Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “SALICYLAMIDE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1979

Radiochemical plasma salicylamide assay using ring-labeled tritiated salicylamide.

A rat plasma salicylamide assay was developed using ring-labeled tritiated salicylamide, synthesized by reacting salicylamide with tritium oxide in the presence of heptafluorobutyric acid. The reaction yielded 3H-salicylamide of specific activity up to 8.41 mCi/mmole, 60% yield. Plasma containing 3H-salicylamide and its metabolites was extracted with a toluene-based scintillation fluid, which was subsequently counted. Specificity for free salicylamide was demonstrated by radio chemical and standard fluorescence plasma salicylamide level-time curves. Specificity resulted from nonextraction of the salicylamide sulfate and glucuronide metabolites. Sulfatase and beta-glucuronidase treatment allowed the analysis of plasma sulfate and glucuronide conjugates as free salicylamide. This procedure should be effective for the analysis of salicylamide and its metabolites in the presence of similar phenolic compounds.

Animals↗
PubMed1982

Arylethanolamines derived from salicylamide with alpha- and beta-adrenoceptor blocking activities. Preparation of labetalol, its enantiomers, and related salicylamides.

A series of phenethanolamines (3) based on salicylamide has been prepared and shown to possess beta-adrenergic blocking properties. When the basic nitrogen atom was substituted by some aralkyl groups, the compounds also blocked alpha-adrenoceptors. The 1-methyl-3-phenylpropyl derivative labetalol (34) is antihypertensive in animals and man, and syntheses of its four stereoisomers are described. The enantiomer 90 with the R configuration at both asymmetric centers possessed most of the beta-blocking activity but little alpha-blocking activity. That with the S configuration at the alcoholic carbon and the R configuration on the amino substituent, 89, is predominantly an alpha-adrenoceptor blocking agent.

Adrenergic alpha-Antagonists↗
PubMed1983

Determination of salicylamide and five metabolites in biological fluids by high-performance liquid chromatography.

Two high-performance liquid chromatographic (HPLC) assay procedures were developed for the determination of salicylamide and its metabolites in serum, urine, and saliva. One method involves reverse-phase ion-pair chromatography and UV detection, and is used to determine salicylamide, salicylamide glucuronide, and salicylamide sulfate. The other method, with a different mobile phase and without the ion-pairing reagent, is used to determine gentisamide (the hydroxylated metabolite of salicylamide), gentisamide glucuronide, and gentisamide sulfate. The assays are performed by direct injection of the sample after protein precipitation with ethanol containing the internal standard. Increased sensitivity for the determination of low concentrations of salicylamide is obtained by organic extraction of this drug from serum or saliva. Calibration curves for the conjugates of salicylamide and gentisamide were obtained, in the absence of authentic standards, by partial enzymatic hydrolysis, using the decrease of the conjugate peaks and the concomitant increase of free salicylamide or gentisamide concentrations to determine peak area ratio-concentration relationships. Application of the HPLC assay procedures to the determination of salicylamide excretion products in the urine of three normal human subjects resulted in 98.6% (range:97.1-100.1%) recovery of a 1-g oral dose of the drug. All five metabolites of salicylamide were found in urine, but only salicylamide glucuronide, salicylamide sulfate, and gentisamide glucuronide were found consistently and in appreciable quantities. Salicylamide and all of its metabolites except gentisamide sulfate were found in human and rat serum, and unconjugated salicylamide as well as gentisamide were found in human saliva.

Animals↗
PubMed2003

Adsorption and entrapment of salicylamide molecules into the mesoporous structure of folded sheets mesoporous material (FSM-16).

PURPOSE: The aim of this study was to estimate the molecular state of salicylamide on the surface of mesoporous silicas and to investigate the dissolution behavior of salicylamide from the solid dispersion. METHODS: Folded sheets mesoporous material (FSM-16) were used as a porous material. The molecular state of salicylamide was estimated by powder X-ray diffractometry, infrared spectroscopy, and fluorescence spectroscopy. RESULTS: The molecular state of salicylamide can be changed by simple blending with FSM-16. When a physical mixture of 25% salicylamide and 75% FSM-16 was heated at 120 degrees C for 3 h, amorphization of salicylamide was observed from the powder X-ray diffraction pattern. The fluorescence emission peak of salicylamide at 433.5 nm shifted to a longer wavelength of 447.5 nm after heating. Changes in fluorescence decay curve suggested that salicylamide molecules were dispersed into the hexagonal FSM-16 channels during the heating process. Enhanced dissolution in the initial stage of salicylamide from the sealed heated sample was observed in comparison with salicylamide crystals. CONCLUSIONS: Heat treatment of a physical mixture of salicylamide with FSM-16 gave a solid dispersion in which the salicylamide molecules changed to an amorphous state by adsorption onto the FSM-16 channels. Amorphization of salicylamide contributed to the improvement of dissolution.

Calorimetry, Differential Scanning↗
PubMed1988

3-Hydroxylation of salicylamide in mice.

Salicylamide is an important model compound for use in investigations concerning drug disposition. In this study the metabolic fate of salicylamide at high doses was evaluated in male mice using HPLC methodology. The concentrations of salicylamide and its metabolites were determined in urine and in blood at various times after the administration of 2 or 4 mmol kg-1 salicylamide. Salicylamide, gentisamide, and their glucuronide and sulfate conjugates were detected. 2,3-Dihydroxybenzamide, the 3-hydroxy metabolite of salicylamide, as well as its glucuronide and sulfate conjugates, were identified and quantitated for the first time by HPLC. 2,3-Dihydroxybenzamide had previously been detected only as a minor metabolite of salicylamide by paper chromatography. However, in the present study, 18% of the salicylamide metabolites appearing in urine after either dosage of salicylamide were 3-hydroxylation products. When a previously published HPLC method for salicylamide analysis was used, 2,3-dihydroxybenzamide glucuronide coeluted with salicylamide glucuronide. The possible formation of 3-hydroxy metabolites must be evaluated in any study of drug metabolism using salicylamide as a model compound.

Animals↗
PubMed1976

Effect of route of administration on competitive drug biotransformation interaction: salicylamide-ascorbic acid interaction in rats.

The effect of route of administration on competitive drug biotransformation interactions was explored with respect to the interaction between salicylamide and ascorbic acid. Previous studies in man have shown that this interaction involves competition for available sulfate and consequent inhibition of drug sulfate formation. Adult rats received salicylamide (100 mg/kg i.v. or 500 mg/kg orally) alone or with ascorbic acid (500 mg/kg i.v. or orally). Plasma concentrations and urinary excretion rates of salicylamide, salicylamide glucuronide and salicylamide sulfate were determined as a function of time. With i.v. salicylamide, i.v. ascorbic acid caused a modest decrease of salicylamide sulfate formation and thereby of salicylamide body clearance. Orally administered vitamin had a somewhat more pronounced effect. The vitamin had no effect on the apparent volume of distribution of salicylamide and on the renal clearances of its conjugates. With orally administered salicylamide, oral ascorbic acid caused a very pronounced decrease of salicylamide sulfate formation and salicylamide body clearance, whereas intravenous vitamin had little or no effect. These observations are consistent with the assumption that the magnitude of competitive drug biotransformation interactions, being a function of concentration, is most pronounced when the interactants are co-administered orally, due to their high concentrations in the intestinal wall and liver during the first pass.

Administration, Oral↗
PubMed1981

Effect of salicylamide on skeletal glycosaminoglycan sulfation and calcification in fetal rat limbs.

It has been shown that the non-narcotic analgesic salicylamide is teratogenic for rats. When this drug is administered to rats during gestation, sulfate incorporation into the fetal skeleton is reduced. Aims of studies reported here were to examine the effect of salicylamide on the incorporation of radiosulfate into glycosaminoglycans (GAGs) and the biosynthesis of chondroitin 4-sulfate (Ch-4-S) and chondroitin 6-sulfate (Ch-6-S) in fetal rat limbs was studied. Pregnant rats were fed 25% casein diet with or without 2% salicylamide from day 6 to day 17 or day 19 of gestation. The dams were killed on day 17 or day 19 of gestation, 24 hours following an intramuscular injection of sodium 35S-sulfate. Salicylamide administration decreased the levels of radiosulfate in maternal serum and placenta, and impaired the incorporation of radiosulfate into fetal skeletal GAGs. The incorporation of radiosulfate into fetal skeletal GAGs was significantly affected by maternal serum 35S-sulfate, placental 35S-sulfate, litter size, placental weight and fetal weight. After adjusting for these variables, salicylamide administration still had a significant effect, suggesting that salicylamide may have a primary effect in impairing the incorporation of sulfate into fetal skeletal GAGs. Salicylamide administration was found to have no significant effect on the amount of radiosulfate incorporated into Ch-4-S relative to that incorporated into Ch-6-S. The results showed that with increasing gestational age, there was an increase in synthesis of Ch-4-S with a concomitant decrease in synthesis of Ch-6-S. The effect of salicylamide on the calcification of fetal skeletons was studied. Salicylamide administration resulted in a decrease in the calcium content of fetal limb bones, but had no significant effect on maternal serum calcium. The calcium content of fetal limb bones was greatly affected by fetal weight. After adjusting for the fetal weight effect, salicylamide still had a significant effect on the calcium content of fetal limb bones. These results suggest that the degree of sulfation of fetal skeletal GAGs affects the calcification of fetal skeletons.

Animals↗
PubMed1994

Demonstration of rapid entry and a cellular binding space for salicylamide in perfused rat liver: a multiple indicator dilution study.

The kinetics of influx, efflux and removal of salicylamide under steady-state conditions (input concentration, 9-870 microM) were studied with the single pass erythrocyte-perfused rat liver in the absence of albumin (12 ml min-1). A substantial distribution of salicylamide into red blood cells (red cell/plasma ratio, 3.5) was observed. During steady state, a bolus dose containing multiple indicators (51Cr-labeled red cells (vascular space marker), [3H]sucrose (interstitial space marker), D2O (cellular space marker) and added [14C]salicylamide tracer) was injected into the portal vein. The steady-state hepatic salicylamide extraction ratio decreased from 0.99 to 0.4 over the concentration range used. The extraction ratio for bulk salicylamide was similar to 1 minus the integral of the fractional outflow recovery of unchanged tracer [14C]salicylamide (or [1-F] where F is the availability). Modeling of the indicator dilution outflow data revealed an extremely rapid (flow-limited) influx and efflux for salicylamide that was independent of the partitioning of salicylamide into red blood cells. The decrease in extraction ratio was due solely to saturation of the metabolic processes, shown previously to be sulfation, glucuronidation and hydroxylation. The sequestration rate constant, representing the pooled constant for all of the metabolic pathways, decreased from 0.45 to 0.035 sec-1 with increase in concentration. From the spectrum of its change with concentration, calculated values for a corresponding apparent Vmax and Km were 17.5 nmol sec-1 ml-1 cellular water and 27 microM, respectively. The cellular distribution space for salicylamide was exceedingly large, 20 times the size of the cellular water space, at trace levels, and fell to a constant level (5 times the cellular water space) with increasing concentration. The phenomenon, first observed for n-propanol (Goresky et al., Am. J Physiol. 244: G215-G244, 1983a), is explained by a nonsaturable (partition coefficient, 3.8-5) and a saturable binding (binding site concentration, 352-98 microM) component in the tissue. The binding effects inverted the order of elution of the parent and metabolite profiles; the outflow emergence of metabolites began earlier than that of the parent compound, salicylamide.

Animals↗
PubMed1994

Salicylamide sulfate cell entry in perfused rat liver: a multiple-indicator dilution study.

The hepatocellular entry of salicylamide sulfate conjugate, which binds to both red blood cells and albumin, was examined with the multiple-indicator dilution technique in the perfused rat liver, with medium containing both 20% red cells and 1% albumin (set A), red cells only (set B), albumin only (set C) and neither red cells nor albumin (set D). [14C]Salicylamide sulfate, 51Cr-labeled red cells (a vascular reference), 125I-labeled albumin, [3H]sucrose or [58Co] ethylenediaminetetraacetic acid (EDTA) (high and low molecular weight interstitial references, respectively) and 3H2O or D2O (a cellular reference) were injected as a bolus into the portal vein. Among all sets of outflow data, the earliest immediate vascular recoveries for the [14C] salicylamide sulfate were lower than those for the vascular reference. For sets A and B, the upslopes precessed those for the 58Co-EDTA curve, then crossed over the 58Co-EDTA curves, with lower magnitude peaks occurring at the same time as those for labeled albumin, whereas for sets C and D, in which red cells were absent, the upslopes of [14C]salicylamide sulfate lagged behind those for labeled albumin and [3H]sucrose, reaching lower magnitude peaks coincidental in time with those for labeled sucrose. The precession of the [14C]salicylamide sulfate curve over 58Co-EDTA or [3H]sucrose in the presence (sets A and B) but not in the absence (sets C and D) of red cells and the absence of precession with albumin alone (set C) suggest that a red cell effect on the upslope is more evident than that for albumin. For all experiments, the downslopes of the sulfate curve crossed over those of the labeled red cells, albumin, 58Co-EDTA and sucrose curves and then the water curve at around the peak. The downslopes of the [14C]salicylamide sulfate were similar to those for labeled water, suggesting rapid cellular influx and efflux of salicylamide sulfate. Quantitative evaluation with a barrier-limited space-variable transit-time model for rapidly equilibrating red cell and albumin binding accounted for the upslope effects on [14C]salicylamide sulfate behavior and demonstrated its relatively high liver cell permeability. Values for the unbound permeability surface area product (0.029 to 0.036 ml sec-1.gm-1) were not different, regardless of the presence or absence of red cells and albumin, and slightly exceeded values for hepatic blood flow (0.0186 +/- 0.0016 ml sec-1.gm-1). Comparable influx (0.083 to 0.14 sec-1) and efflux (0.10 to 0.18 sec-1) coefficients were obtained, suggesting rapid cellular entry and efflux of salicylamide sulfate.(ABSTRACT TRUNCATED AT 400 WORDS)

Albumins↗
PubMed1981

Sulfoconjugation and glucuronidation of salicylamide in isolated rat hepatocytes.

Sulfoconjugation and glucuronidation of salicylamide by isolated hepatocytes were examined with various concentrations of salicylamide and sodium sulfate. The ratio of sulfate to glucuronide formed changed markedly, depending on the concentrations of salicylamide and inorganic sulfate in the medium. The apparent Km value of sulfoconjugation for salicylamide was 0.006 mM, while its Vmax value varied depending on the concentration of inorganic sulfate (e.g., 2.1 and 0.5 nmoles/min/10(6) cells at 1.2 and 0.5 mM inorganic sulfate, respectively). The Km and Vmax values of glucuronidation for salicylamide were 0.19 mM and 1.28 nmoles/min/10(6) cells, respectively, in the absence of sodium sulfate. Glucuronidation was suppressed in the presence of inorganic sulfate. The suppression could be attributable to the competitive consumption of salicylamide by sulfotransferase. Additional in vivo experiments revealed that an extra amount of salicylamide markedly lowered the blood inorganic sulfate levels of rats. The significance of the finding is discussed in conjunction with the variation of the Vmax value of sulfoconjugation with the inorganic sulfate concentration.

Animals↗
PubMed1988

Time-dependent, plasma-sulfate-independent kinetics of salicylamide in dogs.

The mechanisms of the dose-dependent elimination kinetics of salicylamide in dogs were examined. Salicylamide was infused continuously over three consecutive 90-min periods. The rates of infusion during Periods I and III were the same. During Period II the infusion rate was 2.5-fold higher. Plasma concentrations of inorganic sulfate were kept constant by the administration of exogenous sulfate. The plasma concentrations of salicylamide, which reached steady state during Period I but not during II or III, were twice as high at the end of Period III than those at the end of Period I. Typical Michaelis-Menten kinetics do not explain these results. When salicylamide was given as 40 mg/kg single oral dose, clearance of an intravenous tracer dose of radiolabeled salicylamide was greatly reduced within 10 min but returned to baseline values by 240 min after the oral dose, despite persistently low plasma concentrations of inorganic sulfate. Therefore, dose- and time-dependent factors other than Michaelis-Menten kinetics, depletion of inorganic sulfate concentrations, and rate limitation of supply of "active sulfate" from plasma inorganic sulfate stores produce the dose- and time-dependent kinetics of salicylamide in the dog. Product inhibition of salicylamide sulfoconjugation remains a possible explanation.

Administration, Oral↗
PubMed1984

Difference in hepatic uptake kinetics of aspirin and salicylamide in rats.

Immediately after intraportal administration to rats, the ratio of liver to plasma concentrations for total aspirin was close to unity, whereas that for total salicylamide ranged from about 3 to 7. The hepatic accumulation of salicylamide appeared to be capacity-limited because the ratio decreased with increases in the dose. In vitro experiments with isolated hepatocytes indicated that aspirin was slowly transported into the hepatocytes by an apparently linear process only, while salicylamide was taken up very rapidly by both saturable and apparently linear transport processes. The cell to medium concentration ratio estimated for the initially net transported component of the unchanged drug was significantly larger with salicylamide, which give ratios from 3.5 to 19, than with aspirin which gave an almost constant value lower than 2 despite wide variations in the initial concentration. For the capacity-limited uptake process of salicylamide, the kinetic parameters were estimated as Vmax = 0.325 nmole X (mg cellular protein)-1 X sec-1 and Km = 201 microM. Among various metabolic inhibitors, 2,4-dinitrophenol (50 microM) inhibited the uptake of salicylamide most extensively. The present comparison of the in vivo and in vitro data for aspirin with those for salicylamide confirmed the previously reported difference in the hepatic first-pass effect of these two drugs.

2,4-Dinitrophenol↗
PubMed1978

Effect of salicylamide on the placental transfer and fetal tissue distribution of sodium-35S-sulfate in the rat.

Pregnant rats were used to determine effects of salicylamide on the sequential uptake and loss of radiosulfate by maternal and fetal tissues. Separate and combined effects of salicylamide and protein restrictions on radiosulfate retention by fetal rat tissues were determined. Rats were fed salicylamide-containing or control diets from the 4th or 6th day of gestation. Rats were killed between the 17th and 19th days of gestation, following intramuscular injection of sodium-35S-sulfate. Fetal and placental radiosulfate uptake was related to maternal serum levels. Salicylamide administration decreased radiosulfate uptake by maternal serum and liver, fetus and placenta--effects being dose-dependent. Differences in radiosulfate uptake by the fetus and placenta over time, induced by salicylamide, were also significant independently of maternal serum levels of radiosulfate. Major retention of 35S was found in the fetal cartilage with lower concentrations in the fetal skin, intestine, brain and liver. Protein restriction increased retention of 35S, and salicylamide administration caused a significant reduction in 35S retention by fetal tissues. Skeletal malformations were found in fetuses from dams receiving salicylamide. It is concluded that this drug lowers the availability of sulfate to the fetus from the dam, impairs the incorporation of sulfate by fetal tissues utilizing sulfates, and is teratogenic.

Abnormalities, Drug-Induced↗
PubMed1976

Sodium salicylamide: relative bioavailability and subjective effects.

The bioavailability of sodium salicylamide (NaSAM) in solution of salicylamide (SAM) tablets was compared in 6 healthy human volunteers. Bioavailability was assessed by plasma level determinations of nonmetabolized salicylamide (free SAM) and salicylamide plus conjugated metabolites (total SAM) for 3 hr following oral doses of 0.65, 1.30, 1.95, and 2.60 gm of salicylamide. The availability of NaSAM was found to be superior to SAM and dose-dependent. Mean peak levels of free SAM and total SAM were higher and were reached earlier after NaSAM liquid than after SAM tablets. Significantly higher mean levels of free SAM were found at the 1.95 and 2.60 gm dose levels after NaSAM administration than after SAM. Mean total SAM concentration was significantly higher after NaSAM at all dosage levels. The sedative effects of salicylamide were assessed with a self-scoring questionnaire. Sedation seemed to increase with increasing dose of both NaSAM and SAM. The sedative response occurred earlier after NaSAM than after SAM. Side effects were minor and transient in nature, occurred at the higher dosage levels, and were predominantly lightheadedness and dizziness. Because NaSAM produces higher drug levels and has a more rapid onset of subjective effects, we conclude that it represents a potentially superior dosage form.

Biological Availability↗
PubMed1978

Effect of salicylamide and acetaminophen on dextromethorphan hydrobromide metabolism: possible pharmacological implications.

The effect of salicylamide and acetaminophen on the metabolic fate of dextrorphan, the primary metabolite of dextromethorphan, was studied in vivo in the rat. Plasma dextrorphan levels were measured at 5-min intervals up to 20 min and at longer intervals up to 2 hr after dextromethorphan hydrobromide was administered orally either alone or in combination with salicylamide and acetaminophen. The combination gave rise to higher plasma dextrorphan levels than did dextromethorphan hydrobromide alone at most sampling times. Conjugation of dextrorphan was inhibited almost quantitatively by salicylamide and acetaminophen at the 5-min sampling time. Salicylamide alone increased the plasma dextrorphan levels when it was coadministered with dextromethorphan, but the differences were not statistically significant. The antitussive activity of dextromethorphan hydrobromide in the unanesthetized dog was faster in onset, greater in intensity, and longer in duration when it was coadministered with salicylamide and acetaminophen. It is suggested that salicylamide and acetaminophen may inhibit the metabolic inactivation of dextrorphan, thereby improving the coughinhibiting potential of dextromethorphan hydrobromide.

Acetaminophen↗