Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 180
Filter
1.
Gan To Kagaku Ryoho ; 36(11): 1857-61, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19920388

ABSTRACT

Individual variations in P-450 activity affect the in vivo pharmacokinetics as well as the efficacy and side effect of drugs. It is proposed that urinary glucaric acid (GA) level may indirectly represent P-450 activity and may therefore be an indicator of P- 450 activity in the clinical setting. However, no standard method has been developed so far. Metabolism of paclitaxel (PTX), an anticancer drug, is mediated by P-450. If P-450 activity could be predicted by measuring urinary GA level during PTX administration and individual blood PTX concentration could be inferred, urinary GA level would be a potent tool to predict the efficacy and side effects of the drug. We therefore measured the urinary GA levels of patients on antiepileptics that are suggested to induce P-450 and those of control subjects, to determine whether urinary GA level could be an indicator of P-450 activity. Then, we examined the relationship between urinary GA level and blood PTX concentration and looked into the possibility of predicting pharmacokinetics based on the relationship between urinary GA level and area under the blood concentration-time curve (AUC). The means+/-S. D. of urinary [(GA level)/(Cr level) x 10] levels of 16 patients on antiepileptic medication and 24 control subjects were 0. 98 mg/mL+/-0. 91 and 0. 19 mg/mL+/-0. 07, respectively. The urinary GA levels of patients on antiepileptic medication were significantly higher than those of control subjects. On the other hand, the relationship between AUC and urinary GA levels in eight patients on PTX showed that AUC tended to become large when urinary GA levels were low. The above results reveal that measuring urinary GA level by the easy and noninvasive way of urine collection would enable us to predict P-450 activity and infer blood PTX concentration.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacokinetics , Glucaric Acid/urine , Paclitaxel/pharmacokinetics , Aged , Anticonvulsants/pharmacokinetics , Antineoplastic Agents, Phytogenic/blood , Cytochrome P-450 Enzyme System/physiology , Female , Humans , Male , Middle Aged , Paclitaxel/blood
2.
Altern Med Rev ; 13(3): 205-15, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18950247

ABSTRACT

Modern instrumentation allows the measurement of organic acids in urine in their physiological concentration ranges. Eight of the compounds that are reported can serve as markers for specific toxicant exposure or detoxification challenges. Xylene exposure causes elevation of 2-methylhippurate, and orotic acid elevation reveals ammonia challenge that exceeds the capacity of the urea cycle. General hepatic detoxification stimulation by natural compounds, drugs, or xenobiotic compounds causes elevated levels of glucaric acid. Abnormalities of alpha-hydroxybutyrate, pyroglutamate, and sulfate can indicate up-regulated glutathione biosynthesis, impaired reformation of glutathione in the gamma-glutamyl cycle, and depleted total body glutathione status, respectively. Patterns of these compounds measured in a simple overnight urine specimen help to identify focal areas of clinical concern and monitor patient responses to detoxification interventions.


Subject(s)
Biomarkers/urine , Environmental Pollutants/pharmacokinetics , Inactivation, Metabolic , Benzoates/urine , Environmental Exposure , Glucaric Acid/urine , Hippurates/urine , Humans , Hydroxybutyrates/urine , Orotic Acid/urine , Pyrrolidonecarboxylic Acid/urine , Sulfates/urine
3.
Yakugaku Zasshi ; 128(1): 135-40, 2008 Jan.
Article in Japanese | MEDLINE | ID: mdl-18176065

ABSTRACT

We propose an improved method to measure urinary D-glucaric acid (GA), which might be of value as an indirect index of the activity of cytochrome P450 (CYP). This method was about 20 times more sensitive than existing methods. Beer's law was obeyed in the concentration range 5.5-66 ng ml(-1) for GA, with the effective molar absorptivity at 533 nm and the relative standard deviation being 9.1 x 10(5) dm(3) mol(-1) cm(-1) and 0.69% (n = 6), respectively. In addition, we introduced the correction value {GA/Cr ratio x10} of urinary GA by measuring urinary creatinine (Cr) at the same time. Based on the proposed method, the GA and Cr values in spot urines of healthy persons and cancer patients were subsequently measured and the correction values of both groups subjected to comparison. As a result, a statistically significant difference was recognized between the two groups.


Subject(s)
Cytochrome P-450 Enzyme System/metabolism , Glucaric Acid/urine , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Antineoplastic Agents/pharmacokinetics , Biomarkers/urine , Creatinine/urine , Drug Administration Schedule , Drug Monitoring , Humans , Liver/enzymology , Neoplasms/drug therapy , Neoplasms/urine
4.
J Pharmacol Sci ; 99(4): 323-8, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16314692

ABSTRACT

The action of some anticonvulsant drugs as the causal agents of attacks of acute porphyria has been widely documented in the literature. However, little attention has been paid to the effect of these drugs on the urinary excretion of porphyrins in non-porphyric subjects. In a sample of 82 epileptic patients treated with phenobarbital (n = 54), phenytoin (n = 64), carbamazepine (n = 33), and valproate (n = 8), the daily doses were expressed according to a drug score that would reflect the capacity of these drugs as enzymatic inducers when administered in polytherapy. A significantly increased urinary excretion of D-glucaric acid (DGA) and porphyrins was found in this group of patients (P<0.001), with coproporphyrin being the major fraction in all cases (>60%). Urinary DGA had a highly significant correlation with the drug score (r = 0.783, P<0.001); however, no significant correlations were found between the urinary porphyrins and DGA (r = 0.005) or the drug score (r = 0.053). Neither was any significant relationship found between the urinary porphyrins and the serum activity of 5'-nucleotidase (r = 0.066) or the presence of a cholestasis objectivized through the presence of the isoform of gamma-glutamyltransferase with beta-globulins electrophoretic mobility. However, in a group of 10 patients a significant correlation was found between the urinary excretion of porphyrins and beta-N-acetylhexosaminidase (r = 0.790, P<0.01). Therefore, it does not appear that the liver enzyme induction, or even a subclinical cholestasis, produced by the antiepileptic drugs administered to these patients may serve to explain the increase in the urinary excretion of porphyrins. A possible renal origin is proposed for the increase of urinary porphyrins in these cases.


Subject(s)
Anticonvulsants/adverse effects , Epilepsy/urine , Porphyrins/urine , Adult , Anticonvulsants/therapeutic use , Cholestasis/urine , Enzyme Induction/drug effects , Enzymes/urine , Epilepsy/drug therapy , Female , Glucaric Acid/urine , Humans , Male , Middle Aged , Porphyrias/urine , Pyridoxal Phosphate/pharmacology , Transaminases/blood
5.
J Clin Pharmacol ; 44(9): 974-80, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15317825

ABSTRACT

The effect of enzyme-inducing anticonvulsant drugs on the serum concentrations of lipoproteins has been widely studied. However, there is little agreement between the results with regard to the possible development of a lipoprotein profile related to an increased or decreased cardiovascular risk. It has been suggested that cholinesterase (ChE) could be induced by these drugs, something of undeniable interest as ChE appears to have a relation to the metabolism of lipoproteins. The serum activity of ChE was determined in a group of 90 adult epileptic patients (56 male and 34 female) treated with phenobarbital, phenytoin, and carbamazepine. The liver enzyme induction produced by these drugs was then evaluated by determining serum gamma-glutamyltranspherase activity and urinary excretion of D-glucaric acid. A significant increase of serum ChE (p < 0.005) was found in the group of patients compared to a control group (n = 49) with a similar distribution for age and sex. A significant correlation was found for both male and female patients between ChE and concentrations of triglycerides, phospholipids, cholesterol, low-density lipoprotein (LDL) phospholipids, LDL-cholesterol, and apolipoprotein B (p < 0.01). Similarly, in female patients, ChE had a significant correlation with the total cholesterol/high-density lipoprotein (HDL) cholesterol and LDL-cholesterol/HDL-cholesterol ratios (p < 0.01). The ChE/HDL-cholesterol relationship, which has been proposed as a marker for cardiovascular risk, presented significant correlations with the total cholesterol/HDL-cholesterol and LDL-cholesterol/HDL-cholesterol ratios in patients of both sexes (p < 0.001). In the case of epileptic patients treated with enzyme-inducing anticonvulsant drugs, there may be an association between the possible induction of ChE and the metabolism of lipoproteins containing apolipoprotein B.


Subject(s)
Anticonvulsants/adverse effects , Cholinesterases/biosynthesis , Epilepsy/enzymology , Lipoproteins/blood , Adolescent , Adult , Aged , Anticonvulsants/blood , Anticonvulsants/therapeutic use , Body Weight/physiology , Cholinesterases/blood , Enzyme Induction/drug effects , Epilepsy/drug therapy , Female , Glucaric Acid/blood , Glucaric Acid/urine , Humans , Male , Middle Aged , gamma-Glutamyltransferase/blood
6.
Toxicol Lett ; 144(1): 17-26, 2003 Sep 15.
Article in English | MEDLINE | ID: mdl-12919720

ABSTRACT

The polychlorinated biphenyls (PCBs) have been demonstrated to be inducers of hepatic microsomal enzymes and some of their effects such as hormonal imbalance, and alteration of lipid and porphyrin metabolism could be ascribed to this mechanism. For this reason, the urinary excretion of D-glucaric acid (DGA), an indirect indicator of enzymatic induction, was suggested as a biological marker of effect following exposure to PCBs. The aim of the present study was to investigate whether any inductive effects resulting from exposure to these compounds through ingestion of contaminated food could be detected early by measuring urinary DGA (U-DGA). U-DGA was measured in 73 subjects exposed to PCBs due to ingestion of PCB-contaminated food and levels ranged from 1.7 to 12.4 mmol/mol creatinine, with a mean value of 5.96 mmol/mol creatinine. These values were higher than those usually found in the general population. Sex and smoking habits did not affect U-DGA excretion, while age and alcohol intake were significantly correlated with U-DGA excretion, a finding in agreement with the results of other investigations. Neither total PCB blood concentration nor PCB chlorine content was significantly correlated with U-DGA excretion, and only the PCB 138 congener was weakly correlated with U-DGA levels. The results indicate that, for exposure to PCB resulting in blood concentrations up to 394 microg/l, no statistically significant effect of these persistent organochlorine compounds on human enzyme induction could be demonstrated, as measured by DGA urinary excretion.


Subject(s)
Glucaric Acid/urine , Polychlorinated Biphenyls/blood , Adolescent , Adult , Aged , Aged, 80 and over , Aging/metabolism , Alcohol Drinking/metabolism , Diet , Enzyme Induction/drug effects , Female , Humans , Male , Middle Aged , Regression Analysis , Smoking/metabolism
7.
Eur J Clin Pharmacol ; 58(9): 581-5, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12483450

ABSTRACT

OBJECTIVE: We investigated the effects of treatment with Saint John's wort (hypericum perforatum) extract on the urinary excretion of D-glucaric acid, 6beta-hydroxycortisol, and free cortisol in order to assess the effect of this extract on the activity of hepatic xenobiotic metabolizing enzymes. METHODS: Forty-eight healthy volunteers (25 male and 23 female) received a daily dose of 1800 mg hypericum extract for 14 days. Urinary excretion of D-glucaric acid, 6beta-hydroxycortisol, and free cortisol was measured in 24-h urine samples on the day preceding the initiation of hypericum treatment and after 14 days of treatment. D-Glucaric acid was measured enzymatically. Cortisol and 6beta-hydroxycortisol were quantified using high-performance liquid chromatography with ultraviolet detection. RESULTS: Urinary excretion of D-glucaric acid was unaffected after a 14-day treatment with Saint John's wort extract (26.7 micromol/day vs 27.7 micromol/day; 95% confidence interval of the difference: -1.9 to 3.8). The urinary excretion of 6beta-hydroxycortisol increased from a mean baseline value of 254 microg/day to 369 microg/day (P<0.0001) indicating induction of CYP3A. While the excretion of free cortisol was unaltered, the ratio of 6beta-hydroxycortisol to free cortisol changed significantly from 9.9 at baseline to 14.3 (95% confidence interval of the difference: 2.3-6.5) after Saint John's wort treatment. CONCLUSIONS: High-dose treatment with Saint John's wort extract induced CYP3A activity in healthy volunteers as evidenced by increased 6beta-hydroxycortisol excretion. This enzyme induction most likely contributes to the decreased bioavailability observed upon co-administration of various drugs with Saint John's wort extract. The D-glucuronic acid pathway appeared unaffected by Saint John's wort.


Subject(s)
Glucaric Acid/urine , Hydrocortisone/analogs & derivatives , Hydrocortisone/urine , Hypericum/chemistry , Adult , Aryl Hydrocarbon Hydroxylases/biosynthesis , Cytochrome P-450 CYP3A , Enzyme Induction , Female , Humans , Male , Oxidoreductases, N-Demethylating/biosynthesis , Plant Extracts/pharmacology
8.
Rev Neurol ; 35(8): 711-6, 2002.
Article in Spanish | MEDLINE | ID: mdl-12402220

ABSTRACT

A comparative study was carried out to examine urinary excretion of D glucaric acid (DGA), g glutamyltransferase (GGT) activity and the concentration of serum bilirubin as enzymatic induction markers in 89 adult patients (56 men and 33 women) who were receiving chronic treatment with phenobarbital, phenytoin, carbamazepine and valproate. As in most cases, these drugs were administered as a polytherapy; drugs doses were expressed in units/day, in accordance with a previously described system of scoring, which would reflect the induction capacity of the combination of drugs administered. We found a high prevalence of results that were above the upper reference limit for urinary DGA (93.2%) and serum GGT (80.6%). Bilirubin and its conjugate and non conjugate fractions were found to offer values that to a large extent matched those of the control group. The levels of the different biochemical variables presented significant correlations with the daily doses of the drugs administered, above all in the case of DGA (r= 0.773, p< 0.001). When we split the data according to sex, the correlations improved in men but were significantly worse in women. This fact could be due to a greater inter individual variability in the response to inducers of the phenobarbital type in female patients. Urinary DGA seems to be a better enzymatic induction marker than GGT and bilirubin and its serum fractions, the value of which appeared to be very limited in these cases. Separating GGT into its isoforms provided no further information of practical interest as regards the enzymatic activity as a whole.


Subject(s)
Anticonvulsants/pharmacology , Bilirubin/blood , Enzyme Induction/drug effects , Glucaric Acid/urine , gamma-Glutamyltransferase/blood , Adult , Anticonvulsants/therapeutic use , Biomarkers , Carbamazepine/pharmacology , Carbamazepine/therapeutic use , Epilepsy/drug therapy , Epilepsy/metabolism , Female , Humans , Male , Phenobarbital/pharmacology , Phenobarbital/therapeutic use , Phenytoin/pharmacology , Phenytoin/therapeutic use , Sex Factors , Valproic Acid/pharmacology , Valproic Acid/therapeutic use
9.
Clin Lab ; 48(7-8): 415-9, 2002.
Article in English | MEDLINE | ID: mdl-12146576

ABSTRACT

The purpose of this study was to investigate the relationship of changes in the enzyme-inducing anticonvulsant daily dosage (drug score) to variations in urinary D-glucaric acid excretion and gamma-glutamyltransferase and beta-glucuronidase serum activities. These biochemical determinations were carried out before and after a mean period of 5.0 years in 16 adult epileptic patients (8 men and 8 women) treated with phenobarbital, phenytoin and/or carbamazepine and with a good therapeutic compliance. A significant correlation between D-glucaric acid excretion and drug score was obtained (r=0.508, p<0.001). When the interindividual variation was diminished by assessing the changes of these variables in the same subjects, the correlation was better (r=0.836, p<0.001). However, a statistical significance was not attained between the gamma-glutamyltransferase or beta-glucuronidase and drug score changes. Therefore the urinary excretion of D-glucaric acid appears to be more sensitive to changes in anticonvulsant drug score than serum gamma-glutamyltransferase and beta-glucuronidase.


Subject(s)
Anticonvulsants/pharmacokinetics , Glucaric Acid/urine , Adult , Anticonvulsants/administration & dosage , Anticonvulsants/pharmacology , Carbamazepine/administration & dosage , Carbamazepine/pharmacokinetics , Carbamazepine/pharmacology , Dose-Response Relationship, Drug , Enzyme Induction/drug effects , Epilepsy/drug therapy , Female , Follow-Up Studies , Glucuronidase/blood , Glucuronidase/drug effects , Humans , Male , Middle Aged , Phenobarbital/administration & dosage , Phenobarbital/pharmacokinetics , Phenobarbital/pharmacology , Phenytoin/administration & dosage , Phenytoin/pharmacokinetics , Phenytoin/pharmacology , Sex Factors , gamma-Glutamyltransferase/blood , gamma-Glutamyltransferase/drug effects
10.
Mutat Res ; 390(3): 207-21, 1997 May 23.
Article in English | MEDLINE | ID: mdl-9186570

ABSTRACT

The ureic herbicide linuron [3-(3, 4-dichlorophenyl)-1-methoxy-1-methylurea] (CAS 330-55-2) was investigated for genotoxicity in a series of in vivo experiments. Since human exposure to herbicides is not only to the active principles, but also to all the chemicals present in the commercial formulation, we tested both pure and commercial linuron. Groups of rats were treated with gavage containing different doses of the herbicide (pure compound or commercial formulation) for 14 days. The doses were 150, 300 and 450 mg/kg b.wt. for the pure compound and 315.8, 631.6 and 947.4 mg/kg b.wt. for the commercial formulation (47.5% of linuron). Faeces and urine were collected at regular intervals. Urine specimens were analysed for their mutagenic metabolites, thioethers and D-glucaric acid content. Faeces extracts were tested for mutagenicity. Linuron's ability to cause DNA damage and cytogenetic effects was also investigated after treating groups of rats once with different doses of pure or commercial linuron. DNA single-strand breaks were assessed in rat liver using the alkaline elution technique and the single-cell microgel electrophoresis assay (SCGE: 'comet' assay), and in rat testes cells with the SCGE assay. Micronuclei induction was analysed in rat bone marrow erythrocytes. Results obtained were mainly negative when the excretion of mutagenic metabolites in urine and faeces of animals treated with the pure compound or with the linuron-based commercial formulation were monitored, whereas an increase in the urinary excretion of thioethers and D-glucaric acid was observed in rats treated with the commercial formulation. No increase in the frequency of micronucleated polychromatic erythrocytes was observed in the treated animals. However, linuron affected the viability of hepatocytes isolated from animals treated with higher doses. This cytotoxicity was accompanied by the induction of DNA single-strand breaks in the liver, as seen by the alkaline elution assay. The potential of pure linuron to induce in vivo DNA damage was confirmed with the microgel-electrophoresis technique ('comet' assay). Cytotoxicity was also seen in rat testes cells. However, no indication of DNA damage was visible.


Subject(s)
DNA Damage/drug effects , Herbicides/toxicity , Linuron/toxicity , Liver/drug effects , Administration, Oral , Animals , Feces/chemistry , Glucaric Acid/urine , Herbicides/administration & dosage , Herbicides/urine , Linuron/administration & dosage , Linuron/urine , Male , Micronuclei, Chromosome-Defective/drug effects , Micronucleus Tests , Mutagenicity Tests , Rats , Rats, Wistar , Salmonella typhimurium/drug effects , Salmonella typhimurium/genetics , Sulfides/urine , Testis/drug effects
11.
Int J Clin Pharmacol Ther ; 35(1): 14-8, 1997 Jan.
Article in English | MEDLINE | ID: mdl-9021436

ABSTRACT

Lansoprazole has been shown to induce cytochrome P450 1A (CYP1A) and CYP3A enzymes in human hepatocytes in vitro. In this study, urinary excretion of 6 beta-hydroxycortisol (6 beta-OHF) and D-glucaric acid (D-GA) were used to investigate the potential enzyme-inducing property of lansoprazole in vivo. Twenty-four healthy female volunteers (aged 19-35 years), who were taking oral contraceptives containing 0.03 mg ethinylestradiol and 0.15 mg levonorgestrel, were randomized in a cross-over design for the treatment with either 60 mg lansoprazole or placebo once daily during 2 subsequent menstrual cycles. Urinary excretion rates of 6 beta-OHF and D-GA were measured at days 14 and 21 of the menstrual cycles. Median pretreatment urinary excretion of 6 beta-OHF (212 and 218 micrograms/d, n = 24) and D-GA (20.1 and 32.7 mumol/d) did not significantly differ. Upon treatment median excretion of 6 beta-OHF was 255 and 241 micrograms/d (n = 23), and that of D-GA was 25.5 and 33.8 mumol/d, respectively. Thus, the relatively high dose of 60 mg/d lansoprazole failed to statistically significantly alter urinary excretion of 6 beta-OHF and D-GA, indicating that therapeutic doses of lansoprazole might not exhibit a phenobarbital-like induction in vivo.


Subject(s)
Enzyme Inhibitors/pharmacology , Glucaric Acid/urine , Hydrocortisone/analogs & derivatives , Omeprazole/analogs & derivatives , 2-Pyridinylmethylsulfinylbenzimidazoles , Adult , Contraceptives, Oral, Combined/pharmacology , Cross-Over Studies , Cytochrome P-450 Enzyme System/biosynthesis , Drug Interactions , Enzyme Induction , Estradiol Congeners/pharmacology , Ethinyl Estradiol/pharmacology , Female , Humans , Hydrocortisone/urine , Lansoprazole , Levonorgestrel/pharmacology , Omeprazole/pharmacology , Placebos , Progesterone Congeners/pharmacology
12.
Ann Rheum Dis ; 55(7): 478-81, 1996 Jul.
Article in English | MEDLINE | ID: mdl-8774168

ABSTRACT

OBJECTIVE: To examine if a correlation exists between cytochrome P-450 enzyme induction and disease activity in patients with rheumatoid arthritis (RA), measuring urinary excretion of D-glucaric acid (GA) as an index of phase II drug metabolism. METHODS: Patients with RA were treated with sulphasalazine, sodium aurothiomalate, or D-penicillamine in standard dose regimens, for 24 weeks. Patients with ankylosing spondylitis (AS) or non-inflammatory arthritis (NIA) acted as controls. The urinary GA:creatinine ratio was measured at 0, 12, and 24 weeks of treatment. RESULTS: Patients with RA had a slightly greater urinary GA:creatinine ratio than patients with AS or NIA at baseline; this increased during treatment with disease modifying antirheumatic drugs (DMARDs). Sulphasalazine treatment had a greater effect on GA excretion than sodium aurothiomalate or D-penicillamine; this difference was statistically significant between weeks 0 and 12 (p = 0.01). Gamma glutamyltranspeptidase concentration showed a weak correlation with GA excretion between weeks 0 and 12 (p = 0.03), but all other measurements of changes in disease activity (plasma viscosity, C reactive protein, platelets, and articular index) were found not to correlate with GA excretion between weeks 0-12 or 0-24. CONCLUSION: The increased excretion of GA in patients with RA receiving DMARD treatment is probably the result of an indirect effect on hepatic metabolism bearing no relationship to disease activity.


Subject(s)
Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/urine , Glucaric Acid/urine , Adult , Aged , Aged, 80 and over , Arthritis/urine , Arthritis, Rheumatoid/drug therapy , Biomarkers/urine , Creatinine/urine , Female , Humans , Male , Middle Aged , Severity of Illness Index , Spondylitis, Ankylosing/urine
13.
J Toxicol Environ Health ; 48(4): 349-58, 1996 Jul.
Article in English | MEDLINE | ID: mdl-8691506

ABSTRACT

The biological follow-up of subjects exposed to butyl glycol (BG) is generally accomplished using a standard blood count that is not sensitive enough to reveal early intoxication by this molecule. For this reason we have used an indirect test for evaluating the induction of hepatic enzymes, the measurement in urine of D-glucaric acid (DGA), which reflects the activity of the glucuronic acid enzyme pathway. This study was performed on 17 foundry workers exposed to BG emissions coming from paints used in cataphoresis. The airborne concentration of BG was less than 0.3 times the average limit exposure value. This study shows that BG emissions at low concentrations are able to increase the activity of the enzymes of the glucuronic acid pathway. DGA urinary excretion increased by 165% in winter (p < .01) and by 85% (p < .05) in summer when the doors are open and the BG concentration lower. DGA urinary excretion is significantly higher in smoking than in nonsmoking exposed workers. None of these workers had a perturbed blood count. This study shows that the urinary level of DGA provides a good test for the follow-up of exposure to BG in the electrophoresis painting plant, and that the exposed smoking workers seem to be more sensitive to BG exposure than do the nonsmokers. In conclusion, the measurement of urinary DGA might be considered as a useful test for the surveillance of subjects exposed to vapors containing BG.


Subject(s)
Ethylene Glycols/adverse effects , Glucaric Acid/urine , Occupational Exposure , Solvents/adverse effects , Adult , Air Pollution, Indoor , Enzyme Induction/drug effects , Gas Chromatography-Mass Spectrometry , Glucuronates/metabolism , Glucuronic Acid , Glucuronidase/antagonists & inhibitors , Humans , Liver/drug effects , Liver/enzymology , Male , Middle Aged , Paint , Seasons , Smoking/urine
14.
Environ Health Perspect ; 104 Suppl 3: 543-5, 1996 May.
Article in English | MEDLINE | ID: mdl-8781380

ABSTRACT

Biological monitoring of genotoxic hazard in the rubber industry was performed in 19 male workers and 20 age-matched controls in a local health unit in northern Italy. Peripheral blood lymphocytes were analyzed for the presence of DNA damage (single-cell microgel-electrophoresis, or comet assay) and for cytogenetic parameters (sister chromatid exchanges and micronuclei frequency, and proliferative rate index). The following bioassays were performed in urine samples: a) mutagenicity test and concentration of thioethers as markers of exposure, and b) excretion of D-glucaric acid and 6-beta-hydroxycortisol (related to 17-hydroxycorticosteroid excretion) as indicators of the inductive status of the microsomal enzyme system (phase-I). The exposed subjects showed statistically higher mean values of 17-hydroxycorticosteroids and micronuclei and lower values of 6-beta-hydroxycortisol than controls, when taking cigarette smoking into account. The comet assay showed higher values for migration distance in exposed subjects than controls, although the differences were not significant at a p-value of 0.05. These findings suggest that industrial exposure in the rubber processing industry may cause genetic damage and may modify the activity level of some enzymes; these results should be considered with caution due to the small number of subjects enrolled.


Subject(s)
Mutagens/analysis , Occupational Exposure , Adult , Biomarkers , Chromosome Aberrations , DNA Damage , Environmental Monitoring , Glucaric Acid/urine , Humans , Hydrocortisone/analogs & derivatives , Hydrocortisone/urine , Industry , Lymphocytes/drug effects , Male , Micronucleus Tests , Occupational Exposure/adverse effects , Rubber , Sister Chromatid Exchange/drug effects , Smoking/adverse effects , Sulfides/urine
15.
Chin Med J (Engl) ; 109(3): 201-5, 1996 Mar.
Article in English | MEDLINE | ID: mdl-8758309

ABSTRACT

OBJECTIVE: To determine the extent to which immaturity of hepatic microsomal enzyme activity might contribute to physiological jaundice. METHODS: Urinary excretion of D-glucaric acid, expressed in mumol glucaric acid/ mmol creatinine, was measured in 122 Chinese full-term healthy newborn babies during the first five days of life. Among the 122 babies, 22 were born by normal spontaneous delivery at the British Military Hospital and 100 were born by caesarean section at the Prince of Wales Hospital. RESULTS: In all babies the excretion of D-glucaric acid was highest on the first day of life and gradually decreased over the following 5 days. Five babies born by spontaneous delivery and six babies born by caesarean section developed jaundice during the study period. The excretion of D-glucaric acid in the jaundiced babies was significantly higher on the first two days than in the non-jaundiced babies. CONCLUSIONS: D-glucaric acid excretion was increased in jaundiced newborn babies in the first few days of life. This finding does not indicate less liver microsomal enzyme activity in the jaundiced babies compared to those non-jaundiced. On the contrary, it suggests that in idiopathic neonatal jaundice compensatory mechanism might operate from a very early stage to excrete a higher bilirubin load that might be present through haemolysis.


Subject(s)
Creatinine/urine , Glucaric Acid/urine , Jaundice, Neonatal/urine , Humans , Infant, Newborn , Liver/enzymology , Male
16.
Environ Health Perspect ; 104(1): 78-82, 1996 Jan.
Article in English | MEDLINE | ID: mdl-8834865

ABSTRACT

Biological monitoring of occupational hazards was performed in workers using cutting fluids containing N-nitrosodiethanolamine (NDELA). The study involved a group of 25 male subjects from some metal factories in central Italy who used cutting fluids with an NDELA content of > or = 5 mg/l (high-exposure group) and a group of 37 males exposed to cutting fluids with an NDELA content < 5 mg/l (low-exposure group). For comparison, we recruited a control group consisting of 37 subjects living in the same area. For all subjects, internal dose (urinary excretion of NDELA, mutagens, and thioethers), early biological effects (sister chromatid exchanges in blood peripheral lymphocytes), and urinary excretion of D-glucaric acid (DGA) as an endpoint product in the glucuronidation pathway were assessed. The results showed that only the workers using cutting fluids with NDELA concentrations of > or = 5 mg/l excreted trace amounts of NDELA in their urine. Urine excretion of mutagens was similar in the two exposure groups and in the controls. High-exposure subjects had a higher mean value of urinary thioethers than low-exposure and control subjects, but no differences were found in urinary DGA or lymphocyte sister chromatid exchange among the three groups. Smoking status increased the mean values of all the biomarkers, and coffee drinking was associated with urinary DGA excretion.


Subject(s)
Carcinogens/metabolism , Diethylnitrosamine/analogs & derivatives , Environmental Monitoring , Occupational Exposure , Adult , Carcinogens/adverse effects , Diethylnitrosamine/adverse effects , Diethylnitrosamine/metabolism , Diethylnitrosamine/urine , Glucaric Acid/urine , Humans , Male , Metallurgy , Middle Aged , Mutagens , Sister Chromatid Exchange , Sulfides/urine
17.
Clin Pharmacol Ther ; 58(3): 279-87, 1995 Sep.
Article in English | MEDLINE | ID: mdl-7554701

ABSTRACT

The effects of felbamate on the pharmacokinetics of phenobarbital and one of its main metabolites, parahydroxyphenobarbital, were assessed in a parallel-group, placebo-controlled, double-blind study, in 24 healthy volunteers. Pharmacokinetic parameters of phenobarbital and parahydroxyphenobarbital were determined from plasma and urine samples obtained after 28 days of daily administration of 100 mg phenobarbital and after a further 9 days of phenobarbital plus 2400 mg/day felbamate or placebo. Felbamate increased phenobarbital values for area under the plasma concentration-time curve from 0 to 24 hours and maximum concentration by 22% and 24%, respectively, whereas placebo had no effect. This increase was caused by a reduction in parahydroxylation of phenobarbital and possibly through effects on other metabolic pathways. Because felbamate inhibits the S-mephenytoin hydroxylase (CYP2C19) isozyme in vitro, it appears that phenobarbital hydroxylation is mediated in part by this isozyme.


Subject(s)
Anticonvulsants/pharmacology , Anticonvulsants/pharmacokinetics , Phenobarbital/pharmacokinetics , Propylene Glycols/pharmacology , Adult , Anticonvulsants/administration & dosage , Anticonvulsants/urine , Double-Blind Method , Drug Administration Schedule , Drug Interactions , Felbamate , Glucaric Acid/urine , Humans , Male , Phenobarbital/administration & dosage , Phenobarbital/analogs & derivatives , Phenobarbital/urine , Phenylcarbamates , Placebos
18.
G Ital Med Lav ; 17(1-6): 37-40, 1995.
Article in English | MEDLINE | ID: mdl-8940655

ABSTRACT

The evaluation of health status of workers exposed to a variety of chemicals is usually performed by means of several laboratory indices. Our aim is to review literature data in order to evaluate the influence of some lifestyle characteristics (alcohol intake) on these parameters. Since alcohol intake is responsible for a modification of some laboratory parameters in healthy workers, the medical surveillance of workers exposed to chemicals should include a careful evaluation of alcohol intake.


Subject(s)
Alcohol Drinking/adverse effects , Liver/drug effects , Occupational Exposure/adverse effects , Xenobiotics/adverse effects , Acyltransferases/analysis , Alcohol Drinking/metabolism , Biotransformation , Erythrocyte Volume/drug effects , Glucaric Acid/urine , Humans , Liver/metabolism , Liver Function Tests , Xenobiotics/pharmacokinetics
19.
Br J Clin Pharmacol ; 38(4): 376-80, 1994 Oct.
Article in English | MEDLINE | ID: mdl-7833230

ABSTRACT

The effects of the proton pump inhibitor lansoprazole on the bioavailability of a low-dose oral contraceptive (OC), containing 0.03 mg ethinyloestradiol (EE) and 0.15 mg levonorgestrel (LNG), were investigated. Twenty-four healthy females (aged 19-35 years; weight 60.6 +/- 7.1 kg) participated in a multiple-dose, placebo-controlled, randomized two-way cross-over study. All subjects received the OC over 2 full menstrual cycles from day 1 to day 21 separated by a drug-free interval of 7 days. Lansoprazole (60 mg day-1) or placebo was coadministered for 3 weeks each. Plasma concentrations of EE and LNG were determined by GC-MS. The 90% confidence intervals for ratios of Cmax and AUC after log transformation of both EE and LNG ranged between 91 and 111%, indicating that lansoprazole did not affect the bioavailability of EE and LNG.


PIP: The research reported in this paper assessed the effects of the proton pump inhibitor lansoprazole on the bioavailability of a low-dose oral contraceptive (OC) containing 0.03 mg ethinyl estradiol (EE) and 0.15 mg levonorgestrel (LNG). Blood plasma concentrations of lansoprazole, EE, LNG, and several hormones were measured following a two-way, cross-over study design. 24 German women in good health were used in this study. All subjects received physical examinations, complete laboratory work-ups, and were found normal. All women received the OC over two complete menstrual cycles from days 1 to 21, with the remaining 7 days being drug-free. 60 mg per day of lansoprazole or a placebo were given for 21 days with the OC. Plasma was assayed by capillary column gas chromatography with mass spectrometry. Urine was also collected and analyzed. The results showed that the 24 women did not experience any significant change or alteration in plasma EE and LNG levels.


Subject(s)
Contraceptives, Oral/pharmacokinetics , Omeprazole/analogs & derivatives , Proton Pump Inhibitors , 2-Pyridinylmethylsulfinylbenzimidazoles , Adult , Biological Availability , Chromatography, High Pressure Liquid , Contraceptives, Oral/blood , Cross-Over Studies , Estradiol/blood , Ethinyl Estradiol/blood , Ethinyl Estradiol/pharmacokinetics , Female , Follicle Stimulating Hormone/blood , Glucaric Acid/urine , Humans , Hydrocortisone/analogs & derivatives , Hydrocortisone/urine , Lansoprazole , Levonorgestrel/blood , Levonorgestrel/pharmacokinetics , Luteinizing Hormone/blood , Menstrual Cycle , Omeprazole/administration & dosage , Omeprazole/pharmacology , Progesterone/blood , Sex Hormone-Binding Globulin/metabolism , Therapeutic Equivalency
20.
Nihon Sanka Fujinka Gakkai Zasshi ; 46(7): 567-72, 1994 Jul.
Article in Japanese | MEDLINE | ID: mdl-8089594

ABSTRACT

It is known that urinary excretion of glucaric acid (GA) is an indirect index of hepatic P-450 microenzyme induction. We measured and analyzed urinary excretion of GA and plasma lipids in non-pregnant women, pregnant women and postpartum women. GA was measured by a new method for the inhibition of beta-glucuronidase activity and plasma lipids were measured by routine laboratory methods and we obtained the following results. 1. The concentration of urinary GA was correlated with that of urinary creatinine in pregnant women. 2. The urinary GA and plasma HDL-cholesterol did not change during the first of gestation, but steeply increased in the middle of gestation, and postpartum values were lower than at term. 3. Plasma total lipids, triglycerides, and total cholesterol continuously increased throughout gestation. 4. Plasma free fatty acids and lipid peroxide steeply increased in late in gestation. These results and several reports suggested that the change in GA in pregnant women reflected their own metabolism not fetal or placental metabolism. It seems that grasping and understanding their metabolism can make their disease clear.


Subject(s)
Glucaric Acid/urine , Pregnancy/metabolism , Cholesterol/blood , Cytochrome P-450 Enzyme System/metabolism , Fatty Acids, Nonesterified/blood , Female , Humans , Lipids/blood , Liver/enzymology , Triglycerides/blood
SELECTION OF CITATIONS
SEARCH DETAIL
...