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At least 55 records · Page 3Linked to original sources

Delayed salicylate toxicity at 35 hours without early manifestations following a single salicylate ingestion.

OBJECTIVE: To report a case of delayed toxicity following a single ingestion of aspirin, where the initial concentrations were nearly undetectable and the patient was completely asymptomatic for the first 35 hours. CASE SUMMARY: A 14-year-old white female was evaluated after a single ingestion of 120 tablets of aspirin 81 mg/tablet hours before arrival to the emergency department. She denied nausea, abdominal pain, tinnitus, or shortness of breath. She received one dose of activated charcoal. The first salicylate concentration (4 h after ingestion) was 1 mg/dL. At 35 hours, the patient became symptomatic (dizziness, tinnitus, epigastric discomfort). Her salicylate concentration at that time was 46 mg/dL. A second dose of activated charcoal was administered, and intravenous bicarbonate with potassium was started as a continuous infusion for 30 hours. DISCUSSION: While delayed salicylate toxicity is well reported in the literature, no report was found regarding concentrations increasing to toxicity 35 hours after ingestion. The delayed aspirin absorption may be due to salicylate-induced pylorospasm or the formation of pharmacobezoars. CONCLUSIONS: In cases with known salicylate ingestion, it is important to follow salicylate concentrations every 4 hours until they are steadily decreasing according to a 4-hour half-life and the patient shows no symptoms of salicylate intoxication.

Adolescent↗

A new salicylate ISFET for the determination of salicylic and acetylsalicylic acid in drugs.

A salicylate ISFET for the analysis of salicylic and acetylsalicylic acid in drugs is described. It is based on a salicylate ion selective membrane coated on the surface of the Si3N4 gate of the FET. The sensitive membrane consists of tetra-dodecylammonium salicylate, polyvinyl chloride and a proper plasticizer. The linearity range of the sensor is 5 x 10(-5)-1.5 x 10(-2) M for the salicylic acid, and 7 x 10(-5)-1.5 x 10(-2) M for the acetylsalicylic acid, respectively. The detection limit for the two compounds is 5 x 10(-5) M while the response time is < or = 20 s. The effect of pH and different interfering ions was also studied. The sensor was used to analyse the content of acetylsalicylic and salicylic acid in some drugs, and the accuracy of the method was evaluated through recovery tests. The results obtained with this method are well correlated either with those obtained with a classical ISE employing the same sensitive membrane or with the classical volumetric method.

Aspirin↗

The absorption of bismuth and salicylate from oral doses of Pepto-Bismol (bismuth salicylate).

Plasma bismuth and plasma salicylate concentrations were measured before and after three 30-ml oral doses of bismuth salicylate (Pepto-Bismol liquid) in 10 fasting healthy subjects. From 0 to 120 min following the first dose of bismuth salicylate, the plasma bismuth concentration was less than 1 ng/ml. The peak median plasma bismuth concentration was at +240 min (1.7 ng/ml; range 0.8-5.3 ng/ml). Salicylate appeared in the plasma of all subjects at +30 min, and it reached a peak at +120 min (median 61 mg/L; range 46-104 mg/L). The study demonstrates that, despite rapid and substantial absorption of salicylate, there is negligible absorption of bismuth into the bloodstream from standard oral doses of bismuth salicylate.

Adult↗

Salicylism from topical salicylates: review of the literature.

BACKGROUND: Although topical salicylates are widely used, toxicity from this route is rare. CASE REPORT: We present an unusual case of salicylism from a topical salicylate preparation in an 80-year-old woman. The patient was admitted to the dermatology service with a diagnosis of erythroderma and was treated with salicylate containing ointments. After six days of treatment the patient became confused and paranoid. A serum salicylate was 3.36 mmol/L (46 mg/dL). The patient was admitted to the intensive care unit were she was rehydrated and treated with bicarbonate and activated charcoal. RESULTS: Her serum salicylate fell to 1.90 mmol/L (26 mg/dL) over a two day period and she regained a normal mental status.

Acidosis↗

Adult salicylate poisoning: deaths and outcome in patients with high plasma salicylate concentrations.

The clinical features, plasma salicylate concentrations, acid-base abnormalities and other biochemical findings are presented for 97 patients who either died from acute salicylate overdosage or survived maximum recorded plasma salicylate concentrations of 700 mg/l or greater. These patients comprised 4 per cent of 2204 cases of salicylate poisoning admitted during the period 1975 to 1985 inclusive. Seven patients died (overall mortality 0.3 per cent); they were significantly older than the survivors, the mortality being as high as 33 per cent in patients over the age of 70 years. Delayed presentation, coma, hyperpyrexia, pulmonary oedema and acidaemia were more common in the fatal cases. Failure to hyperventilate appropriately may contribute to the development of acidaemia. The prognosis of acute salicylate poisoning cannot be determined from the plasma concentration of the drug alone. Clinical features, particularly impaired consciousness, and the arterial hydrogen ion concentration must be taken into consideration. Haemodialysis is the treatment of choice for severe salicylate intoxication and should be used more liberally than it is at present.

Adult↗

Interactions between sodium salicylate and acetyl salicylic acid evaluated using ADP induced platelet aggregation and bleeding time.

1 g acetyl salicylic acid orally significantly enhanced the initial rate of platelet aggregation induced by 1 mumol/l and 2.5 mumol/l ADP. Sodium salicylate was without effects on the platelet aggregation and specifically it did not prevent acetylsalicylic acid from inhibiting the secondary aggregation. Sodium salicylate was without effect on the bleeding time and did not inhibit the prolongation induced by acetyl salicylic acid. Our study does not lend support to the concept of an important interaction in vivo between acetyl salicylic acid and its first metabolite salicylate in man.

Adenosine Diphosphate↗

Determination of salicylate in blood serum by flow injection with immobilized salicylate hydroxylase.

A flow injection (FI) enzymatic system, based on the use of immobilized salicylate hydroxylase in glass beads, was developed for the determination of salicylate. Salicylate hydroxylase and nicotinamide adenine dinucleotide (NADH) are used to convert salicylate to catechol. The reaction of catechol with 4-aminophenol at high pH yields a colored product which is detected spectrophotometrically at 565 nm. Ten samples of human serum containing from 5.0 x 10(-4) to 5.0 x 10(-3) mol/L added salicylate were analyzed and the recovery was determined. Eight additional serum samples containing salicylate were analyzed by the Trinder test and the proposed method. The results obtained with the 2 methods showed good agreement by the statistical Student's t-test. The relative precision of the method is about 3.4% (RSD of the mean recovery). Considering the lowest concentration analyzed, the quantitative limit of detection is about 0.2 x 10(-5) mol/L (3 x SD). The volume of the sample used was 150 microL. The proposed method was also used to analyze medicines containing acetylsalicylic acid. The results were statistically compared with those obtained through the U.S. Pharmacopoeia procedure and showed excellent agreement.

Calibration↗

Model representation of salicylate pharmacokinetics using unbound plasma salicylate concentrations and metabolite urinary excretion rates following a single oral dose.

The pharmacokinetics of salicylic acid (SA) and its metabolites have been studied in 5 volunteers after administration of 3 g salicylic acid (as sodium salicylate) and collection of serial samples of blood and urine. SA and its metabolites were assayed with a HPLC method specific for each species. The urinary excretion rates of individual metabolites were analyzed using unbound plasma SA concentrations and Lineweaver-Burke plots. The analysis confirmed that the formation of SA urate (SU) and SA phenolic glucuronide (SPG) metabolites are saturable processes, and showed that the Michaelis-Menten values derived are consistent with earlier estimates derived solely from urinary data. The unbound salicylate plasma concentration-time profiles were then analyzed with various models assuming either saturable clearances for metabolite formation and/or saturable protein binding. The data were best described with a model that included both saturable protein binding and saturable metabolism. The model assumed first-order absorption kinetics and instantaneous distribution into extravascular and tissue compartments. The model was validated by comparing predicted relationships between the apparent volume of distribution, clearance, and plasma salicylate concentrations with previous relationships obtained using steady state data.

Administration, Oral↗

Direct analysis of salicylic acid, salicyl acyl glucuronide, salicyluric acid and gentisic acid in human plasma and urine by high-performance liquid chromatography.

A method for the simultaneous direct determination of salicylate (SA), its labile, reactive metabolite, salicyl acyl glucuronide (SAG), and two other major metabolites, salicyluric acid and gentisic acid in plasma and urine is described. Isocratic reversed-phase high performance liquid chromatography (HPLC) employed a 15-cm C18 column using methanol-acetonitrile-25 mM acetic acid as the mobile phase, resulting in HPLC analysis time of less than 20 min. Ultraviolet detection at 310 nm permitted analysis of SAG in plasma, but did not provide sensitivity for measurement of salicyl phenol glucuronide. Plasma or urine samples are stabilized immediately upon collection by adjustment of pH to 3-4 to prevent degradation of the labile acyl glucuronide metabolite. Plasma is then deproteinated with acetonitrile, dried and reconstituted for injection, whereas urine samples are simply diluted prior to injection on HPLC. m-Hydroxybenzoic acid served as the internal standard. Recoveries from plasma were greater than 85% for all four compounds over a range of 0.2-20 micrograms/ml and linearity was observed from 0.1-200 micrograms/ml and 5-2000 micrograms/ml for SA in plasma and urine, respectively. The method was validated to 0.2 microgram/ml, thus allowing accurate measurement of SA, and three major metabolites in plasma and urine of subjects and small animals administered salicylates. The method is unique by allowing quantitation of reactive SAG in plasma at levels well below 1% that of the parent compound, SA, as is observed in patients administered salicylates.

Chromatography, High Pressure Liquid↗

Novel S-adenosyl-L-methionine:salicylic acid carboxyl methyltransferase, an enzyme responsible for biosynthesis of methyl salicylate and methyl benzoate, is not involved in floral scent production in snapdragon flowers.

Using a functional genomic approach we have isolated and characterized a cDNA that encodes a salicylic acid carboxyl methyltransferase (SAMT) from Antirrhinum majus. The sequence of the protein encoded by SAMT has higher amino acid identity to Clarkia breweri SAMT than to snapdragon benzoic acid carboxyl methyltransferase (BAMT) (55 and 40% amino acid identity, respectively). Escherichia coli-expressed SAMT protein catalyzes the formation of the volatile ester methyl salicylate from salicylic acid with a K(m) value of 83 microM. It can also methylate benzoic acid to form methyl benzoate, but its K(m) value for benzoic acid is 1.72 mM. Snapdragon flowers do not emit methyl salicylate. The potential involvement of SAMT in production and emission of methyl benzoate in snapdragon flowers was analyzed by RNA gel blot analysis. SAMT mRNA was not detected in floral tissues by RNA blot hybridization, but low levels of SAMT gene expression were detected after real-time RT-PCR in the presence of SAMT-specific primers, indicating that this gene does not contribute significantly, if at all, in methyl benzoate production and emission in snapdragon flowers. Expression of SAMT in petal tissue was found to be induced by salicylic and jasmonic acid treatments.

Amino Acid Sequence↗

The pharmacokinetics of salicylate in dairy cattle are not altered by simultaneous intravenous ceftiofur sodium and DL-lysine-acetyl salicylate (aspirin).

This study evaluated potential alterations to the pharmacokinetics of salicylate by concurrently administered ceftiofur sodium. The trial design was a cross-over using 10 non-lactating, non-pregnant dairy cows. In the first period each cow received intravenously (i.v.) 26 mg/kg of DL-lysine acetyl salicylate (aspirin) followed immediately by 2 mg/kg ceftiofur sodium. In the second period each cow received 26 mg/kg of aspirin i.v. Plasma samples were harvested for determination of salicylate concentration by HPLC. The data best fitted a single compartment open model, using weighted non-linear regression. No alterations to the pharmacokinetic parameters of salicylate in cattle by concurrently administered ceftiofur sodium were detected (P < 0.05). Using 90% confidence intervals, and testing for changes of > 20%, control values, elimination half-life (t1/2), apparent volume of distribution (Vd), area under the plasma concentration versus time curve (AUC) and mean residence time (MRT) were not altered. For control animals the elimination rate constant (k(el)) and total body clearance (Cl) were 1.35 +/- 0.43 h-1 and 20.2 +/- 6.1 ml/h.kg respectively (mean +/- SD). Since ceftiofur sodium did not affect the pharmacokinetics of salicylate, dose regimens for aspirin in cattle need not be altered when ceftiofur sodium is administered concurrently.

Animals↗

Salicylate biosynthesis: overexpression, purification, and characterization of Irp9, a bifunctional salicylate synthase from Yersinia enterocolitica.

In some bacteria, salicylate is synthesized using the enzymes isochorismate synthase and isochorismate pyruvate lyase. In contrast, gene inactivation and complementation experiments with Yersinia enterocolitica suggest the synthesis of salicylate in the biosynthesis of the siderophore yersiniabactin involves a single protein, Irp9, which converts chorismate directly into salicylate. In the present study, Irp9 was for the first time heterologously expressed in Escherichia coli as a hexahistidine fusion protein, purified to near homogeneity, and characterized biochemically. The recombinant protein was found to be a dimer, each subunit of which has a molecular mass of 50 kDa. Enzyme assays, reverse-phase high-pressure liquid chromatography and 1H nuclear magnetic resonance (NMR) spectroscopic analyses confirmed that Irp9 is a salicylate synthase and converts chorismate to salicylate with a K(m) for chorismate of 4.2 microM and a k(cat) of 8 min(-1). The reaction was shown to proceed through the intermediate isochorismate, which was detected directly using 1H NMR spectroscopy.

Chorismic Acid↗

Relationship of plasma salicylate levels to pain relief with two different salicylates.

In a preliminary open study of salsalate (3 g daily for 4 weeks) in 61 patients with rheumatoid arthritis or osteoarthrosis, it was found that although the drug produced satisfactory analgesia in 64% of patients, the incidence of side-effects was high (57% of patients): most were symptoms of salicylism and probably related to the high plasma salicylate levels achieved. In a second open study, 20 patients with osteoarthrosis were treated for 4 weeks with 250 mg diflunisal twice daily and then crossed over to salsalate (3 g daily) for a further 2 weeks. The results of subjective assessments of pain relief showed that both drugs produced satisfactory analgesia, and neither was associated with a significant level of gastro-intestinal bleeding. During the diflunisal treatment period there were no reports of salicylism, and plasma salicylate levels were very much lower than those measured after salsalate. The pain relieving effects of both drugs, assessed from patient preference for one or the other treatment, were unrelated to the plasma salicylate levels and it is suggested that plasma levels may have more relationship to the incidence of side-effects than with therapeutic effects.

Analgesics↗

[Rheological phase synthesis and characterization of lanthanum salicylate and luminescence properties of Tb3+ -doped lanthanum salicylate].

Lanthanum salicylate and Tb3+ -doped lanthanum salicylate were synthesized with the rheological phase reaction method. Elemental analysis, IR, TG, DTA and powder X-ray diffraction were investigated to determine the composition, crystal structure and coordination manner between the COO- and ion La3+ of lanthanum salicylate. The emission and excitation spectra of Tb3+ -doped lanthanum salicylate were also discussed. Powder X-ray diffraction suggests that the compound has a layered monoclinic structure, and the lattice parameters are a = 21.6010 A, b = 13.8015 A , c = 3.8103 A, beta = 97.11 degrees, V = 1127.2 A3, Z = 2, rhocal = 1.621 g x cm(-3) and rhoexp = 1.653 g x cm(-3). The Tb3+ -doped lanthanum salicylate exhibits very strong green luminescence of Tb3+ under the excitation of UV light. And the transition from 5D4 to 7F5 is the strongest one.

Carbon Dioxide↗

Correlation of plateau serum salicylate level with rate of salicylate metabolism.

The range of plateau serum salicylate concentrations was 4.4 to 33 mg/100 ml in patients with rheumatoid arthritis after they were treated with 50 mg/kg of aspirin daily for 5 days. Individual plateau serum levels correlated better with urinary excretion rates of the metabolite, salicylurate (whose maximum production is capacity-limited), than with total urinary excretion of salicylates. These observations suggest that large intersubject variations in plateau serum salicylate levels are determined, at least in part, by similar differences in the maximum rates of capacity-limited metabolic reactions. For optimal therapeutic responses, individualization of aspirin dosage by following serum salicylate levels is recommended.

Administration, Oral↗

Interference with histamine and imidazole acetic acid metabolism by salicylates: a possible contribution to salicylate analgesic activity?

In man, rats and mice, the urinary excretion of the histamine and L-histidine metabolite, imidazole acetic acid, is increased and that of the conjugated metabolite, ribosylimidazole acetic acid, decreased by small doses of salicylates. In contrast to salicylates, other non-salicylate anti-inflammatory drugs, indomethacin, phenylbutazone, phenacetin and acetaminophen do not influence the excretion of the urinary metabolites of histamine and L-histidine. Since imidazole acetic acid is reported to have analgesic and narcotic activity, there is the inference that the analgesic properties of salicylate might be due in part to interference in imidazole acetic acid metabolism.

Adolescent↗