayed absorption of drugs administered in solution by gastric tube to mice and rats. Salicylate and guinine absorption was delayed at LPS doses from 50 to 400 mug/kg. Salicylate absorption was delayed by LPS when drug was given by gastric tube, while LPS did not affect drug levels when salicylate was given i.p. or intraduodenally. Bethanechol prevented the LPS effect and LPS pretreatment also protected against delayed absorption. LPS- treated rats retained more drugs in their stomachs after 30 minutes and their plasma salicylate levels were lowered. Everted intestinal sacs from LPS-treated rats transferred salicylate as well as controls. Thus, LPS delays gastrointestinal drug absorption solely by retarding gastric emptying. Escherichia coli urinary tract infection did not reproduce LPS delay of drug absorption, but the effects of systemic bacteria were similar to those of endotoxemia.

Animals↗