In Vitro and in Vivo Study of the Antithyroid Side Effects of Trimeprazine

Sauvage, Marie-Frédérique; Rousseau, Annick; Marquet, Pierre; Dumeirain, F.; Raby, C; Lachâtre, Gérard

doi:10.1006/taap.1999.8699

Toxicology and Applied Pharmacology

1999

DOI: 10.1006/taap.1999.8699

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In Vitro and in Vivo Study of the Antithyroid Side Effects of Trimeprazine

Marie-Frédérique Sauvage

Annick Rousseau

Pierre Marquet

et al.

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Cited by 2 publications

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“…However, high doses of this drug may cause side effects such as photosensitive dermatitis, drowsiness, abdominal discomfort and reduction in the level of serum thyroid hormones 1–3. Various methods have been applied for the separation and determination of trimeprazine in different matrices including high‐performance liquid chromatography (HPLC),4, 5 capillary electrophoresis (CE),6 flow injection analysis (FIA),7, 8 ultraviolet‐visible (UV‐VIS) spectrophotometry,9 liquid chromatography/mass spectrometry (LC/MS),10 and gas chromatography/mass spectrometry (GC/MS) 11. Sample pretreatment is an important step in analytical science for the isolation and enrichment of analytes from complex matrices.…”

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confidence: 99%

Drop‐to‐drop solvent microextraction coupled with gas chromatography/mass spectrometry for rapid determination of trimeprazine in urine and blood of rats: application to pharmacokinetic studies

Agrawal

2007

Rapid Comm Mass Spectrometry

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A simple and rapid method based on drop-to-drop solvent microextraction (DDSME) coupled with gas chromatography/mass spectrometry (GC/MS) has been successfully applied for the pharmacokinetic studies of trimeprazine in 8 microL of urine and blood samples of rats. Several factors that influenced the extraction efficiency of DDSME, such as selection of organic solvent, extraction time, exposure volume of organic phase, addition of salt and pH, were optimized. Linearity was obtained over the concentration ranges of 0.2-10, 0.25-7.0 and 0.5-6.0 microg/mL with correlation coefficients of 0.998, 0.996 and 0.993 in deionized water, urine and blood samples of rats, respectively. The limits of detection (LODs) of trimeprazine were 0.05, 0.06 and 0.1 microg/mL in deionized water, urine and blood samples. The concentrations of trimeprazine obtained in urine and blood samples of rats were 0.21-1.25 and 2.72-0.22 microg/mL, respectively, after a single intravenous administration of this drug. The enrichment factors and LOD values obtained by DDSME coupled to GC/MS were compared with those of hollow fiber liquid-phase microextraction (HF-LPME) combined with GC/MS. We believe that this novel approach can be very useful in clinical application since only one microdrop of biological samples was required to perform the pharmacokinetic studies from rats, so the sample pretreatments for animal experiments can be very easy too.

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confidence: 99%

Drop‐to‐drop solvent microextraction coupled with gas chromatography/mass spectrometry for rapid determination of trimeprazine in urine and blood of rats: application to pharmacokinetic studies

Agrawal

2007

Rapid Comm Mass Spectrometry

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“…Moreover, safety testing of trimeprazine in dogs has indicated that the drug has no end-organ toxicity (Dollery, 1991b). In rare cases, however, it can cause photosensitive dermatitis, drowsiness, abdominal discomfort and a reduction in the level of serum thyroid hormones, particularly thyroxine, in human subjects (Dollery, 1991b;Sauvage et al 1999).…”

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A comparative study on the effects of oral amiodarone and trimeprazine, twoin vitroretinyl ester hydrolase inhibitors, on the metabolic availability of vitamin A in rats

2005

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Amiodarone, an antiarrhythmic drug, and trimeprazine, an antipsychotic drug, are both in vitro inhibitors of retinyl ester hydrolase. To determine whether these agents have deleterious effects on aspects of vitamin A metabolism, Brown Norway rats (n 18) were treated at clinically equivalent doses once daily for 26 d with either oral drug. On day 27, a tolerance test was used to determine whether these agents interfered with vitamin absorption. During the first 8 d, the plasma retinol level declined in all animals. Between days 12 and 27, it rose to near pre-treatment concentrations in the control and trimeprazine groups and remained relatively constant at low levels (P,0·001) in the amiodarone group. The intestinal absorption of vitamin A was reduced (P,0·05) in the amiodarone group compared with the placebo and trimeprazine groups, which did not differ significantly from each other. At the end of the 4-week treatment period, hepatic retinyl ester hydrolase activity was lower in the drug-dosed rats (P¼ 0·06 for amiodarone) than in the controls. With regard to effects on liver reserves, drug treatment resulted in vitamin A depletion (P,0·019), and distinctive patterns of retinol and its esters were seen in response to dosing. In conclusion, amiodarone and trimeprazine have been shown to influence different aspects of retinoid metabolism, namely absorption, storage and transport. In clinical practice, the routine unmonitored use of these drugs and the suggestion that these agents be taken with meals are not recommended. Amiodarone-vitamin A interaction: Trimeprazine -vitamin A interaction: Retinyl ester hydrolaseVitamin A is a fat-soluble vitamin present in animal-based diets as retinyl esters (retinol esterified to fatty acids; Schindler et al. 1987). Once absorbed, liberated retinol is converted by the activity of acyltransferase back to esterified retinol, in which form vitamin A is targeted to the liver, its primary site of storage MacDonald & Ong, 1988). Central to vitamin A handling by the organism is the reversible, enzymatic conversion of retinyl esters to retinol (for reviews see Harrison, 1998).Retinyl ester-splitting enzymes are found ubiquitously, in many tissues, and it is generally assumed that their function, activity and regulation depend on the enzyme location. Whereas retinolliberating enzymes from pancreas and intestinal brush border are a pre-requisite for the full absorption of dietary vitamin A (Lombardo & Guy, 1980;Rigtrup et al. 1994), isoenzymes in eyes provide free retinol as an intermediate in rhodopsin regeneration (Tsin & Lam, 1986). In the liver, the central organ in maintaining body retinol homeostasis, the retinyl ester-converting enzymes are involved in the hydrolysis of vitamin A esters delivered to the hepatocytes via the receptor-mediated endocytosis of chylomicron remnants (Blomhoff et al. 1982) and the generation of free retinol from its storage form as esters (Goodman & Blaner, 1984). The liberated retinol acts as precursor for re-esterification for storage (Blaner et al. 198...

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In Vitro and in Vivo Study of the Antithyroid Side Effects of Trimeprazine

Cited by 2 publications

References 14 publications

Drop‐to‐drop solvent microextraction coupled with gas chromatography/mass spectrometry for rapid determination of trimeprazine in urine and blood of rats: application to pharmacokinetic studies

Drop‐to‐drop solvent microextraction coupled with gas chromatography/mass spectrometry for rapid determination of trimeprazine in urine and blood of rats: application to pharmacokinetic studies

A comparative study on the effects of oral amiodarone and trimeprazine, twoin vitroretinyl ester hydrolase inhibitors, on the metabolic availability of vitamin A in rats

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