Hemoperfusion in severe dimethoate poisoning.
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Charcoal↗
Biomedical subjects
C Köppel
Publications and source records attributed to C Köppel.
Fatal poisoning with selenium dioxide.
Two hours after suicidal ingestion of an unknown amount of selenium dioxide, a 17-year-old male was admitted to hospital with asystolia and apnea. Attempts at resuscitation failed and the patient was pronounced dead. Findings at autopsy included congestion of lungs and kidneys, diffuse swelling of the heart, and brain edema. The most impressive finding was an orange-brown discoloration of the skin and all viscera, probably due to hemolysis and/or pigmentation related to ingestion of selenium dioxide. Selenium blood and tissue levels were increased by a factor of 100-1000 as compared to normal. The highest concentrations were found in pancreas, spleen, liver, and adipose tissue. For elucidation of the chemical nature of selenium in tissues, a new analytical method which was based on carbon disulfide extraction was developed. Carbon disulfide is a good solvent for non-polar selenium compounds like elemental selenium and selenium disulfide, but not for polar compounds like selenite and selenoproteins. A major fraction of selenium in tissues was extractable by carbon disulfide, which seems to indicate the presence of elemental selenium and/or selenium disulfide. The color of these substances is red and orange, respectively. This might explain at least part of the discoloration of skin and tissues. In vitro experiments suggested that trace amounts of hydrogen selenide, which is an intermediate of selenite metabolism, probably induced hemolysis. For evaluation of the therapeutic value of hemoperfusion in selenium poisoning in vitro hemoperfusion experiments were performed, which revealed only a moderate effect on selenium blood levels.
Adolescent↗
Metabolism of chlormezanone in man.
The metabolism of chlormezanone (Muskel Trancopal) in man was studied by the aid of gas chromatography/mass spectrometry and high performance liquid chromatography after an oral dose of 400 mg. Six metabolites and/or degradation products were identified in the urine. Some of the metabolites are formed at least partially by nonenzymatic hydrolysis in the stomach. In contrast to previous publications, no unchanged drug was detected in plasma and urine. The main metabolite in plasma is generated by cleavage of the amide bond in the six-membered heterocyclic ring. This derivative is easily formed by in vitro hydrolysis at pH 1, too. It structurally resembles baclofene. About 40% of the dose is excreted with the urine. The major metabolite in urine is 4-chlorohippuric acid. Additionally, 4-chloro-benzoyl-N-methylamide, 4-chlorobenzoic acid, N-methylimino-4-chlorobenzaldehyde, 4-chlorobenzaldehyde, and "hydrolized" chlormezanone were identified.
Biotransformation↗
A revision of the metabolic disposition of amantadine.
Amantadine is one of the most commonly used drugs for the control of tremor in Parkinson's disease. Additionally, it has an antiviral action in the prevention of type A influenza. It has been previously reported that amantadine is nearly completely eliminated in the urine. No metabolites have been detected. Surprisingly, in a case of amantadine overdose, several metabolites could be identified by gas chromatography/mas spectrometry. This finding prompted us to re-investigate the metabolism of amantadine under a therapeutic dosing regimen. The bulk of the dose was eliminated unchanged. However, eight metabolites could be identified. Besides N-acetylation which is the major metabolic pathway, several rather unusual metabolic pathways were observed: N-methylation, formation of Schiff bases and N-formiates. No metabolites with a hydroxylated adamantane ring system could be detected.
Acetylation↗
Acute tetrachloroethylene poisoning--blood elimination kinetics during hyperventilation therapy.
After ingestion of 12-16 g tetrachloroethylene, a 6-year-old boy was admitted to the clinic in coma. In view of the high initial tetrachloroethylene blood level, hyperventilation therapy was performed. Under this therapeutic regimen, the clinical condition of the patient improved considerably. The tetrachloroethylene blood level profile which was determined under hyperventilation therapy could be computer-fitted to a two-compartment model. Elimination of tetrachloroethylene from the blood compartment occurred via a rapid and a slow process with half-lives of 30 min and 36 hours, respectively. These values compared favourably with the half-lives of 160 min and 33 hours under normal respiratory conditions. During hyperventilation therapy, the relative contribution to the fast elimination process increased from 70% for physiological minute volume to 99.9%. A minor fraction of the ingested dose was excreted with the urine (integral of 1% during the first 3 days). In contrast to previous results, trace amounts of unchanged tetrachloroethylene were detected in the urine besides trichloroacetic acid and trichloroethanol.
Acute Disease↗
The metabolism of tromantadine.
The metabolism of the antiviral drug tromantadine (1-adamantyl-2-(2-dimethylaminoethoxy)acetamide) was studied after an oral dose of 120 mg tromantadine hydrochloride using capillary gas chromatography/mass spectrometry. Most of the dose was excreted unchanged with the urine. Six metabolites could be identified. The main metabolic products were 1-aminoadamantane (amantadine) and 1-adamantyl-(2-hydroxy)acetamide. Further metabolic pathways were demethylation of the dimethylamino function and oxidative desamination to an unstable aldehyde which is oxidized to a carbonic acid or reduced to an alcohol.
Acetylation↗
Metabolism of benzydamine.
After an oral dose of 50 mg benzydamine to three volunteers, urinary metabolites were identified by mass spectrometric techniques. 50-65% of the dose was excreted unchanged with the urine. The main metabolic pathways were elimination of the dimethylaminopropyl group, elimination of the benzyl group, desmethylation, N-oxidation, and hydroxylation of the benzene ring. Didesmethylbenzydamine and hydroxybenzydamine were excreted in form of their corresponding glucuronides.
Benzydamine↗
Metabolism of propallylonal.
Urinary metabolism of 5-beta-bromoallyl-5-isopropylbarbituric acid (propallylonal, Noctal), was studied in humans after an oral dose of 400 mg. About 25% of the dose was eliminated via kidneys within 48 h. Besides the unchanged drug, six metabolites could be detected. The main metabolic pathway is the hydrolysis of the beta-bromoallyl side chain to an acetonyl function (approximately 15%). The acetonyl function is subsequently reduced to the corresponding alcohol. Loss of water leads to aprobarbital which is partially oxidized to aprobarbital epoxide. Two further metabolites are formed by partial and complete oxidative degradation of the beta-bromoallyl side chain. In contrast to previously published results, no N-methylpropyllalonal could be detected. The plasma protein binding was determined by ultrafiltration (63%). Analysis of propallylonal in plasma and whole blood gave evidence for equal distribution between plasma and erythrocytes.
Barbiturates↗
Tiaprofenic acid overdose.
After ingestion of 2000 mg tiaprofenic acid (Surgam), a 14-year-old girl was admitted to the clinic. The ingested dose was tolerated without signs of systemic intoxication. Tiaprofenic acid, its metabolites, and products of chemical decomposition were identified by gas chromatography/mass spectrometry in the urine sample of the patient. Additionally, a previously unknown decomposition product of a metabolite was detected. For quantitation of the drug in plasma, a rapid and sensitive high-performance liquid chromatography assay was established.
Adolescent↗
[Diagnostic value of urine analysis in drug addicts and rehabilitation patients].
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Humans↗
"Spanish old" not neurotoxic in rats.
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Animals↗
Methoxyethylmercury chloride poisoning: clinical findings and in vitro experiments.
A patient attempting suicide ingested 5682 mg methoxyethylmercury chloride, which corresponds to 4375 mg mercury. The bulk of the dose was eliminated by vomiting and gastric rinsing. About 706 to 977 mg mercury were absorbed in the gastrointestinal tract. Only 11.2 mg mercury could be removed by two activated charcoal hemoperfusions. Chelating agents were given for 12 weeks. The terminal elimination half-life calculated from blood and urine mercury levels was 23 and 25 d, respectively. No toxic effects on the kidneys and central nervous system were seen. The identification of methoxyethylmercury chloride in the gastric rinsing fluid was done by gas chromatography/mass spectrometry. The protein binding of methoxyethylmercury chloride was determined by ultrafiltration (93%). In the presence of dimercaprol sulfonate and penicillamine, protein binding was 83 and 88%, respectively. Activated charcoal and amberlite hemoperfusion revealed equal in vitro clearances for methoxyethylmercury chloride (62 mL/min at a flow rate of 80 mL/min).
Dimercaprol↗
Acute poisoning with pine oil - metabolism of monoterpenes.
A patient attempting suicide ingested 400-500 ml pine oil and was admitted to the clinic. Since more than the lethal dose had been ingested hemoperfusions with activated charcoal and amberlite and a hemodialysis were performed. The composition of the ingested pine oil was determined by gaschromatography/mass spectrometry. Four monoterpenes were identified: 57% alpha-pinene, 8% beta-pinene, 26% carene, 6% limonene and 3% other hydrocarbons. The blood and urine monoterpene concentrations were continuously monitored. The data suggest that monoterpenes are poorly resorbed in the gastrointestinal tract. The resorbed portion of the hydrocarbons cumulates in the lipophilic body compartments and is slowly metabolized and then excreted by the kidneys. The main metabolic pathways are hydratation, hydroxylation, rearrangement, and acetylation. Five metabolites were identified.
Bicyclic Monoterpenes↗
Chlormezanone plasma and blood levels in patients after single and repeated oral doses and after suicidal drug overdose.
Chlormezanone plasma concentrations were determined in 5 volunteers (group 1) after a single oral dose of 200 mg of chlormezanone with high performance liquid chromatography. A plasma elimination half-life of 23 +/- 2.3 h was calculated. The mean peak chlormezanone plasma level was 1.86 +/- 0.2 micrograms/ml, 1 h after ingestion. Additionally, chlormezanone plasma levels were determined after repeated oral doses of chlormezanone recommended for treatment of muscular spasms due to degenerative skeletal disease. After 5 days of repeated daily doses of 3 x 200 mg (group 2; 12 patients) or 3 x 400 mg (group 3; 10 patients) of chlormezanone, mean predose chlormezanone plasma levels were 12.0 +/- 2.0 micrograms/ml (group 2) and 22.7 +/- 4.0 micrograms/ml (group 3), respectively. Comparable plasma concentrations were determined after 10 days of repeated doses of 3 x 200 mg or 3 x 400 mg of chlormezanone in 3 patients from each of these 2 groups. In 7 patients of group 3, chlormezanone had to be discontinued on the 5th day due to increasing muscular weakness, ataxia and exercise-inducible tachycardia. After a loading dose of 800 mg and repeated doses of 3 x 200 mg chlormezanone to 5 patients (group 4), plasma levels of 6.5 +/- 2.1 micrograms/ml, 8.9 +/- 2.2 micrograms/ml, 12.7 +/- 2.0 micrograms/ml, and 10.4 +/- 2.4 micrograms/ml were determined after 2, 8, 16, and 36 h, respectively. Trace amounts of a degradation product of the acid-labile chlormezanone could be detected in plasma besides the unchanged drug after administration of repeated oral doses.(ABSTRACT TRUNCATED AT 250 WORDS)
Acetaminophen↗
Metabolic disposition of ajmaline.
Urine was collected from six patients receiving a continuous infusion of 20 mg/h ajmaline. Pooled urine was extracted with and without enzymatic conjugate cleavage or hydrolysis with concentrated hydrochloric acid. The extracts were analyzed by gas chromatography/mass spectrometry. Ajmaline and its metabolites in urine were identified in the form of their acetylated derivatives. Twenty two different acetylated derivatives of ajmaline and its metabolites could be detected. Three of these derivatives were artifacts generated by acetylation and/or thermal decomposition. The major metabolic pathways were mono- and di-hydroxylation of the benzene ring with subsequent O-methylation, reduction of the C-21, oxidation of the C-17 and C-21-hydroxyl function, N-oxidation, and a combination of these metabolic steps. Ajmaline and its metabolites were mainly excreted in the form of their conjugates. Furthermore, the interference of sparteine, debrisoquine, quinidine, and nifedipine with ajmaline metabolism was studied with semiquantitative thin-layer chromatography. Ajmaline metabolism was inhibited by co-administration of sparteine or quinidine, but not by debrisoquine or nifedipine. Sparteine most likely competed with ajmaline metabolism. Quinidine probably bound competitively to ajmaline-metabolizing enzymes without being metabolized itself. Additionally, the metabolic ratio of hydroxyajmaline/ajmaline in urine was determined in 9 extensive metabolizers and one poor metabolizer of dextromethorphan. The poor metabolizer had a significantly reduced metabolic ratio of hydroxyajmaline/ajmaline, which indicates that ajmaline metabolism probably co-segregates with polymorphic sparteine/debrisoquine/dextromethorphan metabolism.
Ajmaline↗
Rapid determination of functional liver plasma flow in ICU patients by a modified hepatic D-sorbitol plasma clearance method.
Changes in liver perfusion may have a substantial influence on the pharmacokinetics of drugs with flow-controlled metabolism. This may have important implications for drug dosage in patients in an intensive care unit (ICU). The hepatic D-sorbitol plasma clearance has been suggested as a non-invasive test for evaluating functional liver plasma flow, which is in reasonable agreement with the direct blood measurement. However, its determination requires D-sorbitol infusion for 3 h or administration of a D-sorbitol bolus and withdrawal of blood specimens every 3-5 min. Since both variants are impractical in the ICU setting, a bolus/infusion technique was tested. A combined technique applying a bolus (0.85 mg/kg) and steady-state infusion (0.0014 mg/kg/min) of D-sorbitol was tested in 10 ICU patients without hepatic disease (group 1) and in 10 ICU patients with liver disease (group 2). Steady-state plasma levels (+/- 9%, P < 0.05) could be achieved within 60 min in all patients. The modified D-sorbitol clearance method requires a bolus and an infusion of D-sorbitol and withdrawal of a single blood specimen after 60 min. The lowest values of functional liver plasma flow were determined in patients with decompensated liver cirrhosis, acute fatty degeneration of the liver or Budd-Chiari syndrome. The method for routine determination of functional hepatic plasma perfusion proved to be rapid, safe and non-invasive in ICU patients. Hepatic D-sorbitol clearance may be especially useful for assessing the functional aspect of liver perfusion.
Adult↗
Effects of enzyme induction, renal and cardiac function on ketamine plasma kinetics in patients with ketamine long-term analgosedation.
Steady-state plasma levels of ketamine and its metabolites norketamine and dehydronorketamine were determined in 4 different groups of a total of 27 patients with ketamine long-term analgosedation (1.1 - 1.3 mg/kg/h). In 9 of the patients who had normal liver and kidney function (group 1), steady-state levels after 3 days of continuous infusion were 1.2 +/- 0.3 micrograms/ml ketamine, 1.0 +/- 0.6 micrograms/ml norketamine, and 2.6 +/- 1.0 micrograms/ml dehydronorketamine. The measured ketamine levels in group 1 were in agreement with the expected value, which may be calculated from published pharmacokinetic data after bolus injection. In 8 patients with acute renal failure (group 2), a tendency to about 20% higher ketamine steady-state plasma levels compared to group 1 was observed, but this difference was not significant. However, dehydronorketamine plasma levels were significantly higher in this group. Only a minor fraction of the ketamine dose (10% and 4%) was eliminated during hemodialysis or hemofiltration treatment, respectively. Steady-state plasma levels in 5 patients with cardiogenic shock (group 3) did not differ significantly from those of group 1. In 5 patients with long-term use of barbiturates (group 4), steady-state plasma levels of ketamine were significantly lower compared to groups 1 and 3, most likely due to barbiturate-induced enzyme induction. Hyperdynamic circulatory reactions were not observed in any of the patients. Psychomimetic effects could be excluded in 16 of the patients and were unlikely in 6 patients. In 5 further patients, psychomimetic effects could not definitely be excluded due to difficulties in non-verbal communication.
Adult↗
Pharmacokinetics and antiarrhythmic efficacy of intravenous ajmaline in ventricular arrhythmia of acute onset.
21 patients with acute myocardial infarction and ventricular arrhythmia of Lown class II-IIIB of acute onset received a short infusion of (50 mg/5 min) ajmaline (Gilurytmal). 6 of the patients had normal kidney and liver function (Group 1), 4 patients had acute renal failure and hemodialysis treatment (Group 2), 4 patients had impaired hepatic function (Group 3), 3 patients had cardiogenic shock (Group 4), and 4 patients had been pretreated with phenobarbital for seizures for at least 5 days (Group 5). A distribution half-life of 6 +/- 1 min and an elimination half-life of 95 +/- 6 min was determined in Group 1. The total plasma clearance was significantly lower in patients with impaired liver or cardiac function and significantly higher in Group 5, whereas impaired renal function did not affect total plasma clearance. After short infusion, ventricular arrhythmia of Lown II-IIIB completely disappeared for at least 16 to 36 min (mean: 19 min), which was associated with an ajmaline plasma level of 0.1-0.45 micrograms/ml. Additionally, steady-state plasma levels of ajmaline were determined after continuous infusion of 10-50 mg/h to 16 patients (Group 6) with ventricular arrhythmia of acute onset (Lown class IVA-V). Ventricular arrhythmia completely disappeared or at least changed to lower Lown classes at ajmaline plasma levels of 0.4-2.0 micrograms/ml. The ajmaline plasma protein binding was 76 +/- 9%. Ajmaline had a special affinity to alpha 1-acid glycoprotein.
Acute Disease↗