centras.lt

The objective of this research - to develop the methodics for analysis of amitriptyline, fluoxetine and codeine in the mixture. RESULTS. The analytical method of amitriptyline, codeine and fluoxetine in the mixture identification and quantitative determination using ultraviolet spectrophotometry was established. Preparations in the mixture can't be separated, because material ultraviolet light peaks are in insufficient distance and therefore cover one another. The maximum of ultraviolet light absorption for amitriptyline is at 217-220 and 238-240 nm; fluoxetine - at 226-228 nm; codeine - at 224-248 and 284-286 nm. Using ultraviolet spectroscopy it's possible to identify amitriptyline, fluoxetine and codeine only after separating mixture components by thin-layer chromatography, the same time executing cleaning of extracts from blood and urine. Using ultraviolet spectroscopy can be identificated at least 0.5 micro g/ml amitriptyline, 1.5 micro g/ml fluoxetine and 1.0 micro g/ml codeine. The intervals of the quantitative determination: 5-25 micro g/ml amitriptyline; 5-30 micro g/ml fluoxetine; 100-300 micro g/ml codeine; relative error of the measurement, when confidence level is 95%, is from 0.66 to 1.2% for amitriptyline; from 0.66 to 1.45% for fluoxetine; from 0.33 to 0.88% for codeine. Standard deviation is from 1.15 to 2.08% for amitriptyline; from 1.15 to 2.52% for fluoxetine; from 0.57 to 1.53% for codeine. Molar absorption coefficients for all three preparations in distillated water were determinated. Conclusions: recommended methodology suits for mixture, extracted from biological liquids, components separation, identification and quantitative determination.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14617875&dopt=Abstract Elavil amitriptyline[PubMed - in process]




Eur J Pharmacol. 2004 Feb 6;485(1-3):193-6.
Loss of amitriptyline analgesia in alpha(2A)-adrenoceptor deficient mice.

Ozdogan UK, Lahdesmaki J, Mansikka H, Scheinin M.

MediCity Research Laboratory, Department of Pharmacology and Clinical Pharmacology, University of Turku, Tykistokatu 6A, FIN-20520, Turku, Finland

Tricyclic antidepressants have analgesic and sedative effects in addition to their antidepressive properties. We tested the acute analgesic and locomotor inhibitory effects of the tricyclic antidepressant amitriptyline and the alpha(2)-adrenoceptor agonist clonidine in wild-type control and in alpha(2A)-adrenoceptor knockout mice in hot-plate and tail-flick tests. Amitriptyline-induced analgesia was lost in alpha(2A)-adrenoceptor knockout mice. The locomotor inhibitory effect of amitriptyline was reduced, but not fully abolished in alpha(2A)-adrenoceptor knockout mice. Similar results were obtained with clonidine. We conclude that alpha(2A)-adrenoceptors appear to have a significant role in amitriptyline-induced acute analgesia in mice, and that alpha(2A)-adrenoceptors also participate in the sedative effects of amitriptyline.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14757140&dopt=Abstract Elavil amitriptyline[PubMed - in process]

kyoritsu-ph.ac.jp

The cardiac toxicity of amitriptyline and the effect of the light schedule on it were studied in chick embryos. Fertilized eggs of White Leghorns were incubated under dark conditions and investigated, on two occasions, in the light phase and in the dark phase. Amitriptyline was injected into the air sac of fertilized eggs on the 16th day of incubation. Electrocardiograms were recorded 0 to 60 min after the injection. After the administration of amitriptyline 1 mg/egg in the light phase, the heart rate did not differ compared with that in controls. However, the heart rate was significantly decreased by the administration of amitriptyline 2.5 mg/egg and 5 mg/egg in the light phase. The heart rate was significantly decreased by the administration of amitriptyline 1 mg/egg under dark conditions. In addition, arrhythmia was produced by the administration of amitriptyline under dark conditions. These findings indicate that manipulation of the light schedule has a marked influence on the toxicity of amitriptyline in chick embryos.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14758040&dopt=Abstract Elavil amitriptyline[PubMed - in process]

vetmed.wsu.edu

A prospective study was performed to determine the relative availability of buspirone and amitriptyline after oral and transdermal routes of administration in 6 adult cats. For topical administration, drugs were compounded in a transdermal organogel containing pluronic and lecithin (PLO). Using a crossover design, each cat received a single dose of amitriptyline (5 mg) and buspirone (2.5 mg) by the transdermal and oral route of administration with at least a 2-week washout interval between drug treatments. Blood samples were obtained at 0, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours after drug administration for determination of plasma drug concentrations. Plasma concentrations of immunoreactive amitriptyline and buspirone were determined using commercial enzyme-linked immunosorbent assay (ELISA) tests. Systemic absorption of amitriptyline and buspirone administered by the transdermal route was poor compared with the oral route of administration. Until supporting pharmacokinetic data are available, veterinarians and cat owners should not rely on the transdermal route of administration for treating cats with amitriptyline or buspirone.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14765730&dopt=Abstract Elavil amitriptyline[PubMed - in process]




J Chromatogr. 1992 Dec 23;584(2):249-55.
High-performance liquid chromatographic determination of amitriptyline and its main metabolites using a silica column with reversed-phase eluent. Application in mice.

Coudore F, Ardid D, Eschalier A, Lavarenne J, Fialip J.

Laboratoire de Pharmacologie Medicale, INSERM U195, Faculte de Medecine, Clermont-Ferrand, France.

A method was developed for the assay of amitriptyline, amitriptyline N-oxide, nortriptyline, desmethylnortriptyline and E (trans) and Z (cis) isomers of 10-hydroxy amitriptyline and of 10-hydroxynortriptyline in plasma and brain of animals, using high-performance liquid chromatography with ultraviolet detection (254 nm). Single extraction was performed at pH 10.5 from 0.25 ml of plasma or 1 ml of brain mixture. Chromatographic separations were achieved with a silica column and an aqueous methanol mobile phase containing ammonia. This procedure offers high sensitivity (8-10 ng/ml), high linearity (r > 0.99) and acceptable precision (coefficient of variation < or = 13.3%). The method was used to determine levels of amitriptyline and its major metabolites in mice 30 min after a single intraperitoneal administration of amitriptyline (20 mg/kg).

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1484109&dopt=Abstract Elavil amitriptyline




Ther Drug Monit. 1992 Feb;14(1):1-8.
Dextromethorphan and mephenytoin phenotyping of patients treated with thioridazine or amitriptyline.

Baumann P, Meyer JW, Amey M, Baettig D, Bryois C, Jonzier-Perey M, Koeb L, Monney C, Woggon B.

University Department of Adult Psychiatry, Hopital de Cery, Prilly-Lausanne, Switzerland.

The metabolism of most tricyclic antidepressants and some phenothiazine neuroleptics is under the genetic control of hepatic cytochrome P-450IID6, which also regulates the metabolism of dextromethorphan. This study investigated the effect of treatment with amitriptyline or thioridazine on testing for genetically regulated efficiency of the metabolism of dextromethorphan and mephenytoin. One group of 33 patients was treated with 150 mg amitriptyline a day (the AMI group); 25 other patients received a daily dose of thioridazine, either 200 mg (200-THD group; n = 7) or 400 mg (400-THD group; n = 18). Before and after 10 days of this treatment, all patients were tested with 25 mg dextromethorphan and 100 mg mephenytoin to determine their pharmacogenetic status with respect to their hepatic drug oxidizing systems (cytochrome P-450IID6 and P-450 MP). Two patients were poor metabolizers (PMs) of dextromethorphan and three of mephenytoin. Treatment with either psychotropic drug was without significant effect on the metabolism of mephenytoin, but both amitriptyline and thioridazine increased significantly the metabolic ratio of dextromethorphan/dextrorphan. Thioridazine had the effect of changing the pharmacogenetic status of 15 efficient metabolizers of dextromethorphan to poor metabolizers; amitriptyline did not have such an effect. There was no significant correlation between day-11 plasma levels of thioridazine, mesoridazine, or sulforidazine and the metabolism of dextromethorphan, but there was a correlation between the metabolism of dextromethorphan and plasma levels of amitriptyline and nortriptyline. Amitriptyline (p less than 0.05), but not thioridazine, decreases the ratio of conjugated/total dextrorphan in urine.(ABSTRACT TRUNCATED AT 250 WORDS)

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J Toxicol Clin Toxicol. 1992;30(2):171-9.
Severe amitriptyline overdose: relationship between toxicokinetics and toxicodynamics.

Hulten BA, Heath A, Knudsen K, Nyberg G, Starmark JE, Martensson E.

Department of Anaesthesia and Intensive Care, Lillhagens Hospital, Gothenburg, Sweden.

The clinical features and toxicokinetics of amitriptyline were studied in nine patients with severe amitriptyline poisoning. Amitriptyline and amitriptyline metabolites were studied in plasma, red blood cells, and cerebral spinal fluid. Eight patients were intubated and six required assisted ventilation. Two patients had ventricular arrhythmias, three patients convulsions and two were hypotensive. All complications developed within four hours of admission. Early in the course of the intoxication the QRS duration correlated with plasma, unbound and red blood cell nortriptyline concentration. The QRS duration also correlated with unbound but not the plasma amitriptyline concentration. The level of consciousness correlated with the plasma and unbound amitriptyline both in alpha and beta phase and with red blood cell amitriptyline in alpha phase. There was no correlation between nortriptyline concentration and level of consciousness. No correlation between coma grade or QRS duration and cerebral spinal fluid concentration of amitriptyline was found. There was no correlation between any hydroxymetabolite in blood or cerebral spinal fluid and QRS duration or coma grade. The beta half-life for amitriptyline was shorter for two patients with high concentrations of hydroxymetabolites. Although intubated, neither patient required assisted ventilation or developed complications. Because of the wide range of concentrations of amitriptyline and amitriptyline metabolites observed between individuals, it is not possible to predict outcome based on a single tricyclic antidepressant concentration.

Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1588667&dopt=Abstract Elavil amitriptyline