Biomedical subjects

S L Huang

Publications and source records attributed to S L Huang.

At least 55 records · Page 3Linked to original sources

PubMed1999

Evidence for involvement of polymorphic CYP2C19 and 2C9 in the N-demethylation of sertraline in human liver microsomes.

AIMS: The present study was designed to define the kinetic behaviour of sertraline N-demethylation in human liver microsomes and to identify the isoforms of cytochrome P450 involved in this metabolic pathway. METHODS: The kinetics of the formation of N-demethylsertraline were determined in human liver microsomes from six genotyped CYP2C19 extensive (EM) and three poor metabolisers (PM). Selective inhibitors of and specific monoclonal antibodies to various cytochrome P450 isoforms were also employed. RESULTS: The kinetics of N-demethylsertraline formation in all EM liver microsomes were fitted by a two-enzyme Michaelis-Menten equation, whereas the kinetics in all PM liver microsomes were best described by a single-enzyme Michaelis-Menten equation similar to the low-affinity component found in EM microsomes. Mean apparent Km values for the high-and low-affinity components were 1.9 and 88 microm and V max values were 33 and 554 pmol min-1 mg-1 protein, respectively, in the EM liver microsomes. Omeprazole (a CYP2C19 substrate) at high concentrations and sulphaphenazole (a selective inhibitor of CYP2C9) substantially inhibited N-demethylsertraline formation. Of five monoclonal antibodies to various cytochrome P450 forms tested, only anti-CYP2C8/9/19 had any inhibitory effect on this reaction. The inhibition of sertraline N-demethylation by anti-CYP2C8/9/19 was greater in EM livers than in PM livers at both low and high substrate concentrations. However, anti-CYP2C8/9/19 did not abolish the formation of N-demethylsertraline in the microsomes from any of the livers. CONCLUSIONS: The polymorphic enzyme CYP2C19 catalyses the high-affinity N-demethylation of sertraline, while CYP2C9 is one of the low-affinity components of this metabolic pathway.

Antibodies, Monoclonal↗

PubMed1999

Association between body mass index and allergy in teenage girls in Taiwan.

BACKGROUND: The prevalence of atopy and asthma is affected by age, sex and lifestyle factors. Obesity was reported to be a risk factor for asthmatic symptoms in children and adults. OBJECTIVE: To examine the relation between body mass index (BMI) and the prevalence of atopy, rhinitis, wheezing and bronchial responsiveness in adolescents. METHODS: BMI (kg/m2), skin-prick test, bronchial hyperresponsiveness (BHR) to methacholine, and self-reported rhinitis and airway symptoms were assessed in a cross-sectional survey in 1459 eighth-grade students (age 13.2 to 15.5, mean 13.6 years) of seven junior high schools in northern Taiwan. RESULTS: The prevalence of atopy was 42% in boys and 27% in girls. The study population was grouped into quintiles of BMI by sex. Girls in the highest BMI quintile had higher prevalence of atopy and rhinitis symptoms. Compared with the middle three quintiles, they had increased risk of atopy in multivariate analyses adjusted for area of living, sibling number, parent education level and family history of asthma (odds ratio = 1.77, 95% confidence interval = 1.15-2.73). Girls with the lowest BMI quintile had lower prevalence of BHR and wheezing. Compared with the middle three quintiles, they had reduced risk of BHR in multivariate analyses adjusted for area of living, atopy, family history of asthma, and baseline pulmonary function (odds ratio = 0.40, 95% confidence interval = 0.20-0.81). No association between BMI and atopy or BHR was seen in boys. CONCLUSION: BMI was a significant predictor of atopy, allergic symptoms and BHR in teenage girls.

Adult↗

PubMed1999

Modulating influence of cytochrome P-450 MspI polymorphism on serum liver function profiles in coke oven workers.

OBJECTIVES: It was reported previously that topside oven workers with heavy exposure to coke oven emissions had increased serum activities of hepatic aminotransferase in one coke oven plant. This study was conducted to investigate the modifying effect of CYP1A1 MspI polymorphism on liver function profiles in coke oven workers. METHODS: 88 coke oven workers from a large steel company in Taiwan were studied in 1995-6. Exposure was categorised by work area: topside oven workers and sideoven workers. Liver function profiles including serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), r-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), and total bilirubin (BIL) were examined in the morning after personal exposure measurements. The MspI polymorphism was determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). RESULTS: Five of 23 (22%) topside oven workers and seven of 65 (11%) sideoven workers had the CYP1A1 MspI homozygous variant genotype. With sideoven workers with the combined wild type and heterozygous variant as the reference group in multiple regression models, it was found that topside oven workers with the combined traits had mean AST and ALT activities that were 21% and 46% higher (95% confidence interval (95% CI) 4% to 42% and 12% to 91%, respectively) than the reference group after adjusting for appropriate confounders. Also, topside oven workers with the homozygous variant trait had mean AST, ALT, and GGT activities that were 59%, 68%, and 157% higher (95% CI 21% to 109%, 6% to 168%, and 39% to 374%, respectively) than the reference group. The prevalence of an abnormal hepatocellular pattern (AST > 37 IU/l or ALT > 39 IU/l) was more common in the topside oven workers with the homozygous variant than in the sideoven workers with the other combined genotypes (adjusted odds ratio 9.9, 95% CI 1.2 to 82.3) after adjusting for appropriate confounders. CONCLUSIONS: The CYP1A1 MspI polymorphism may modify the biotransformation of coke oven emissions, which results in hepatocellular damage in coke oven workers.

Adult↗

PubMed1999

Climate, traffic-related air pollutants, and asthma prevalence in middle-school children in taiwan.

This study compared the prevalence of asthma with climate and air pollutant data to determine the relationship between asthma prevalence and these factors. We conducted a nationwide survey of respiratory illness and symptoms in middle-school students in Taiwan. Lifetime prevalences of physician-diagnosed asthma and of typical symptoms of asthma were compared to air monitoring station data for temperature, relative humidity, sulfur dioxide, nitrogen oxides, ozone, carbon monoxide, and particulate matter with aerodynamic diameter [less than/equal to] 10 microm (PM(10)). A total of 331,686 nonsmoking children attended schools located within 2 km of 55 stations. Asthma prevalence rates adjusted for age, history of atopic eczema, and parental education were associated with nonsummer (June-August) temperature, winter (January-March) humidity, and traffic-related air pollution, especially carbon monoxide and nitrogen oxides, for both girls and boys. Nonsummer temperature, winter humidity, and traffic-related air pollution, especially carbon monoxide and nitrogen oxides, were positively associated with the prevalence of asthma in middle-school students in Taiwan.

Adolescent↗

PubMed1999

Target selectivity of MAPK phosphorothioate antisense ODN on p42/p44, p38 MAPK, and JNK protein expression and its inhibitory effect on VSMC DNA synthesis.

AIM: To analyze the target selective and sequence-specific inhibitory effect of mitogen-activated protein kinase (MAPK) phosphorothioate antisense oligodeoxynucleotides (ODN) on p42/p44, p38 MAPK, c-jun NH2-terminal protein kinases (JNK) protein expression, and DNA synthesis in vascular smooth muscle cell (VSMC). METHODS: Using a phosphorothioate-protected 17-mer antisense MAPK ODN directed against the initiation of translation sites of the p42/p44 MAPK isoforms by liposomal transfection to deplete cultured rat, rabbit, and fetal calf VSMC MAP kinases. The 17-mer sense and random sequence MAPK ODN were used as controls. After liposomal transfection, cells were exposed to 20% serum for 24 h, and then harvested in lysis buffer. P42/p44, p38 MAPK, and p46/p58 JNK protein expression were measured by Western blot. DNA synthesis was measured by [3H]thymidine incorporation. RESULTS: Treatment with MAPK antisense ODN (0.1-0.8 mumol.L-1) for 48 h reduced phosphored p42/p44 MAPK protein expression but without effect on p38 MAPK and JNK expression, and inhibited cultured rat, rabbit, and fetal calf VSMC [3H]thymidine incorporation stimulated by 20% serum in a concentration-dependent manner. CONCLUSION: The MAPK antisense ODN target-selectively and sequence-specifically reduces the p42/p44 MAPK protein expression and concentration-dependently inhibits proliferation of rat, rabbit and fetal calf VSMC.

Animals↗

PubMed1999

Inhibition of platelet aggregation by bovine endocardial apyrase.

AIM: To study the anti-aggregatory effect of bovine endocardial endothelial cell (EEC)-associated apyrase. METHODS: Cultured bovine EEC was used. Adenosine diphosphate (ADP) was analyzed by reversed phase HPLC, and rabbit platelet aggregation was measured turbimetrically. RESULTS: Incubation of EEC with ADP 500 mumol.L-1 resulted in a progressive decrease in ADP concentration, which was paralleled by the decrease in platelet aggregating potential of the unmetabolized ADP. In the presence of aspirin (Asp 1 mmol.L-1)-treated EEC 1 x 10(9) cells.L-1, the aggregation of Asp (1 mmol.L-1) and methylene blue (10 mumol.L-1)-treated platelets in response to thrombin 500 U.L-1 and platelet activating factor (PAF 1 nmol.L-1) was markedly inhibited and was reversible, which was very similar to that in apyrase-treated platelets. The supernatants of EEC had no effect on platelet aggregation. EEC inhibited ADP (5 mumol.L-1)-induced platelet aggregation, but failed to inhibit adenosine 5'-O-(2-thiodiphosphate) (ADP-beta-S, an unmetabolizable structural analog of ADP, 15 mumol.L-1)-induced platelet aggregation. CONCLUSION: ADP hydrolysis by EEC-associated apyrase is a major anti-thrombotic mechanism of bovine EEC.

Adenosine Diphosphate↗

PubMed1999

Inhibitory effect of MAP kinase antisense oligonucleotide on angiotensin II-induced c-myc gene expression and proliferation of rat cardiac fibroblast.

AIM: To investigate the inhibitory effect of down-regulating mitogen activated protein kinase (MAPK) on c-myc gene expression and further on cardiac fibroblast proliferation. METHODS: Cultured neonatal rat cardiac fibroblasts was pretreated with a phosphorothioate-protected 17-mer antisense MAPK oligodeoxynucleotide (ODN) directed against the initiation of translation sites of the p42 and p44 MAPK isoforms by liposomal transfection. A 17-mer sense and mismatch sequence MAPK ODN were used as controls. After liposomal transfecting, cells were exposed to angiotensin II (Ang II) 10 nmol.L-1 for 5 min and then harvested in lysis buffer. MAPK activity was measured by Western blot and P-81 phosphocellulose filter paper method by using [gamma-32P]ATP and myelin basic protein as substrates. c-myc mRNA expression stimulated by Ang II for 30 min was measured by Northern blot. DNA synthesis and collagen protein synthesis induced by Ang II for 24 h were measured by [3H]thymidine incorporation and [3H]Proline incorporation, respectively. RESULTS: Antisense ODN 0.2 mumol.L-1 reduced Ang II-induced MAPK activities by 72%, MAPK protein expression by 80%, and suppressed c-myc mRNA expression by 97%, respectively. [3H]thymidine incorporation and [3H]proline incorporation in Ang II-induced cardiac fibroblast were inhibited by 59% and 58%, respectively. CONCLUSION: A 17-mer MAPK antisense oligonucleotide directed againsts the initiation of translation sites of MAPK could specifically inhibit Ang II-stimulated cultured neonatal rat cardiac fibroblast proliferation through down-regulating MAPK activity and further depleting c-myc mRNA expression.

Angiotensin II↗

PubMed1999

[Inhibitory effects of antisense oligonucleotides targeting mitogen-activated protein kinase (MAPK) mRNA on neonatal rat cardiac fibroblast proliferation induced by Ang II and EGF].

In the present study, the antisense oligodeoxynucleotide (ODN) approach was used to investigate whether mitogen-activated protein kinase (MAPK) is necessary for the proliferation response in neonatal rat cardiac fibroblast (FB) induced by angiotensin II (AngII) or epidermal growth factor (EGF), the proximal cytosolic signal transduction pathways which are quite different processes. A phosphorothioate-protected 17-mer directed against the initiation of translation sites P42 MAPK mRNA was introduced into FB by liposomal transfection. The results showed that (1) after a 24 h treatment with AngII or EGF (all 10(-8) mol/L), the FB numbers were increased by 39% and 68%, while the rate of DNA synthesis increased by 60% and 102%, respectively. (2) Following 5 min or 10 min stimulation with AngII or EGF, MAPK activity ([gamma-32P] ATP incorporation) increased by 202% and 305%, and phospho-MAPK protein content increased by 545% and 646% correspondingly. (3) As compared with lipofectin + AngII/EGF control, after pretreatment with MAPK antisense ODN, the MAPK protein expression was inhibited significantly; the rate of DNA synthesis of FB induced by AngII or EGF was reduced by 53% and 46%, cell numbers by 38% and 44%, respectively. Meanwhile, MAPK activity was decreased by 74.2% and 65.9%, phospho-MAPK protein content by 85% and 90%. The sense or random ODN has not much effect on them. Consequently, it can be concluded that (1) MAPK activity is essential in the event of involving FB proliferation response reduced by AngII and EGF, and (2) FB proliferation response could be inhibited by the MAPK antisense ODN through depletion of MAPK.

Angiotensin II↗

PubMed1999

Characteristics of apyrase (EC 3.6.1.5) on cultured bovine endocardial endothelial cells.

Apyrase activities in some tissues and cells, such as peripheral vascular endothelial cells, have been reported, but these in endocardium endothelial cells have not been reported. The present study was to characterise the properties of bovine endocardium endothelial cells (BEEC)-associated apyrase. Apyrase activity was assayed by inorganic phosphate release, which could be inhibited concentration-dependently by NaN3, an apyrase inhibitor. NaF (20 mmol/L), another inhibitor of apyrase, also markedly inhibited the activity. EDTA or EGTA (1 mmol/L) could also inhibit the activity completely. However, the inhibitor for Na+/K(+)-ATPase, ouabain (3 mmol/L) did not affect the enzyme activity. BEEC apyrase activity was dependent on divalent cations (Ca2+ or Mg2+) and pH value.

Animals↗

PubMed1998

New diterpenes from the heartwood of Chamaecyparis obtusa var. formosana.

An abietane diterpene, 11,14-dihydroxy-8,11,13-abietatrien-7-one (1); a seco-abietane diterpene, obtuanhydride (2); and an isopimarane diterpene, 18,19-O-isopropylidene-18, 19-dihydroxyisopimara-8(14),15-diene (3) were isolated from the heartwood of Chamaecyparis obtusa var. formosana. The structures of these new compounds were elucidated by spectroscopic methods.

Abietanes↗

PubMed1998

Subcellular phototoxicity of 5-aminolaevulinic acid (ALA).

BACKGROUND AND OBJECTIVE: 5-aminolaevulinic acid (ALA) is a new, promising photosensitizer for PDT of cancer. Subcellular toxicity induced by ALA and light exposure in single cells was studied to elucidate the mechanism of cell damage. STUDY DESIGN/MATERIALS AND METHODS: CPAE, PTK2, and rat neonatal myocardial cells treated with ALA were examined for localization using fluorescence microscopy and for subcellular phototoxicity using 630 nm laser microbeam irradiation of specific subcellular regions. RESULTS: In CPAE and PTK2 cells, a large amount of fluorescence was detected in the peri-nuclear cytoplasm. In rat neonatal myocardial cells, the sensitizer selectively localized in the large mitochondria. In both cell types, there was little phototoxicity when the peripheral cytoplasmic region was exposed, as compared to considerable phototoxicity with exposure of either the perinuclear or nuclear regions. CONCLUSION: Both the CPAE and PTK2 cells demonstrated that the nucleus followed by the perinuclear cytoplasm are the most sensitive cell areas with no sensitivity in the peripheral cytoplasm.

Aminolevulinic Acid↗

PubMed1998

Four new sesquiterpenes from Petasites formosanus.

Four new eremophilane-type sesquiterpenes, petasones A (1) and B (2), S-petasitin (3), and petasinol (4), were isolated from the aerial parts of Petasites formosanus. Their structures were elucidated by spectroscopic and chemical methods as 3alpha-[(Z)-3-methylsulfinylacryloxy]eremophila-7(11), 9-dien-8-one; 3alpha-[(E)-3-methylsulfinylacryloxy]eremophila-7(11), 9-dien-8-one; 3alpha-[(Z)-3-methylthioacryloxy]-11-hydroxyeremophila -6, 9-dien-8-one; and 3alpha-[(E)-3-methylsulfinylacryloxy]-8beta-hydroxy eremophila-9, 11-diene, respectively.

Carbohydrate Sequence↗

PubMed1998

The induction effect of rifampicin on activity of mephenytoin 4'-hydroxylase related to M1 mutation of CYP2C19 and gene dose.

AIMS: To determine the induction effect of rifampicin on the activity of 4'-hydroxylase in poor metabolizers (PMs) with m1 mutation of S-mephenytoin 4'-hydroxylation and the relationship of the effect with gene dose. METHODS: Seven extensive metabolizers (EMs) of S-mephenytoin 4'-hydroxylation and five PMs with m1 mutation were chosen to take rifampicin 300 mg day(-1) orally for 22 days. Prior to and after rifampicin treatment, each subject was given racemic mephenytoin 100 mg. The 4'-hydroxymephenytoin (4'-OH-MP) excreted in the 0-24 h urine and mephenytoin S/R ratio in the 0-8 h urine were determined by h.p.l.c. and GC, respectively. RESULTS: In all EMs, the excretion of 4'-OH-MP in the 0-24 h urine was increased by 146.4 +/- 17.9%, 0-8 h urinary mephenytoin S/R ratio was decreased by 77.3 +/- 8.8%, the percentage increase in the 0-24 h excretion of 4'-OH-MP in those CYP2C19 homozygous (wt/wt) was greater than that in those heterozygous (wt/m1 and wt/m2) (203.9 +/- 42.5% vs 69.6 +/- 4.1%). 0-8 h urinary mephenytoin S/R ratio of those PMs with m1 mutation was decreased by 9.6%, the amount of 4'-OH-MP excreted in the 0-24 h urine was increased by 80.1 +/- 48.0%. CONCLUSIONS: The activity of 4'-hydroxylase of PMs with m1 mutation of S-mephenytoin 4'-hydroxylation can be induced by rifampicin and the inducing effect of rifampicin on 4'-hydroxylase is gene dependent.

Adult↗

PubMed1998

Selective induction of apoptosis of NB4 cells from G2+M phase by sodium arsenite at lower doses.

Apoptosis of NB4 cells induced by sodium arsenite and arsenate was studied using flow cytometry and DNA gel electrophoresis in order to investigate their effects on cell cycle and determine the relationship between apoptosis and cell cycle. In this study, we found that: 1) at low doses, sodium arsenite selectively induced apoptosis of NB4 cells in G2+M phase of cell cycle after its being arrested in G2 phase. With increment of the cells blocked in G2 phase, dUTP-specifically labeling cells in G2+M phase increased without concomitant increment of dUTP-labeling cells in other two phases of cell cycle; 2) at high doses, extensive apoptosis was induced in NB4 cells from all phases of cell cycle without cell cycle preference and cell cycle blockade; 3) sodium arsenite-induced apoptosis of NB4 cells occurred in the presence of bcl-2 expression as the unapoptotic cells; 4) sodium arsenite with As3+ induced apoptosis of NB4 cells more strongly than sodium arsenate with As5+ did although both of them affected NB4 cells in the same pattern. These results not only suggested that both arsenite and arsenate induced apoptosis of NB4 cells through 2 different mechanisms--at low doses, arsenical might directly induce apoptosis through regulation of cell cycle checkpoint, while at high doses they might directly induce it, but also indicated that bcl-2 might not play an important role in arsenite or arsenate-induced apoptosis of NB4 cells, whereas chemical valence of As in a compound might be related to efficiency in arsenical induction of apoptosis.

Apoptosis↗

PubMed1998

Adverse effect of air pollution on respiratory health of primary school children in Taiwan.

This study is a part of the Study On Air Pollution and Health In Taiwan (SOAP&HIT), an ongoing research project involving cooperation of several universities in Taiwan. In this study, the objective was to evaluate the effects of ambient air pollution on respiratory symptoms and diseases of school children, in addition to considering indoor air pollution. Six communities were selected: one community located in a rural area (Taihsi), two in urban areas (Keelung and Sanchung), and the other three in petrochemical industrial areas (Toufen, Jenwu, and Linyuan). We sampled 5,072 primary school students in six communities from the main study population of SOAP&HIT. Respiratory health was assessed by evaluation of the children's respiratory symptoms and diseases using a parent-completed questionnaire. Data were analyzed using logistic regression analysis to compute odds ratios of adverse effect. The school children in the urban communities had significantly more respiratory symptoms (day or night cough, chronic cough, shortness of breath, and nasal symptoms) and diseases (sinusitis, wheezing or asthma, allergic rhinitis, and bronchitis) when compared with those living in the rural community. However, only nasal symptoms of children living in the petrochemical communities were more prevalent than in those living in the rural community. Although the association with ambient air pollution is suggestive, the cross-sectional study cannot confirm a causal relationship; thus further studies are needed.

Air Pollution↗

PubMed1998

Aneurysmal subarachnoid hemorrhage in Taiwan.

In 1993, the annual report about prospective survey and registry of stroke revealed there were 439 cases of ruptured intracranial aneurysms in Taiwan area. Thirty-two of them had multiple aneurysms; therefore, totally 476 aneurysms occurred in these cases. The anatomic distribution of these aneurysms were as the following: internal carotid artery-posterior communicating artery 32%, anterior communicating artery 30%, middle cerebral artery 18%, carotid bifurcation 6%, anterior cerebral artery 4%, carotid-ophthalmic artery 2%, intracavernous carotid artery 2%, and vertebrobasilar system 6%. 364 cases received surgical or interventional treatment, which 88% was clipping procedure, 8% was interventional procedure with coil, and 4% was wrapping. The surgical mortality was 13%.

Humans↗

PubMed1998

Use of caffeine as a probe for rapid determination of cytochrome P-450 CYP1A2 activity in humans.

AIM: To develop a rapid HPLC method for the determination of cytochrome P-450 CYP1A2 activity. METHODS: A 300-microL plasma was prepared by extraction with 5-mL chloroform/isopropanol (9:1), and beta-hydroxyletheophylline was added as internal standard (IS). Samples were separated on an ODS column by a gradient elution system, of which mobile phase consisted of 0.05% acetic acid, acetonitrile, and methanol. The compounds of interest were monitored at 282 nm by UV detector. RESULTS: No potential interfering peaks were found. Paraxanthine (17X), IS and caffeine (137X) were rapidly eluted with baseline resolution, and their retention time was less than 13 min. The detection limits of both 17X and 137X were 0.1 mumol.L-1. Linear relations ranged over 1-100 mumol.L-1 and 1-200 mumol.L-1 with correlation coefficient of 0.9999 and 0.9987, respectively, for 17X and 137X. The coefficients of variation were within 6% for 17X, and 10% for 137X. The average recoveries for both compounds were ranged from 96% to 108%. CONCLUSION: This method is sensitive and rapid, and can be used for population studies of CYP1A2.

Caffeine↗

PubMed1998

Clomipramine N-demethylation metabolism in human liver microsomes.

AIM: To study the effect of cytochrome P-450 (CYP450) inhibitors on clomipramine (Clo) N-demethylation in vitro. METHODS: The kinetic parameters of Clo N-demethylation in human liver microsomes were obtained by the Michaelis-Menten equation. The parameters after pretreatment with putative inhibitors of various CYP450 isoforms were compared with controls. RESULTS: K(m1), K(m2), Vmax1, Vmax2, Vmax1/K(m1), and Vmax2/K(m2) were (0.11 +/- 0.06), (24 +/- 14) mumol.L-1, (114 +/- 47), (428 +/- 188) nmol.g-1.min-1, (1.8 +/- 1.6), and (0.019 +/- 0.005) L.g-1.min-1, respectively. The interindividual variations for the last 4 parameters reached up to 2.5-, 7.3-, 3.4-, and 1.8-fold. At 5 mumol.L-1 of Clo, troleandomycin (Tro), furafylline (Fur), ditiocarb sodium (Dit), and S-mephenytoin (Mep) produced a marked inhibition on Clo N-demethylation while sulfaphenazole (Sul) and quinidine (Qui) had only slight effects. The inhibitory rates by Dit 30, Mep 500, Fur 10, Tro 10, Fur 80, Tro 200 and Fur 80 + Tro 200 mumol.L-1 were 27.0%, 32.9%, 42.8%, 40.5%, 63.9%, 66.4%, and 78.3%, respectively. The IC50 (95% confidence limits) for Fur and Tro were 27.7 (19.1-36.3) and 42.1 (20.9-63.3) mumol.L-1, respectively. CONCLUSIONS: The N-demethylation of Clo exhibited a biphasic behavior. This reaction was mediated mainly by both CYP1A2 and CYP3A4, to a minor extent by CYP2C19 at the low concentration of Clo in vitro.

Adult↗