Pub Date : 2009-01-01DOI: 10.1515/DMDI.2009.24.2-4.331
U. Gröber
{"title":"Micronutrients: Metabolic Tuning - Prevention - Therapy","authors":"U. Gröber","doi":"10.1515/DMDI.2009.24.2-4.331","DOIUrl":"https://doi.org/10.1515/DMDI.2009.24.2-4.331","url":null,"abstract":"","PeriodicalId":77889,"journal":{"name":"Reviews on drug metabolism and drug interactions","volume":"24 1","pages":"331 - 331"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/DMDI.2009.24.2-4.331","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67184199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2005-01-01DOI: 10.1515/DMDI.2005.21.2.131
B. Yapici, I. Kaya, D. Şenol
Oligo-2-hydroxy-1-naphthaldehyde (OHNA) was synthesized by oxidative polycondensation using H2O2 (35%, aqueous solution), air O2 and NaOCl (34%, aqueous solution) by Kaya and Senol and the products were characterized by spectral techniques. Antimicrobial activities of the first and second fractions of OHNA were tested against Corynobacterium xerosis CCM 2824, Proteus vulgaris ATCC 6897, Staphylococcus epidermidis NRRL B-4877, S. aureus ATCC 6538, Enterobacter aerogenes ATCC 13048, Salmonella thyphimurium CCM 5445, Pseudomonas aeroginosa ATCC 27853, Escherichia coli ATCC 11230, E. coli ATCC 23998, Bacillus cereus ATCC 7064, B. cereus ATCC 99, B. subtilis ATCC 6633, Yersinia spp., Neisseria canis, Rhodotorula rubra, Kluyveromyces fragilis NRRL 2415, Saccharomyces cerevisiae ATCC 9763, S. ovarum, Debaryomyces hensenii, Hansenula anamola, Candida albicans, C. utilis, Aspergillus niger, A. fumigates, A. versicolor, A. flavus, A. parasiticus, Penicillium granulatum, P. chrysogenum, and P. herque. OHNA demonstrated antimicrobial activity against various bacteria and yeast, but did not affect filamentous fungi.
{"title":"Determination of the Antimicrobial Properties of Oligo-2-hydroxy-l-naphthaldehyde","authors":"B. Yapici, I. Kaya, D. Şenol","doi":"10.1515/DMDI.2005.21.2.131","DOIUrl":"https://doi.org/10.1515/DMDI.2005.21.2.131","url":null,"abstract":"Oligo-2-hydroxy-1-naphthaldehyde (OHNA) was synthesized by oxidative polycondensation using H2O2 (35%, aqueous solution), air O2 and NaOCl (34%, aqueous solution) by Kaya and Senol and the products were characterized by spectral techniques. Antimicrobial activities of the first and second fractions of OHNA were tested against Corynobacterium xerosis CCM 2824, Proteus vulgaris ATCC 6897, Staphylococcus epidermidis NRRL B-4877, S. aureus ATCC 6538, Enterobacter aerogenes ATCC 13048, Salmonella thyphimurium CCM 5445, Pseudomonas aeroginosa ATCC 27853, Escherichia coli ATCC 11230, E. coli ATCC 23998, Bacillus cereus ATCC 7064, B. cereus ATCC 99, B. subtilis ATCC 6633, Yersinia spp., Neisseria canis, Rhodotorula rubra, Kluyveromyces fragilis NRRL 2415, Saccharomyces cerevisiae ATCC 9763, S. ovarum, Debaryomyces hensenii, Hansenula anamola, Candida albicans, C. utilis, Aspergillus niger, A. fumigates, A. versicolor, A. flavus, A. parasiticus, Penicillium granulatum, P. chrysogenum, and P. herque. OHNA demonstrated antimicrobial activity against various bacteria and yeast, but did not affect filamentous fungi.","PeriodicalId":77889,"journal":{"name":"Reviews on drug metabolism and drug interactions","volume":"21 1","pages":"131 - 138"},"PeriodicalIF":0.0,"publicationDate":"2005-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/DMDI.2005.21.2.131","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67184603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-01-01DOI: 10.1515/DMDI.2001.18.3-4.209
E. Ershov, M. Bellaiche, V. Hanji, S. Soback, M. Gips, A. Shlosberg
The concomitant administration to broilers of ionophore coccidiostats and certain chemotherapeutic agents may cause deleterious interactions, with toxicosis and death as possible sequelae. In this study, co-administration of the ionophore monensin was not shown to alter blood levels of enrofloxacin or norfloxacin. In addition, exposure to lasalocid was not shown to change blood levels of enrofloxacin. However, norfloxacin + lasalocid co-administration induced aminopyrine N-demethylase (AD) activity by day 5 after the last administration of norfloxacin, and induced a rise of norfloxacin levels in the blood. This rise of blood norfloxacin levels after co-administration of norfloxacin + lasalocid implies that lower levels of norfloxacin could be administered in birds also receiving lasalocid.
{"title":"Interaction of Fluoroquinolones and Certain Ionophores in Broilers: Effect on Blood Levels and Hepatic Cytochrome P450 Monooxygenase Activity","authors":"E. Ershov, M. Bellaiche, V. Hanji, S. Soback, M. Gips, A. Shlosberg","doi":"10.1515/DMDI.2001.18.3-4.209","DOIUrl":"https://doi.org/10.1515/DMDI.2001.18.3-4.209","url":null,"abstract":"The concomitant administration to broilers of ionophore coccidiostats and certain chemotherapeutic agents may cause deleterious interactions, with toxicosis and death as possible sequelae. In this study, co-administration of the ionophore monensin was not shown to alter blood levels of enrofloxacin or norfloxacin. In addition, exposure to lasalocid was not shown to change blood levels of enrofloxacin. However, norfloxacin + lasalocid co-administration induced aminopyrine N-demethylase (AD) activity by day 5 after the last administration of norfloxacin, and induced a rise of norfloxacin levels in the blood. This rise of blood norfloxacin levels after co-administration of norfloxacin + lasalocid implies that lower levels of norfloxacin could be administered in birds also receiving lasalocid.","PeriodicalId":77889,"journal":{"name":"Reviews on drug metabolism and drug interactions","volume":"18 1","pages":"209 - 220"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/DMDI.2001.18.3-4.209","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67183911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-01-01DOI: 10.1515/DMDI.2001.18.3-4.251
P. Yeung, Jdz Feng, S. Buckley
The objective of this study was to systematically determine the pharmacokinetics and metabolism of diltiazem (DTZ) after a single i.v. dose, and after single and multiple oral (p.o.) doses. Four mongrel dogs (3 M, 1 F), aged 1-3 years, body weight 19-25 kg, were each given a single 30 mg dose of DTZ as a solution by i.v injection, the same dose orally from an immediate release tablet (Cardizem, Aventis Pharma, Canada, QC), and also t.i.d. for 10 doses. A 3-4 week washout period was allowed between each treatment. Blood samples (4 ml each) were obtained after each treatment from each animal via a cephalic vein at 0 (just before dosing), 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, and 12.0 h post dose. Urine samples were collected for 24 h. The plasma samples were immediately separated by centrifugation and stored at -20 degrees C until analysis. The results showed that the bioavailability after a single p.o. dose of DTZ was 26+/-24%. Following a single i.v. dose, DTZ declined bi-exponentially with a terminal half-life (t1/2) of 4.2+/-1.7 h. N-Monodesmethyl DTZ (M(A)), deacetyl DTZ (M1), and deacetyl N-monodesmethyl DTZ (M2) were the major metabolites. Contrary to the results observed in clinical studies, there were no increase of plasma concentrations of DTZ after repeated doses (accumulation factor R = 0.94+/-0.51). Plasma concentrations of M1 decreased following repeated oral doses, accompanying by an increase of plasma concentrations of M2, although these changes were not statistically significant (p >0.05). This study cautions the use of mongrel dogs for direct extrapolation to humans, particularly for chronic pharmacokinetics studies of DTZ.
{"title":"Effect of Administration Route and Length of Exposure on Pharmacokinetics and Metabolism of Diltiazem in Dogs","authors":"P. Yeung, Jdz Feng, S. Buckley","doi":"10.1515/DMDI.2001.18.3-4.251","DOIUrl":"https://doi.org/10.1515/DMDI.2001.18.3-4.251","url":null,"abstract":"The objective of this study was to systematically determine the pharmacokinetics and metabolism of diltiazem (DTZ) after a single i.v. dose, and after single and multiple oral (p.o.) doses. Four mongrel dogs (3 M, 1 F), aged 1-3 years, body weight 19-25 kg, were each given a single 30 mg dose of DTZ as a solution by i.v injection, the same dose orally from an immediate release tablet (Cardizem, Aventis Pharma, Canada, QC), and also t.i.d. for 10 doses. A 3-4 week washout period was allowed between each treatment. Blood samples (4 ml each) were obtained after each treatment from each animal via a cephalic vein at 0 (just before dosing), 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, and 12.0 h post dose. Urine samples were collected for 24 h. The plasma samples were immediately separated by centrifugation and stored at -20 degrees C until analysis. The results showed that the bioavailability after a single p.o. dose of DTZ was 26+/-24%. Following a single i.v. dose, DTZ declined bi-exponentially with a terminal half-life (t1/2) of 4.2+/-1.7 h. N-Monodesmethyl DTZ (M(A)), deacetyl DTZ (M1), and deacetyl N-monodesmethyl DTZ (M2) were the major metabolites. Contrary to the results observed in clinical studies, there were no increase of plasma concentrations of DTZ after repeated doses (accumulation factor R = 0.94+/-0.51). Plasma concentrations of M1 decreased following repeated oral doses, accompanying by an increase of plasma concentrations of M2, although these changes were not statistically significant (p >0.05). This study cautions the use of mongrel dogs for direct extrapolation to humans, particularly for chronic pharmacokinetics studies of DTZ.","PeriodicalId":77889,"journal":{"name":"Reviews on drug metabolism and drug interactions","volume":"18 1","pages":"251 - 262"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/DMDI.2001.18.3-4.251","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67184553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-01-01DOI: 10.1515/DMDI.2001.18.2.135
I. Mahmood
The objective of this study was to evaluate whether a priori knowledge of cytochrome P450 isozymes involved in drug metabolism coupled with Mahmood' and Balian's 'rule of exponents' can be helpful for the prediction of clearance in humans using animal data. The clearance of 27 randomly selected drugs metabolized by different isozymes were scaled up from the animal data (at least three animal species) obtained from the literature. Three methods were utilized to generate allometric equations to scale up the clearance values: (i) clearance vs body weight (simple allometry); (ii) product of the clearance and maximum life-span potential (MLP) vs body weight; and (iii) the product of clearance and brain weight vs body weight. The choice of one of the methods was based on the 'rule of exponents' as described by Mahmood and Balian. The results of this study indicate that the knowledge of a particular isozyme does not provide a guide for the failure or success of allometry for the prediction of clearance. There is no trend which indicates that the chances of accurate prediction of clearance for a given drug are comparatively higher or lower when they are metabolized by a particular isozyme.
{"title":"Interspecies Scaling: Is a priori Knowledge of Cytochrome P450 Isozymes Involved in Drug Metabolism Helpful in Prediction of Clearance in Humans from Animal Data?","authors":"I. Mahmood","doi":"10.1515/DMDI.2001.18.2.135","DOIUrl":"https://doi.org/10.1515/DMDI.2001.18.2.135","url":null,"abstract":"The objective of this study was to evaluate whether a priori knowledge of cytochrome P450 isozymes involved in drug metabolism coupled with Mahmood' and Balian's 'rule of exponents' can be helpful for the prediction of clearance in humans using animal data. The clearance of 27 randomly selected drugs metabolized by different isozymes were scaled up from the animal data (at least three animal species) obtained from the literature. Three methods were utilized to generate allometric equations to scale up the clearance values: (i) clearance vs body weight (simple allometry); (ii) product of the clearance and maximum life-span potential (MLP) vs body weight; and (iii) the product of clearance and brain weight vs body weight. The choice of one of the methods was based on the 'rule of exponents' as described by Mahmood and Balian. The results of this study indicate that the knowledge of a particular isozyme does not provide a guide for the failure or success of allometry for the prediction of clearance. There is no trend which indicates that the chances of accurate prediction of clearance for a given drug are comparatively higher or lower when they are metabolized by a particular isozyme.","PeriodicalId":77889,"journal":{"name":"Reviews on drug metabolism and drug interactions","volume":"18 1","pages":"135 - 148"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/DMDI.2001.18.2.135","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67183423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-01-01DOI: 10.1515/DMDI.2001.18.1.1
R. Cameron, G. Feuer
In this review we examine the modifying effect of specific drugs on apoptosis. Apoptosis is a type of cell death prevalent during many physiological and pathological conditions, consisting of several steps, namely, initiating stimuli, transduction pathways, effector mechanisms, nuclear fragmentation, and phagocytosis. Pharmacological substances such as glucocorticoids can either induce or inhibit the process of apoptosis in various cells depending on the type of drug and its concentration. Understanding the mechanisms of interaction of drugs with cells undergoing apoptosis could encourage novel therapeutic approaches to human diseases in which apoptosis has a critical role.
{"title":"The Effect of Drugs and Toxins on the Process of Apoptosis","authors":"R. Cameron, G. Feuer","doi":"10.1515/DMDI.2001.18.1.1","DOIUrl":"https://doi.org/10.1515/DMDI.2001.18.1.1","url":null,"abstract":"In this review we examine the modifying effect of specific drugs on apoptosis. Apoptosis is a type of cell death prevalent during many physiological and pathological conditions, consisting of several steps, namely, initiating stimuli, transduction pathways, effector mechanisms, nuclear fragmentation, and phagocytosis. Pharmacological substances such as glucocorticoids can either induce or inhibit the process of apoptosis in various cells depending on the type of drug and its concentration. Understanding the mechanisms of interaction of drugs with cells undergoing apoptosis could encourage novel therapeutic approaches to human diseases in which apoptosis has a critical role.","PeriodicalId":77889,"journal":{"name":"Reviews on drug metabolism and drug interactions","volume":"18 1","pages":"1 - 32"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/DMDI.2001.18.1.1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67183280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-01-01DOI: 10.1515/DMDI.2001.18.2.79
G. Steventon, S. Sturman, R. Waring, A. Williams
The role of xenobiotic metabolising enzymes (XMEs) in disease aetiology has been under investigation by numerous researchers around the world for the last two decades. The association of a number of defects in both phase I and phase II reactions with Parkinson's disease (PD) and motor neuron disease (MND) have been extensively studied. This review of the work of the group based initially at the University of Birmingham into the functional genomics of XMEs and neurodegenerative diseases has indicated that: 1. Sub-groups of patients with PD and MND can be identified with problems in xenobiotic metabolism by in vivo or in vitro methods. 2. 38-39% of the patients with MND/PD have a defect in the S-oxidation of the mucoactive drug, carbocysteine, by an unknown cytosolic oxidase(s). The odds risk ratio for the association of this defect with these diseases was calculated to be 10.21 for MND and 10.50 for PD. 3. Patients with PD appear to have an altered substrate specificity for monoamine oxidase B substrates in an in vitro platelet assay. 4. Patients with MND have an increased capacity to S-methylate aliphatic sulphydryl compounds in an in vivo challenge as well as an in vitro erythrocyte thiol methyltransferase assay. The results of over a decade of investigations into both PD and MND indicate that these are diseases with mutifactorial origins that encompass both genetic predisposition and environmental insult.
{"title":"A Review of Xenobiotic Metabolism Enzymes in Parkinson's Disease and Motor Neuron Disease","authors":"G. Steventon, S. Sturman, R. Waring, A. Williams","doi":"10.1515/DMDI.2001.18.2.79","DOIUrl":"https://doi.org/10.1515/DMDI.2001.18.2.79","url":null,"abstract":"The role of xenobiotic metabolising enzymes (XMEs) in disease aetiology has been under investigation by numerous researchers around the world for the last two decades. The association of a number of defects in both phase I and phase II reactions with Parkinson's disease (PD) and motor neuron disease (MND) have been extensively studied. This review of the work of the group based initially at the University of Birmingham into the functional genomics of XMEs and neurodegenerative diseases has indicated that: 1. Sub-groups of patients with PD and MND can be identified with problems in xenobiotic metabolism by in vivo or in vitro methods. 2. 38-39% of the patients with MND/PD have a defect in the S-oxidation of the mucoactive drug, carbocysteine, by an unknown cytosolic oxidase(s). The odds risk ratio for the association of this defect with these diseases was calculated to be 10.21 for MND and 10.50 for PD. 3. Patients with PD appear to have an altered substrate specificity for monoamine oxidase B substrates in an in vitro platelet assay. 4. Patients with MND have an increased capacity to S-methylate aliphatic sulphydryl compounds in an in vivo challenge as well as an in vitro erythrocyte thiol methyltransferase assay. The results of over a decade of investigations into both PD and MND indicate that these are diseases with mutifactorial origins that encompass both genetic predisposition and environmental insult.","PeriodicalId":77889,"journal":{"name":"Reviews on drug metabolism and drug interactions","volume":"18 1","pages":"79 - 98"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/DMDI.2001.18.2.79","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67183861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-01-01DOI: 10.1515/DMDI.2001.18.3-4.221
D.F.V. Lewis, Sandeep Modi, M. Dickins
The results of quantitative structure-activity relationship (QSAR) analyses are reported for structurally diverse series of chemicals which act as substrates or inhibitors for human hepatic microsomal cytochromes P450 (CYP). In particular, this study focuses on the major catalysts of drug metabolism in man, namely CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6 and CYP3A4. It is found that good correlations (with correlation coefficients ranging from R = 0.94 to 0.99) with P450 binding affinity (Km and K(D)) or competitive inhibition (Ki) values are obtained in each case, especially when consideration of hydrogen bonding parameters are included in the QSAR analysis, together with the number of pi-pi stacking interactions.
{"title":"Quantitative Structure-Activity Relationships (QSARs) Within Substrates of Human Cytochromes P450 Involved in Drug Metabolism","authors":"D.F.V. Lewis, Sandeep Modi, M. Dickins","doi":"10.1515/DMDI.2001.18.3-4.221","DOIUrl":"https://doi.org/10.1515/DMDI.2001.18.3-4.221","url":null,"abstract":"The results of quantitative structure-activity relationship (QSAR) analyses are reported for structurally diverse series of chemicals which act as substrates or inhibitors for human hepatic microsomal cytochromes P450 (CYP). In particular, this study focuses on the major catalysts of drug metabolism in man, namely CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6 and CYP3A4. It is found that good correlations (with correlation coefficients ranging from R = 0.94 to 0.99) with P450 binding affinity (Km and K(D)) or competitive inhibition (Ki) values are obtained in each case, especially when consideration of hydrogen bonding parameters are included in the QSAR analysis, together with the number of pi-pi stacking interactions.","PeriodicalId":77889,"journal":{"name":"Reviews on drug metabolism and drug interactions","volume":"18 1","pages":"221 - 242"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/DMDI.2001.18.3-4.221","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67184061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-01-01DOI: 10.1515/DMDI.2001.18.2.99
S. Zhou,, E. Chan
Interaction between the antioxidant ubidecarenone and the oral anticoagulant warfarin enantiomers was investigated in rats. The decreased hypoprothrombinemic response, assessed by means of percent changes of prothrombin complex activity and clotting factor VII activity, to warfarin, was observed following oral administration of 1.5 mg/kg racemic warfarin to rats during an 8-day oral regimen (10 mg/kg daily) of ubidecarenone. The antioxidant had no apparent effect on the in vitro rat serum protein binding of warfarin enantiomers. Treatment with ubidecarenone did not affect the absorption and distribution of the S- and R-enantiomers of warfarin, but produced a significant increase in the total serum clearance values of both R- and S-warfarin in rats. This effect was more pronounced with R-warfarin than with S-warfarin. The increased clearance values are attributable to acceleration of certain metabolic pathways and renal excretion of the warfarin enantiomers.
{"title":"Effect of Ubidecarenone on Warfarin Anticoagulation and Pharmacokinetics of Warfarin Enantiomers in Rats","authors":"S. Zhou,, E. Chan","doi":"10.1515/DMDI.2001.18.2.99","DOIUrl":"https://doi.org/10.1515/DMDI.2001.18.2.99","url":null,"abstract":"Interaction between the antioxidant ubidecarenone and the oral anticoagulant warfarin enantiomers was investigated in rats. The decreased hypoprothrombinemic response, assessed by means of percent changes of prothrombin complex activity and clotting factor VII activity, to warfarin, was observed following oral administration of 1.5 mg/kg racemic warfarin to rats during an 8-day oral regimen (10 mg/kg daily) of ubidecarenone. The antioxidant had no apparent effect on the in vitro rat serum protein binding of warfarin enantiomers. Treatment with ubidecarenone did not affect the absorption and distribution of the S- and R-enantiomers of warfarin, but produced a significant increase in the total serum clearance values of both R- and S-warfarin in rats. This effect was more pronounced with R-warfarin than with S-warfarin. The increased clearance values are attributable to acceleration of certain metabolic pathways and renal excretion of the warfarin enantiomers.","PeriodicalId":77889,"journal":{"name":"Reviews on drug metabolism and drug interactions","volume":"18 1","pages":"122 - 99"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/DMDI.2001.18.2.99","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67184025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2001-01-01DOI: 10.1515/DMDI.2001.18.2.123
R. Karwa, A. Shashank, D. Rambhau, D. Gopinath, D. Ravi
Rifampicin, an antitubercular agent, is a known metabolic inducer. Previous studies have suggested that rifampicin may interfere with the pharmacokinetics of oral zidovudine when the two drugs are co-administered. Circadian variations in the pharmacokinetics of rifampicin have been reported. We report here a circadian influence on the pharmacokinetics of zidovudine in the presence of rifampicin when administered orally in rabbits. Either zidovudine or zidovudine with rifampicin was administered orally at 10.00 or 22.00 h to 12 healthy rabbits in a randomized cross-over study. Serum zidovudine was estimated by HPLC. A significant (p <0.05) lowering of Cmax, (1/2), AUC(0-6h) and MRT was observed following zidovudine and rifampicin co-administration compared to zidovudine alone at 10.00 h. Accordingly clearance increased to a significant extent. However, such an interaction effect was masked following administration at 22.00 h. The time-dependent influence of rifampicin on the pharmacokinetics of zidovudine may be due to time-dependent changes in absorption and elimination of rifampicin, thus modifying its induction effect on the levels of UDP glucuronyl transferase and cytochrome P-450 content in liver which are responsible for metabolism of zidovudine.
{"title":"Time-Dependent Pharmacokinetic Interaction Between Zidovudine and Rifampicin Following Oral Administration of the Combination at 1000 and 2200 Hours","authors":"R. Karwa, A. Shashank, D. Rambhau, D. Gopinath, D. Ravi","doi":"10.1515/DMDI.2001.18.2.123","DOIUrl":"https://doi.org/10.1515/DMDI.2001.18.2.123","url":null,"abstract":"Rifampicin, an antitubercular agent, is a known metabolic inducer. Previous studies have suggested that rifampicin may interfere with the pharmacokinetics of oral zidovudine when the two drugs are co-administered. Circadian variations in the pharmacokinetics of rifampicin have been reported. We report here a circadian influence on the pharmacokinetics of zidovudine in the presence of rifampicin when administered orally in rabbits. Either zidovudine or zidovudine with rifampicin was administered orally at 10.00 or 22.00 h to 12 healthy rabbits in a randomized cross-over study. Serum zidovudine was estimated by HPLC. A significant (p <0.05) lowering of Cmax, (1/2), AUC(0-6h) and MRT was observed following zidovudine and rifampicin co-administration compared to zidovudine alone at 10.00 h. Accordingly clearance increased to a significant extent. However, such an interaction effect was masked following administration at 22.00 h. The time-dependent influence of rifampicin on the pharmacokinetics of zidovudine may be due to time-dependent changes in absorption and elimination of rifampicin, thus modifying its induction effect on the levels of UDP glucuronyl transferase and cytochrome P-450 content in liver which are responsible for metabolism of zidovudine.","PeriodicalId":77889,"journal":{"name":"Reviews on drug metabolism and drug interactions","volume":"18 1","pages":"123 - 134"},"PeriodicalIF":0.0,"publicationDate":"2001-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/DMDI.2001.18.2.123","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67183233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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