Search PubMed⌕ Search

Biomedical subjects

T Yokoi

Publications and source records attributed to T Yokoi.

At least 73 records · Page 4Linked to original sources
PubMed2000

A significant role of human cytochrome P450 2C8 in amiodarone N-deethylation: an approach to predict the contribution with relative activity factor.

Human cytochrome P450 (CYP) isoforms involved in amiodarone N-deethylation were identified, and the relative contributions of these CYP isoforms were evaluated in different human liver microsomes. The mean K(M) and V(max) values of amiodarone N-deethylation in microsomes from six human livers were 31.6 +/- 7.5 microM and 1.2 +/- 0.7 pmol/min/pmol of CYP, respectively. Ketoconazole and anti-CYP3A antibodies strongly inhibited amiodarone N-deethylase activity in human liver microsomes at a substrate concentration of 50 microM. Of 15 recombinant human CYP enzymes (19 preparations), CYP1A1, CYP3A4, CYP1A2, CYP2D6, CYP2C8, and CYP2C19 catalyzed amiodarone N-deethylation. The amiodarone N-deethylase activity at a substrate concentration of 5 microM was significantly correlated with the paclitaxel 6alpha-hydroxylase activity (r = 0.84, P <.05) in the human liver microsomes, whereas the amiodarone N-deethylase activity at 100 microM was significantly correlated with the testosterone 6beta-hydroxylase activity (r = 0.94, P <.005). According to the concept of relative activity factor, it was clarified that CYP2C8 as well as CYP3A4 were significantly involved in amiodarone N-deethylation in human livers at clinically significant concentrations and that the contributions of CYP1A2, CYP2C19, and CYP2D6 were relatively minor. However, there was a large interindividual variability in the contribution of each CYP isoform to amiodarone N-deethylase activity in human liver; the relevance of these enzymes would be dependent on the content of the respective isoforms and on the amiodarone concentration in the liver.

Alkylation↗
PubMed2000

Formation of a dihydroxy metabolite of phenytoin in human liver microsomes/cytosol: roles of cytochromes P450 2C9, 2C19, and 3A4.

Formation of four oxidative metabolites from the anticonvulsant drug phenytoin (DPH) catalyzed by human liver microsomal cytochrome P450 (P450) enzymes was determined simultaneously. Under the conditions in which linearity for formation of 4'-hydroxylated DPH (4'-HPPH; main metabolite) was observed, human liver cytosol increased microsome-mediated DPH oxidation. 3',4'-Dihydroxylated product (3', 4'-diHPPH) formation was 10 to 40% of total DPH oxidation in the presence of liver cytosol. 3'-Hydroxy DPH formation was catalyzed by only one of the human liver microsomal samples examined and 3', 4'-dihydrodiol formation could not be detected in all samples. In the presence of liver cytosol, 3',4'-diHPPH formation activity from 100 microM 4'-HPPH was correlated with testosterone 6beta-hydroxylation activity and CYP3A4 content. However, 3', 4'-diHPPH formation using 1 or 10 microM 4'-HPPH as a substrate was not correlated with contents of any P450s or marker activities. Of 10 cDNA-expressed human P450 enzymes examined, CYP2C19, CYP2C9, and CYP3A4 catalyzed 3',4'-diHPPH formation from the primary hydroxylated metabolites (3'-hydroxy-DPH and 4'-HPPH). Fluvoxamine and anti-CYP2C antibody inhibited 3',4'-diHPPH formation from 10 microM 4'-HPPH in a human liver sample that contained relatively high levels of CYP2C, whereas ketoconazole and anti-CYP3A antibody showed inhibitory effects on the activities in liver microsomal samples in which CYP3A4 levels were relatively high. These results suggest that CYP2C9, CYP2C19, and CYP3A4 all have catalytic activities in 3',4'-diHPPH formation from primary hydroxylated metabolites in human liver and that the hepatic contents of these three P450 forms determine which P450 enzymes play major roles of DPH oxidation in individual humans.

Catalysis↗
PubMed2000

Roles of cytochromes P450 1A2, 2A6, and 2C8 in 5-fluorouracil formation from tegafur, an anticancer prodrug, in human liver microsomes.

Tegafur, an anticancer prodrug, is bioactivated to 5-fluorouracil (5-FU) mainly by cytochrome P450 (P450) enzymes. The conversion from tegafur into 5-FU catalyzed by human liver microsomal P450 enzymes was investigated. In fourteen cDNA-expressed human P450 enzymes having measurable activities, CYP1A2, CYP2A6, CYP2E1, and CYP3A5 were highly active in catalyzing 5-FU formation at a tegafur concentration of 100 microM. Kinetic analysis revealed that CYP1A2 had the highest V(max)/K(m) value and that the V(max) value of CYP2A6 was high in 5-FU formation. In human liver microsomes, the activities of 5-FU formation from 10 microM, 100 microM, and 1 mM tegafur were significantly correlated with both coumarin 7-hydroxylation (r = 0.83, 0.86, and 0.74) and paclitaxel 6 alpha-hydroxylation (r = 0.77, 0.62, and 0.85) activities, respectively. Coumarin efficiently inhibited the 5-FU formation activities from 100 microM and 1 mM tegafur catalyzed by human liver microsomes that had high coumarin 7-hydroxylation activity. On the other hand, furafylline, fluvoxamine, and quercetin, as well as coumarin, showed inhibitory effects in liver microsomes that had high catalytic activities of 5-FU formation. The other P450 inhibitors examined showed weak or no inhibition in human liver microsomes. Polyclonal anti-CYP1A2 antibody, monoclonal anti-CYP2A6, and anti-CYP2C8 antibodies inhibited 5-FU formation activities to different extents in those two microsomal samples. These results suggest that CYP1A2, CYP2A6, and CYP2C8 have important roles in human liver microsomal 5-FU formation and that the involvement of these three P450 forms differs among individual humans.

Antimetabolites, Antineoplastic↗
PubMed1999

The nucleotide sequence and genome organization of Sclerophthora macrospora virus B.

Sclerophthora macrospora Virus B (SmV B) found in S. macrospora, the pathogenic fungus responsible for downy mildew in gramineous plants, is a small icosahedral, monopartite virus containing a positive-strand ssRNA genome. In the present study, the complete nucleotide sequence of the SmV B genome was determined. The viral genome consists of 5533 nucleotides and has two large open reading frames (ORFs). ORF1 encodes a putative polyprotein containing the motifs of chymotrypsin-related serine protease and RNA-directed RNA polymerase. ORF2 encodes a capsid protein. The deduced amino acid sequence shows some similarity to those of certain positive-strand RNA viruses, but the genome organization is characteristic and distinct from those of other known fungal RNA viruses. These results suggest that SmV B should be classified into a new group of mycoviruses.

Amino Acid Sequence↗
PubMed1999

Sensitive assay of trimethylamine N-oxide in liver microsomes by headspace gas chromatography with flame thermionic detection.

To compare the trimethylamine N-oxygenase activity of liver microsomes from house musk shrew (Suncus murinus) and rat, a sensitive method for the quantitation of trimethylamine (TMA) N-oxide was developed using gas chromatography with flame thermionic detection. The limit of quantification was 0.5 microM and the calibration curve was linear at least up to 5 microM in incubations containing liver microsomal preparations from Suncus. The intra-day RSD values ranged from 10.4 to 12.8 at 0.5 microM and from 3.5 to 6.7 at 5 microM. The inter-day RSD values were 11.6 and 6.5 at 0.5 and 5 microM, respectively. This method provides a sensitive assay for TMA N-oxygenase activity in liver microsomes. Using this method we found that Suncus was capable of N-oxidizing trimethylamine at a very slow rate.

Animals↗
PubMed1999

Intraductal spread of invasive breast carcinoma has a positive correlation with c-erb B-2 overexpression and vascular invasion.

BACKGROUND: Studies of the histologic characteristics and biologic behavior of the intraductal spread of breast carcinoma are critically important in that they may lead to the identification of a unique spread pattern rather than a noninvasive lesion. METHODS: Paraffin embedded specimens of 187 primary invasive breast carcinomas and 4 noninvasive ductal carcinomas, obtained by wide excision, quadrantectomy, total glandectomy, or mastectomy, were studied immunohistochemically. The overexpression of c-erb B-2, p53, bcl-2, and MIB-1, as well as the histologic characteristics of intraductal spread (such as histologic features and histologic grade), were assessed. Chi-square and Fisher exact tests were conducted to evaluate significant differences; the Macintosh for Expert StatView 4.0 system was used to conduct these tests. RESULTS: The histologic characteristics of intraductal spread were similar to those of noninvasive ductal carcinoma. However, the expressions of c-erb B-2, p53, and other biologic markers of intraductal spread were similar to those of the main invasive tumor. The overexpression of c-erb B-2 protein was found more often in the group that was positive for intraductal spread than in the group that was negative (P < 0.01). Intraductal spread was found more often in the group that was positive for lymphatic and venous invasion than in the group that was negative (P < 0.005). Subnipple margin positive status was related closely to intraductal spread (P < 0.0001). CONCLUSIONS: The positive correlation between intraductal spread and c-erb B-2 overexpression as well as lymphatic, venous invasion was recognized, and it was determined that intraductal spread of invasive breast carcinoma possesses an invasive and metastatic potential that is distinct from noninvasive ductal carcinoma.

Antigens, Nuclear↗
PubMed1999

Tyrosine phosphorylation of STAT3 by leptin through leptin receptor in mouse metaphase 2 stage oocyte.

Leptin is the product of the obese gene (ob), and is secreted in plasma from mature adipocytes. It has been recently reported that leptin is synthesized in granulosa and cumulus cells within the follicle of the ovary, and is present in mature human oocytes, suggesting possible roles of leptin in several aspects of pre- and post-ovulatory follicular development. On the other hand, STAT (Signal Transducer and Activator of Transcription) transcription factors are involved in leptin-associated signal transduction. In this report, we studied the expression of leptin receptor and STAT3 activation by leptin in metaphase 2 stage (M2) oocytes. Reverse transcriptase-polymerase chain reaction (RT-PCR) and immunoblotting showed that mRNA and protein of leptin receptor were expressed in M2 stage oocyte. Leptin at 15 ng/ml, the concentration observed in follicular fluid, caused tyrosine phosphorylation of STAT3 in mouse M2 stage oocytes. These results suggest possible roles of leptin in several aspects during oocyte maturation by activating the STAT signal transduction pathway.

Adipocytes↗
PubMed1999

Primary low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma with polypoid appearance. Polypoid gastric MALT lymphoma: A clinicopathologic study of eight cases.

In the current study, we report eight cases with primary low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma endoscopically characterized by polypoid lesions in order to highlight their clinicopathologic significance. Four patients were male, their ages ranging from 40 to 78 years old. The resected specimens revealed a histology of low-grade MALT lymphoma characterized by dense lymphocytic infiltration predominantly in the submucosa and a relatively monotonous proliferation of centrocyte-like cells with reactive follicles and infrequent lymphoepithelial lesions. The tumor cells were of CD5-, CD10-, CD20+, BCL2+ and cycline D1- phenotype, and showed a monoclonal rearrangement of immunoglobulin heavy chain genes in the five of six cases examined. Interestingly, Helicobacter pylori (H. pylori) was detected in three (37.5%) of the eight patients, which was significantly lower than previous reports. Two of the H. pylori-positive cases initially underwent H. pylori eradication, but showed no change in their lymphomas after the cure of H. pylori infection. The clinicopathologic findings of the present cases appeared to closely resemble those of colorectal MALT lymphoma with a polypoid appearance and few association of H. pylori infection in their pathogenesis. These gastric polypoid cases may merit separate consideration because of the therapeutic problems they pose.

Adult↗
PubMed1999

Genetic variants of calcitonin receptor and breast cancer in Japanese.

Calcitonin (CT) inhibits the growth of human breast cancer cell lines and calcitonin receptor (CTR) is expressed in breast cancer lines and breast cancer tissue. In this study, the allele frequencies of the CTR gene were compared in the peripheral blood and tumour from 46 breast cancer patients with 50 peripheral blood samples from Japanese women. The allele frequencies of CTR gene did not differ between them. There was no significant association of CTR allele frequencies in invasive breast carcinomas. These results indicate that allelic variation of the CTR gene is not a significant risk factor for the development of breast carcinoma in Japanese women. Further studies are needed to clarify the role of CT and CTR in human breast tissue.

Journal Article↗
PubMed1999

Isoform selective inhibition and inactivation of human cytochrome P450s by methylenedioxyphenyl compounds.

1. A series of methylenedioxyphenyl compounds were evaluated for their inhibitory and inactivation effects on nine human cytochrome P450 (CYP) activities using microsomes from human B-lymphoblast cells expressing specific human CYP isoforms. 2. Methylenedioxyphenyl compounds which possess a bulky structure such as 1,4-benzothiazine showed substantial inhibition of S-warfarin 7-hydroxylation catalysed by CYP2C9, S-mephenytoin 4'-hydroxylation by CYP2C19, bufuralol 1'-hydroxylation by CYP2D6, and testosterone 6beta-hydroxylation by CYP3A4. Regarding ethoxyresorufin O-deethylation catalysed by CYP1A1 and benzyloxyresorufin O-dealkylation by CYP2B6, the subtle change of a substitution of the 1,4-benzothiazine structure affected the inhibition selectivity. Ethoxyresorufin O-deethylation by CYP1A2, coumarin 7-hydroxylation by CYP2A6, and chlorzoxazone 6-hydroxylation by CYP2E1 were not inhibited by almost any of the methylenedioxyphenyl compounds. The inhibitory effects of methylenedioxyphenyl compounds that possess a short chain amino group on the human CYP isoforms were not significant. 3. The methylenedioxyphenyl compounds inactivated CYP1A1 (k(inact) = 0.034 min(-1) and K(i) = 0.81 microM), CYP2C9 (k(inact) = 0.041 and 0.042 min(-1) and K(i) = 0.56 and 0.15 microM), CYP2D6 (k(inact) = 0.044-0.339 min(-1) and K(i) = 0.21-19.88 microM), and CYP3A4 (k(inact) = 0.076-0.251 min(-1) and K(i) = 0.25-0.69 microM). These results suggested that the methylenedioxyphenyl compounds investigated in this study would be potent mechanism-based inactivators of these human CYP isoforms. In contrast, CYP2B6 and CYP2C19 were not inactivated. 4. The present study suggested that the selectivity of inhibition or inactivation of human CYP isoforms by methylenedioxyphenyl compounds may vary according to the structure of the side chain.

Aryl Hydrocarbon Hydroxylases↗
PubMed1999

Activation of phenacetin O-deethylase activity by alpha-naphthoflavone in human liver microsomes.

1. The roles of different human cytochrome P450s (CYP) in phenacetin O-deethylation were investigated using human liver microsomes and recombinant proteins. Phenacetin O-deethylase (POD) activities in human liver microsomes at substrate concentrations of 10 and 500 microM were inhibited by 0.1 and 1 microM alpha-naphthoflavone and activated by 10 and 100 microM alpha-naphthoflavone. The activation of POD activity in human liver microsomes by alphanaphthoflavone was inhibited by 100 microM aniline, anti-CYP2E1 antibody, 1 microM ketoconazole and anti-CYP3A4 antibody. 2. In recombinant CYP from human B-lymphoblast cells, POD activities at a phenacetin concentration of 500 microM were detected for CYP2E1 and CYP3A4, as well as CYP1A2, CYP1A1, CYP2C19, CYP2C9 and CYP2A6. In recombinant CYP from human B-lymphoblast cells or baculovirus-infected insect cells and in reconstituted systems, a requirement of cytochrome b5 (b5) for POD activities catalysed by CYP2E1 and CYP3A4 was observed. The activation of POD activity by alpha-naphthoflavone was observed for CYP3A4, but not for CYP2E1. Co-expression of b5 with CYP3A4 enhanced the activation of POD activity by alpha-naphthoflavone. 3. In the absence of alpha-naphthoflavone, the POD activity in pooled human liver microsomes at 500 microM phenacetin was significantly inhibited (p<0.0001) by 10 microM fluvoxamine, but not by 1 microM ketoconazole. In the presence of alpha-naphthoflavone, the activity was significantly inhibited (p<0.0001) by 1 microM ketoconazole, but not by 10 microM fluvoxamine. 4. Inter-individual differences in the effects of alpha-naphthoflavone on POD activity in human liver microsomes were observed, and the involvement of CYP3A4 as well as CYP1A2 in POD activity in human liver was identified even at a low substrate concentration.

Aniline Compounds↗
PubMed1999

Stereoselective S-oxidation and reduction of flosequinan in rat.

1. The stereoselective S-oxidation and reduction pathways of flosequinan [(+/-)-7-fluoro-1-methyl-3-methylsulphinyl-4-quinolone] in rat were investigated in vitro. 2. Cytosol from both the liver and kidney catalysed the reduction of R(+)-flosequinan (R-FSO) and S(-)-flosequinan (S-FSO) to flosequinan sulphide (FS, 7-fluoro-1-methyl-3-methylthio-4-quinolone). Flosequinan sulphone (FSO2, 7-fluoro-1-methyl-3-methylsulphonyl-4-quinolone) was not reduced to R-FSO or S-FSO. 3. Liver microsomes catalysed four different S-oxidation pathways in the presence of NADPH, namely oxidation of FS to R-FSO and S-FSO and from R-FSO and S-FSO to FSO2. The formation of R-FSO and S-FSO from FS each exhibited a biphasic kinetic pattern, indicating that at least two distinct enzymes were involved. The pathway from FS to R-FSO appeared mainly catalysed by flavin-containing monooxygenases (FMO). 4. S-oxidation of FS to R-FSO was more rapid than that of FS to S-FSO. S-oxidation of FS to either R-FSO or S-FSO in liver microsomes was more rapid than that of either R-FSO or S-FSO to FSO2. 5. Microsomes from both the kidney and lung catalysed the stereoselective S-oxidation of FS to R-FSO, and FMO was likely to have participated in these reactions.

Animals↗
PubMed1999

Implementation and quantitative evaluation of analytical methods for attenuation correction in SPECT: a phantom study.

Three differing exact methods of inverting the two-dimensional (2D) exponential Radon transform were implemented and evaluated quantitatively with a phantom study. The phantom had the shape of a pie-chart divided into six cavities, each 480 ml in volume and 10 cm in height, that were symmetrically positioned in a cylinder that was 20 cm in diameter and 10 cm in height. This phantom tests for linearity between true activity concentration and measured activity concentration, and it is denoted as a linearity phantom in the present study. Each cavity contained a different concentration of a homogeneous solution of 99mTc (74, 148, 222, 296, 370 and 444 kBq ml(-1)). Data acquisition was performed with two energy windows: a 20% photopeak energy window set symmetrically over the 140 keV of 99mTc and a secondary 5% energy window set over the 122 keV peak. We optimized a triple-energy window scatter correction method for a gamma camera-collimator system to obtain accurate scatter-corrected projections. A circular ROI 3 cm in diameter was identified over each cavity region, and count density (counts per pixel) was calculated. This value was converted to activity concentration (kBq ml(-1)) using a cross-calibration coefficient between SPECT counts and the gamma well counter. The relation between true activity (x) and measured activity concentration (y) was fitted to a line using the least-squares method. Regression lines were y = 0.63 + 1.0255x (R2 = 0.9987), y = -2.62 + 1.0278x (R2 = 0.9995), and y = 0.092 + 1.0241x (R2 = 0.9989) for the Bellini, Inouye and Metz-Pan methods respectively. In another phantom study using two different types of phantoms, contrast of a cold region in the two was 96% and 101% for all three methods. Combined optimized scatter correction and analytical attenuation correction methods achieve good accuracy in quantification of activity distribution with a uniform attenuating medium.

Humans↗
PubMed1999

Inhibition of benzo[a]pyrene-induced mutagenesis by (-)-epigallocatechin gallate in the lung of rpsL transgenic mice.

Epigallocatechin gallate (EGCG) is a major water-soluble component of green tea. The antimutagenic activity of EGCG against benzo[a]pyrene (B[a]P)-induced mutations was assessed by using transgenic mice carrying the rpsL gene as a monitor of mutations. Seven-week-old male mice were given drinking water containing EGCG for 3 weeks. On day 7, mice were treated with a single i.p. injection of B[a]P (500 mg/kg body wt). Two weeks after the injection, the mutations in the rpsL gene were analyzed. B[a]P treatment resulted in an approximately 4-fold increase of mutation frequency at the rpsL gene in the lung. An approximately 60% reduction in the B[a]P-induced mutations in the lung was observed when mice were given EGCG at concentrations >0.005%. B[a]P-induced mutations mainly occurred at G:C basepairs in the several specific nucleotide sequences of the rpsL gene. These were AGG, CGG, CGT, TGG, TGC and GGT: all of them contained a guanine residue. Mutations seen similarly in the human Ki-ras codon 12 or p53 codons 157, 248, and 273 of lung tumor were also found in the rpsL gene, and the mutations were suppressed by the EGCG treatment. In conclusion, the antimutagenic effects of EGCG for B[a]P-induced mutagenesis in vivo suggest that drinking green tea may reduce the tumor-initiating potency of B[a]P in the lung.

Animals↗
PubMed1999

Genetic polymorphism in the 5'-flanking region of human CYP1A2 gene: effect on the CYP1A2 inducibility in humans.

A genetic polymorphism was identified in the 5'-flanking region of human CYP1A2 gene, and its effect on the transcriptional activation of the CYP1A2 gene was investigated. Nucleotide sequence analysis revealed the existence of a point mutation from guanine (wild type) to adenine (mutated type) at position -2964 in the gene. This point mutation was detected by a polymerase chain reaction-restriction fragment length polymorphism method using DdeI or BslI restriction enzyme, and was proven to be genetically inherited. Allele frequency in 116 Japanese subjects showed 0.77 and 0.23 for the wild and mutated types of allele, respectively. The point mutation caused a significant decrease of CYP1A2 activity measured by the rate of caffeine 3-demethylation in Japanese smokers (p<0.05). Gel retardation analysis showed the existence of protein bound to the polymorphic locus. These results suggest that this polymorphism is a causal factor of decreased CYP1A2 inducibility.

Alleles↗
PubMed1999

Homologous unequal cross-over within the human CYP2A gene cluster as a mechanism for the deletion of the entire CYP2A6 gene associated with the poor metabolizer phenotype.

To clarify the molecular mechanisms involved in the generation of the CYP2A6 gene deletion (E-type variant), we analyzed the CYP2A7 gene, which is located in the 5'-flanking region of the CYP2A6 gene, from individuals with the E-type variant and compared it with the sequences of wild type CYP2A7 and CYP2A6 genes. The 3'-downstream sequence (up to 324 bp from the SacI site in exon 9) of the CYP2A7 gene of the E-type variant is identical to that of the wild CYP2A7 gene. However, the 3'-downstream sequence (starting from 325 bp from the SacI site in exon 9) of the CYP2A7 gene of the E-type variant is identical to that of the wild CYP2A6 gene, indicating that the 3'-downstream region of CYP2A7 and the 3'-downstream region of CYP2A6 linked directly eliminating the whole CYP2A6 gene. PCR analysis using primers specific to the CYP2A7 gene and the CYP2A6 and CYP2A7 genes confirmed that all DNA samples obtained from 7 individuals carrying the E-type variant possessed the same break points. These results indicate that the breakpoint of the CYP2A6 gene deletion lies in the 3'-downstream region of the CYP2A7 and CYP2A6 genes.

Alleles↗
PubMed1999

Effects of chronic administration of glucocorticoid on midazolam pharmacokinetics in humans.

Midazolam (MDZ) is metabolized by CYP3A. Glucocorticoids are potent inducers of CYP3A in humans. The possible interaction between intravenous MDZ and chronically administered glucocorticoids was investigated during surgery in patients. MDZ (0.2 mg/kg) was administered intravenously to 8 patients taking glucocorticoid chronically and 10 patients not taking glucocorticoid. In patients taking glucocorticoid, the AUC0-infinity and CL of MDZ was decreased to 63.9% (16.3 +/- 10.5 vs 25.5 +/- 20.7 microg x min/mL) and increased to 127.5% (16.7 +/- 10.7 vs 13.1 +/- 8.3 mL/min/kg) of that in the control group, respectively. The terminal t1/2 values of MDZ were similar in two groups. In patients taking glucocorticoid, the AUC0-infinity of 1'-hydroxymidazolam (1'-OH MDZ) was 66.7% of that in the control group (7.6 +/- 2.6 vs 11.4 +/- 9.7 microg x min/mL), and the terminal t1/2 of 1'-OH MDZ was significantly (p < 0.01) decreased (1.8 +/- 0.5 vs 3.0 +/- 0.8 hr). Accumulative urinary excretion of 1'-OH MDZ glucuronide was increased to 157.6%. These observations might be results from induction of CYP3A4 and/or UDP-glucuronosyltransferase by glucocorticoids.

Adult↗