In vivo and in vitro metabolism of dexamethasone in the camel

Katheeri, Nawal A. Al; Wasfi, I.A.; Lambert, Matthew; Albo, A. Giuliano; Nebbia, Carlo

doi:10.1016/j.tvjl.2005.06.003

Cited by 12 publications

(13 citation statements)

References 35 publications

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“…, 1998). We have previously shown that camel CYP2C and CYP3A subfamilies were both expressed in vitro (Al Katheeri et al. , 2006) in support of the previous findings (Raza et al.…”

Section: Discussionsupporting

confidence: 84%

“…The prominent P450 enzyme involved in the phase I biotransformation of meloxicam in humans is CYP 2C9, with a minor contribution of CYP 3A4 (Chesne et al, 1998). We have previously shown that camel CYP2C and CYP3A subfamilies were both expressed in vitro (Al Katheeri et al, 2006) in support of the previous findings (Raza et al, 1998). In the horse, however, although meloxicam metabolism is qualitatively similar to other species, its phase I biotransformation is not as extensive (Dumasia et al, 2006).…”

Section: Discussionsupporting

confidence: 59%

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The pharmacokinetics and metabolism of meloxicam in camels after intravenous administration

Wasfi¹,

Ali²,

Agha³

et al. 2011

Vet Pharm & Therapeutics

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The pharmacokinetics and metabolism of meloxicam was studied in camels (Camelus dromedarus) (n = 6) following intravenous (i.v.) administration of a dose of 0.6 mg·kg/body weight. The results obtained (mean ± SD) were as follows: the terminal elimination half-life (t(1/2β) ) was 40.2 ± 16.8 h and total body clearance (Cl(T) ) was 1.94 ± 0.66 mL·kg/h. The volume of distribution at steady state (V(SS)) was 92.8 ± 13.7 mL/kg. One metabolite of meloxicam was tentatively identified as methylhydroxy meloxicam. Meloxicam and metabolite were excreted unconjugated in urine. Meloxicam could be detected in plasma 10 days following i.v. administration in camels using a sensitive liquid chromatography tandem mass spectrometry (LC/MS/MS) method.

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“…, 1998). We have previously shown that camel CYP2C and CYP3A subfamilies were both expressed in vitro (Al Katheeri et al. , 2006) in support of the previous findings (Raza et al.…”

Section: Discussionsupporting

confidence: 84%

Section: Discussionsupporting

confidence: 59%

The pharmacokinetics and metabolism of meloxicam in camels after intravenous administration

Wasfi¹,

Ali²,

Agha³

et al. 2011

Vet Pharm & Therapeutics

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“…In ruminants, DEX is thought to be mainly hydroxylated at the 6-position and reduced at the 3-carbonyl group; then, both the parent drug and the metabolite undergo glucuronidation or sulphation (3,15). Recently, DEX, used for growth promoting purposes alone or in combination with other GPs, was shown to affect post-transcriptionally and to a various extent cattle cytochromes P450 (CYPs) (17,18).…”

Section: Introductionmentioning

confidence: 99%

Effects of Illicit Dexamethasone upon Hepatic Drug Metabolizing Enzymes and Related Transcription Factors mRNAs and Their Potential Use As Biomarkers in Cattle

Giantin¹,

Lopparelli²,

Zancanella³

et al. 2010

J. Agric. Food Chem.

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In cattle fattening, the illicit use of growth promoters (GPs) represents a major problem. The synthetic corticosteroid dexamethasone (DEX) is the GP mostly used, alone or in combination with other steroids or beta-agonists. Recently, GPs were shown to disrupt some cattle cytochromes P450 (CYPs) at the post-transcriptional level; therefore, the effects of two illicit protocols containing DEX (alone or together with 17beta-estradiol, 17betaE) upon main cattle liver drug metabolizing enzymes (DMEs) mRNAs and related transcription factors were investigated by quantitative real time RT-PCR. Eleven genes, out of the 18 considered, were significantly modulated by GPs. Corticosteroid-responsive genes did not respond univocally, whereas retinoic X receptor alpha (RXRalpha) and estrogen receptor alpha (ERalpha) were upregulated depending on the illicit protocol used. Nowadays, an increasing interest has been noticed toward the detection of biomarkers of response (BMRs) to be used in the screening of GPs misuse in cattle farming. In the present study, CYP2B6-like, CYP2E1, glutathione S-transferase A1- and sulfotransferase A1-like (GSTA1- and SULT1A1-like) mRNAs were significantly modulated regardless of the GP, the illicit protocol, and the animal breed, representing promising BMRs. The usefulness of these BMRs needs to be characterized more in depth.

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“…, 2005). In camels and cattle, metabolism of DEX occurs predominantly in the liver and includes (i) the reduction in the 3‐carbonyl group in ring A, mediated by hydroxysteroid dehydrogenases, and (ii) the hydroxylation at position 6 of the same ring (Al Katheeri et al. , 2006; Vanhaecke et al.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, the parent compound and its metabolites may be conjugated with both glucuronic acid and sulphate (Antignac et al. , 2002; Al Katheeri et al. , 2006).…”

Section: Discussionmentioning

confidence: 99%

Cytochrome P450 3A expression and function in liver and intestinal mucosa from dexamethasone‐treated sheep

Maté

Lifschitz

Sallovitz³

et al. 2011

Vet Pharm & Therapeutics

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The effects of repeated administrations of dexamethasone (DEX) (3 mg/kg/day by i.m. route for 7 days) on the gene expression profile of a cytochrome P450 (CYP) 3A28-like isoenzyme, on the expression of a CYP3A-immunoreactive protein and on CYP3A-dependent metabolic activities in sheep liver and small intestinal mucosa were evaluated in the current work. CYP 3A-dependent metabolic activities (erythromycin and triacetyl-oleandomycin N-demethylations) were assessed in microsomal fractions. The mRNA expression of CYP3A28-like, glucocorticoid receptor, constitutive androstane receptor, pregnane X receptor and retinoic X receptor alpha (RXRα) was determined by quantitative real-time PCR. The expression of a CYP3A-immunoreactive protein was measured by Western blot analyses. In the liver, DEX treatment increased CYP3A28-like mRNA levels (2.67-fold, P<0.01) and CYP3A apoprotein expression (1.34-fold, P<0.05) and stimulated CYP3A-dependent metabolism. High and significant correlation coefficients between CYP3A-dependent activities and CYP3A28-like gene (r=0.835-0.856, P<0.01) or protein (r=0.728-0.855, P<0.05) expression profiles were observed. Among the transcriptional factors, DEX only stimulated (2.1-fold, P<0.01) the mRNA expression of RXRα. In sheep small intestine, DEX caused a slight increment (34.6%, P<0.05) in erythromycin N-demethylase activity in the jejunal mucosa and a significant enhancement (P<0.05) of CYP3A apoprotein level in the duodenal mucosa.

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In vivo and in vitro metabolism of dexamethasone in the camel

Cited by 12 publications

References 35 publications

The pharmacokinetics and metabolism of meloxicam in camels after intravenous administration

The pharmacokinetics and metabolism of meloxicam in camels after intravenous administration

Effects of Illicit Dexamethasone upon Hepatic Drug Metabolizing Enzymes and Related Transcription Factors mRNAs and Their Potential Use As Biomarkers in Cattle

Cytochrome P450 3A expression and function in liver and intestinal mucosa from dexamethasone‐treated sheep

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