Search PubMed⌕ Search

Biomedical subjects

M Nakajima

Publications and source records attributed to M Nakajima.

At least 289 records · Page 16Linked to original sources
PubMed1999

[A case of nephrotic syndrome associated with myasthenia gravis and malignant thymoma].

A 26-year-old woman who presented facial and lower leg edema associated with massive proteinuria was admitted to our hospital in February 1992. Nine months before this admission, she exhibited myasthenia gravis and malignant thymoma, and underwent total thymectomy. On admission, there was no symptom of myasthenia gravis. She was diagnosed as having nephrotic syndrome and the first renal biopsy was performed. The histological findings showed membranous nephropathy. Immunofluorescent microscopy revealed that IgG and C3 were stained in a granular pattern in the periphery, and subepithelial deposits were observed in the basement membrane of the glomerulus by electron microscopy. With the administration of prednisolone, proteinuria disappeared and the nephrotic syndrome remitted. She was admitted again in January 1993 due to proteinuria and lower leg edema following cystitis. The findings of the second renal biopsy were unremarkable. She was administered cyclosporin A to improve the nephrotic syndrome and to reduce the side effects of prednisolone. The proteinuria disappeared again and this effect was dependent on the dose of cyclosporin A. Since the first administration, no symptoms of myasthenia gravis or malignant thymoma have been observed. The relationships among myasthenia gravis, malignant thymoma and nephrotic syndrome were examined. Although the first renal biopsy findings showed membranous nephropathy, from the therapeutic responses of both prednisolone and cyclosporin A, the main course of proteinuria in this case may have been due to minimal change nephrotic syndrome. We consider this case of nephrotic syndrome to be important considering its etiology and the relationship between the histological findings and its clinical course.

Adult↗
PubMed1999

[Intracerebral hemorrhage associated with long-lasting deficiency of factor XIII].

A 5-year-old boy had an intracerebral hematoma evacuated from the left parieto-occipital region at a local hospital. There was a difficulty in hemostasis during the operation. Postoperatively his neurological state gradually deteriorated. CT scans showed a gradual increase in intracerebral hemorrhage at the operated site. He was transferred to our clinic for further treatment. The preoperative blood coagulation profile showed that the activity of factor XIII was only 4%. The hematoma was removed without any trouble under administration of factor XIII. Postoperative course was also uneventful although the plasma level of factor XIII did not go up higher than 26% in spite of its daily administration. Although factor XIII administration was terminated one month after cranioplasty, the patient showed good recovery and the level of factor XIII spontaneously normalized in 6 months. The cause of the extremely low level of factor XIII in this case is not known, but it could be ascribed to massive hemorrhage.

Cerebral Hemorrhage↗
PubMed1999

Inhibitory effects of azelastine and its metabolites on drug oxidation catalyzed by human cytochrome P-450 enzymes.

Azelastine, an antiallergy and antiasthmatic drug, has been reported to be metabolized mainly to desmethylazelastine and 6-hydroxyazelastine in mammals. In the present study, the inhibitory effects of azelastine and its two metabolites on human cytochrome P-450 (CYP) isoform-dependent reactions were investigated to predict the drug interactions of azelastine using microsomes from human B-lymphoblast cells expressing CYP. The specific activities for human CYP isoforms included: 7-ethoxyresorufin O-deethylation (CYP1A1), phenacetin O-deethylation (CYP1A2), coumarin 7-hydroxylation (CYP2A6), 7-benzyloxyresorufin O-dealkylation (CYP2B6), S-warfarin 7-hydroxylation (CYP2C9), S-mephenytoin 4'-hydroxylation (CYP2C19), bufuralol 1'-hydroxylation (CYP2D6), chlorzoxazone 6-hydroxylation (CYP2E1), and testosterone 6beta-hydroxylation (CYP3A4). In almost all the activities, desmethylazelastine exhibited stronger inhibition than azelastine and 6-hydroxyazelastine. Desmethylazelastine, but not azelastine and 6-hydroxyazelastine, uncompetitively inhibited CYP2B6 activity (Ki = 32.6 +/- 4.8 microM). Azelastine, desmethylazelastine, and 6-hydroxyazelastine competitively inhibited CYP2C9 activity (Ki = 13. 9 +/- 1.8, 15.0 +/- 3.1, and 17.0 +/- 4.1 microM, respectively), CYP2C19 activity (Ki = 21.9 +/- 2.2, 7.3 +/- 1.6, and 9.3 +/- 1.6 microM, respectively), and CYP2D6 activity (Ki = 1.2 +/- 0.1, 1.5 +/- 0.2, and 3.0 +/- 0.5 microM, respectively). Azelastine and desmethylazelastine competitively inhibited CYP3A4 activity (Ki = 23. 7 +/- 4.6 and 13.2 +/- 2.3 microM). 6-Hydroxyazelastine interfered with the determination of testosterone 6beta-hydroxylation by HPLC. CYP1A2, CYP2A6, and CYP2E1 activities were not significantly inhibited by azelastine and the two metabolites. Among the human CYPs tested, the inhibitory effects of azelastine and its two metabolites were the most potent on human CYP2D6. In consideration of the Ki values and the concentration of azelastine and desmethylazelastine in human livers after chronic oral administration of azelastine, the possibility of in vivo drug interaction of azelastine and other drugs that are mainly metabolized by CYP2D6 was suggested although it might not cause critical side effects. The inhibition of CYP2C9, CYP2C19, and CYP3A4 activity by azelastine and its two metabolites might be clinically insignificant.

Anti-Allergic Agents↗
PubMed1999

[Benign clear cell tumor of the lung diagnosed by transbronchial biopsy].

A 26-year-old woman had an abnormal shadow on chest X-ray films during a general medical examination. A chest roentgenogram showed a nodular shadow 8 mm in diameter in the middle field of the right lung. Transbronchial biopsy specimens revealed that the coin lesion was a benign clear cell tumor. Benign clear cell tumors of the lung are rare; only 21 cases, including the present case, have been reported in Japan. Although the diagnosis in most of the cases reported required an open thoracotomy, for our patient the diagnosis was based solely on the findings of a transbronchial biopsy.

Adult↗
PubMed1999

Involvement of CYP2E1 as A low-affinity enzyme in phenacetin O-deethylation in human liver microsomes.

Phenacetin O-deethylation (POD) exhibits biphasic kinetics in human liver microsomes. Although cytochrome P-450 (CYP) 1A2 is responsible for the high-affinity component of POD, the enzyme(s) that catalyzes the low-affinity reaction is still unknown. We examined the roles of human CYPs in POD by using human liver microsomes and recombinant CYPs from baculovirus-infected insect cells. Of the recombinant CYPs studied, CYP1A2 showed the highest POD activity. CYP1A1, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 also showed POD activity at 500 microM phenacetin. K(M) values of recombinant CYP1A2 and CYP2E1 (28 +/- 2 microM and 785 +/- 125 microM, respectively) were similar to those of the high- and low-affinity components of POD in pooled human liver microsomes (15 +/- 5 and 894 +/- 189 microM, respectively). Fluvoxamine (10 microM) and anti-CYP1A2 antibodies potently inhibited POD activity at 500 microM phenacetin in pooled human liver microsomes to 22.8 and 34.2% of controls, respectively. CYP2E1 inhibitors diethyldithiocarbamate and aniline also reduced POD activity. The combination of fluvoxamine (10 microM) and aniline (1 mM) further inhibited the residual POD activity not inhibited by fluvoxamine alone. Microsomal POD activity in 12 human livers in the absence of fluvoxamine was correlated with immunoquantified CYP1A2 levels (r = 0.961, p <.001) and, in the presence of 10 microM fluvoxamine, was correlated with immunoquantified CYP2E1 levels (r = 0.589, p <.01) or chlorzoxazone 6-hydroxylase activity (r = 0.823, p <.001). These results suggest that CYP2E1 is responsible for the low-affinity component of POD in human liver microsomes.

Analgesics, Non-Narcotic↗
PubMed1999

[Electrophysiology of juvenile muscular atrophy of unilateral upper limb (Hirayama's disease)].

To examine the validity of electrodiagnostic tests to help diagnosis and to evaluate disease activity of juvenile atrophy of unilateral upper limb (Hirayama's disease), we reviewed the results of nerve conduction studies, motor unit number estimates, electromyography, and somatosensory evoked potentials in consecutive 38 patients. There was selective involvement of the C8-T1 myotomes, in which motor unit loss was more prominent in the abductor digiti minimi than in the abductor pollicis brevis muscles, and F wave persistency was decreased out of proportion to the motor unit loss. These findings may help diagnosis. With respect to the disease activity and treatment, denervation potentials in the flexor carpi radialis muscle were more frequent in patients with shorter disease duration than those with longer duration. Median F wave persistency was greater in patients treated with neck brace than in patients without the treatment. These parameters can monitor the disease activity and efficacy of treatment.

Adolescent↗
PubMed1999

[Angiographic findings and histological localization of indocyanine green in N-methyl-N-nitrosourea induced retinal degeneration in rats].

PURPOSE: We used N-methyl-N-nitrosourea (MNU) to induce chorioretinopathy as a model of retinitis pigmentosa, and compared the histological localization of indocyanine green (ICG) with ICG angiographic features. METHODS: Brown-Norway pigmented rats received a single intraperitoneal injection of MNU (75 mg/kg body weight). At 3 and 21 days after treatment, we compared ICG angiographic findings with histological localization of ICG in the retina and choroid. Histological localization of ICG was observed with an infrared light microscope. RESULTS: 3 days after treatment, destruction of the photoreceptor cells and photoreceptor segments had developed, and the retinal pigment epithelial cells (RPEs) were also damaged. In ICG angiography, diffuse hyperfluorescence was evident. In histological localization of ICG, RPEs were stained by ICG, and ICG was seen in the sensory retina through the damaged RPEs. At 21 days after treatment, the inner nuclear layer directly contact with the choroid. The photoreceptor cells, RPEs and choriocapillaris had disappeared. In ICG angiography, hypofluorescence was seen in the chorioretinal atrophic area. In histological localization of ICG, there was no ICG in the atrophic area, but ICG leaked from the remaining choriocapillaris into the neighboring sensory retina. CONCLUSION: These results support the precise interpretation of ICG angiographic findings in clinical use.

Animals↗
PubMed1999

Enhancement of cytochrome P-450 3A4 catalytic activities by cytochrome b(5) in bacterial membranes.

Activities of testosterone, nifedipine, and midazolam oxidation by recombinant cytochrome P-450 (P-450) 3A4 coexpressed with human NADPH-P-450 reductase (NPR) in bacterial membranes (CYP3A4/NPR membranes) were determined in comparison with those of other recombinant systems and of human liver microsomes with high contents of CYP3A4. Growth conditions for Escherichia coli transformed with the bicistronic construct affected expression levels of CYP3A4 and NPR; an excess of NPR over P-450 in membrane preparations enhanced CYP3A4-dependent testosterone 6beta-hydroxylation activities of the CYP3A4/NPR membranes. Cytochrome b(5) (b(5)) and apolipoprotein b(5) further enhanced the testosterone 6beta-hydroxylation activities of CYP3A4/NPR membranes after addition to either bacterial membranes or purified enzymes. NPR was observed to enhance catalytic activity when added to the CYP3A4/NPR membranes, either in the form of bacterial membranes or as purified NPR (in combination with cholate and b(5)). Apparent maximal activities of testosterone 6beta-hydroxylation in CYP3A4/NPR membranes were obtained when the molar ratio of CYP3A4/NPR/b(5) was adjusted to 1:2:1 by mixing membranes containing each protein. Testosterone 6beta-hydroxylation, nifedipine oxidation, and midazolam 4- and 1'-hydroxylation activities in CYP3A4/NPR membranes plus b(5) systems were similar to those measured with microsomes of insect cells coexpressing CYP3A4 with NPR and/or of human liver microsomes, based on equivalent CYP3A4 contents. These results suggest that CYP3A4/NPR membrane systems containing b(5) are very useful models for prediction of the rates for liver microsomal CYP3A4-dependent drug oxidations.

Anesthetics, Intravenous↗
PubMed1999

Atypical Rathke's cleft cyst associated with ossification.

We report a case of symptomatic Rathke's cleft cyst with ossification. CT scans showed curvilinear calcification on the wall of the cyst. MR images revealed a cystic sellar lesion with a nodular solid mass extending to the floor of the third ventricle. This case shows that calcification of the suprasellar cyst does not always suggest craniopharyngioma. Rathke's cysts should be histologically differentiated from craniopharyngiomas because their treatments are different.

Adult↗
PubMed1999

[Eosinophilia and cough induced by resumption of cigarette smoking in a beginning smoker recovering from acute respiratory failure].

A 23-year-old man was admitted to the hospital because of acute respiratory failure accompanied by high fever and severe cough. He had started smoking about 3 weeks earlier and had gradually increased the number of cigarettes he smoked each day. After the number of cigarettes reached 10 per day, the patient experienced cough with serous sputum, high fever (38 degrees C) and dyspnea. Chest X-ray films revealed diffuse, peripheral shadows predominantly in the right lung. The patient was treated with an intravenous drip infusion of antibiotics (FMOX). On the second day of hospitalization, the dyspnea and chest X-ray shadows rapidly resolved. Although the cause of respiratory failure and diffuse shadows on chest X-ray films remained unclear, the patient was discharged. However, on the day of discharge, he smoked cigarettes and experienced cough with serous sputum for a few hours the following morning. He was readmitted for evaluation. We previously reported a case of smoking-induced acute eosinophilic pneumonia (AEP). We suspected that the present case was AEP induced by cigarette smoking but did not perform bronchoalveolar lavage or transbronchial lung biopsy for a definitive diagnosis. Although we did perform a provocation test, the patient demonstrated no respiratory symptoms without cough and respiratory failure. Blood gas analysis and pulmonary function tests also revealed no abnormalities. However, the eosinophil count (3066/mu/l) and percentage (42%) in peripheral blood increased after the patient resumed cigarette smoking, and returned to normal ranges after smoking cessation. These results pointed to a correlation between cigarette smoking and eosinophilia. This case suggested that in some patients, AEP may be induced by cigarette smoking, but does not recur after the resumption of smoking.

Acute Disease↗
PubMed1999

[Chronic bronchitis].

Chronic bronchitis (CB) is diagnosed from symptoms. It is important for the diagnosis to distinguish from other diseases accompanying similar symptoms. Recently, some diseases such as diffuse panbronchiolitis (DPB) have been recognized to have some characteristics different from CB, which used to include these diseases. The pathogenesis of CB is mostly smoking and to quit smoking is the basic and most important therapy. Target of medication in CB consists of hypersecretion, airway limitation and infection. A 14-membered ring macrolide such as erythromycin has been found to be effective in some patients with CB.

Anti-Bacterial Agents↗
PubMed1999

Oxidation of troglitazone to a quinone-type metabolite catalyzed by cytochrome P-450 2C8 and P-450 3A4 in human liver microsomes.

Troglitazone, a new oral antidiabetic drug, is reported to be mostly metabolized to its conjugates and not to be oxidized by cytochrome P-450 (P-450) enzymes. Of fourteen cDNA-expressed human P-450 enzymes examined, CYP1A1, CYP2C8, CYP2C19, and CYP3A4 were active in catalyzing formation of a quinone-type metabolite at a concentration of 10 microM troglitazone, whereas CYP3A4 had the highest catalytic activity at 100 microM substrate. In human liver microsomes, rates of the quinone-type metabolite formation (at 100 microM) were correlated well with rates of testosterone 6beta-hydroxylation (r = 0.98), but those at 10 microM troglitazone were not correlated with any of several marker activities of P-450 enzymes. Quercetin efficiently inhibited quinone-type metabolite formation (at 10 microM troglitazone) in human samples that contained relatively high levels of CYP2C, whereas ketoconazole affected these activities in liver microsomes in which CYP3A4 levels were relatively high. Anti-CYP2C antibodies strongly inhibited quinone-type metabolite formation (at 10 microM troglitazone) in CYP2C-rich human liver microsomes (by approximately 85%); the intensity of this effect depended on the human samples and their P-450 status. The results suggest that in human liver both CYP2C8 and CYP3A4 have major roles in quinone-type metabolite formation and that the hepatic contents of these two P-450 forms determine which P-450 enzymes play major roles in individual humans. CYP3A4 may be expected to play a role in formation of quinone-type metabolite from troglitazone even at a low concentration in humans.

Aryl Hydrocarbon Hydroxylases↗
PubMed1999

[Infratentorial hemorrhage following supratentorial surgery].

Hemorrhage in regions remote from the site of initial intracranial operations is rare, but does occur. We report three cases of cerebellar hemorrhage that developed after supratentorial surgery, all of which had similar clinical findings and CT images. The first case was a 37-year-old man with a craniopharyngioma in the suprasellar lesion. Partial removal of the tumor was performed through frontal craniotomy and the translaminaterminals approach. A large quantity of cerebospinal fluid (CSF) was suctioned from the third ventricle during the operation, resulting in marked brain shrinkage. The second and third cases were 34- and 51-year-old women with unruptured right middle cerebral aneurysms. Clipping of the aneurysms through the pterional approach was performed in both cases. In the second case, CSF was suctioned in large quantity from the carotid and prechiasmal cistern at the operation, resulting in marked brain shrinkage. In the third case, however, only a small volume of CSF was suctioned from the carotid and prechiasmal cistern during the operation, and no marked brain shrinkage was observed. CT scan showed that the hematomas were located mainly in the subdural or the subarachnoid spaces over the cerebellar hemisphere and partially extending into the cerebellar cortex. The mechanism of cerebellar hemorrhage in these series of patients was thought to be multifactorial. The possible etiology for cerebellar hemorrhage in the three cases presented was examined, including the role of CSF suction during surgery and disturbance of venous circulation in the posterior fossa. Suction of the CSF may cause intracranial hypotension. Further reduction of intracranial pressure leads to an increased transluminal venous pressure. There was no episode of hypertension or disturbed blood coagulation during or after the operation. The preoperative angiogram also revealed no abnormality at the region of the posterior fossa. Neuroimaging of infratentorial hemorrhage after supratentorial craniotomy is obviously different from that of hypertensive cerebellar hemorrhage. From the shape or extension of the hemorrhage, the main vessels of hemorrhage are the superior vermian vein and their tributaries damaged by stretching and tearing of these vessels. These vessels are not demonstrable in the angiogram, therefore there is no evidence for this hypothesis and the etiology is still unclear. There is no doubt, however, that there was a disturbance of venous circulation in this complication. We would like to emphasize the possibility of this complication. Patients who show signs of difficulty in awaking from anesthesia or the development of new neurological deficits not attributed to direct operative procedure after supratentorial craniotomy must be evaluated early, with adequate imaging including the posterior fossa.

Adult↗
PubMed1999

Relative expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 in mouse renal cell carcinoma cells regulates their metastatic potential.

To clarify the significance of the balance between matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) in the progression of renal cell carcinoma, we transfected both the MMP-2 and TIMP-2 genes simultaneously into RenCa, a mouse renal cell carcinoma cell line that does not express detectable levels of either MMP-2 or TIMP-2 mRNAs, and established several clones with various MMP-2:TIMP-2 expression ratios. On the basis of the quantitative evaluation of the MMP-2: TIMP-2 mRNA expression ratio by Northern blot analysis, we selected a clone overexpressing MMP-2 alone (RenCa/M), a clone overexpressing TIMP-2 alone (RenCa/T), and two kinds of clones overexpressing both, i.e., one with a high (RenCa/MTh) and one with a low (RenCa/MTl) MMP-2: TIMP-2 ratio, to compare the tumor cell phenotypes. In an in vitro tumor cell invasion assay, the MMP-2:TIMP-2 ratios of the RenCa sublines were directly correlated with their invasive potential. The invasive abilities of the parental RenCa cells induced by conditioned media from RenCa sublines were also correlated with the MMP-2:TIMP-2 ratios of the sublines. The cell adhesion assay showed the inverse correlation between the MMP-2 expression levels in the sublines and their cell adhesion to several extracellular matrix components. Furthermore, when injected i.v. or into the renal subcapsule in syngeneic mice, RenCa sublines formed metastatic nodules in the lungs, and the number of nodules was correlated with the MMP-2:TIMP-2 ratio of each clone. In contrast, despite the growth-inhibitory effects of TIMP-2 overexpression, MMP-2 overexpression had no effect on either proliferation in vitro of RenCa sublines or on their growth as tumors in vivo. These results suggest that the MMP-2:TIMP-2 expression ratio is a critical factor in the invasion and metastasis of renal cell carcinoma.

Animals↗
PubMed1999

[Comparison between indocyanine green angiography and outcome of surgical removal of choroidal neovascular membrane in age-related macular degeneration].

PURPOSE: To review the outcome of surgical removal of choroidal neovascular membranes in age-related macular degeneration as classified by indocyanine green angiographic findings. SUBJECTS AND METHOD: Surgery was performed in 42 eyes. They were divided into four types by indocyanine green angiographic findings prior to surgery. Type I comprised 29 eyes showing hyperfluorescence throughout the angiographic phases. Type II comprised 3 eyes showing hyperfluorescence during the early phase only. Type III comprised 5 eyes showing hyperfluorescence in the late phase only. Type IV comprised 5 eyes without hyperfluorescence throughout the angiographic phases. The results were evaluated according to the visual acuity expressed as log MAR before and after surgery. RESULTS: Visual acuity improved significantly in Types I, II, and III after surgery. Visual acuity did not improve in Type IV. CONCLUSION: The findings of indocyanine green angiography are thought to reflect the histological characteristics of the choroidal neovascular membrane. Neovascular membranes of Type IV may contain a smaller number of vessels and abundant fibrous tissue. Eye of Type IV will have atrophies in the neurosensory retina, retinal pigment epithelium, and choriocapillaris. Surgical removal of the choroidal neovascular membrane in Type IV is not effective in improving visual acuity.

Aged↗
PubMed1999

Azelastine N-demethylation by cytochrome P-450 (CYP)3A4, CYP2D6, and CYP1A2 in human liver microsomes: evaluation of approach to predict the contribution of multiple CYPs.

Azelastine, an antiallergy and antiasthmatic drug, has been reported to be mainly N-demethylated to desmethylazelastine in humans. In the present study, Eadie-Hofstee plots of azelastine N-demethylation in human liver microsomes were biphasic. In microsomes from human B-lymphoblast cells, recombinant cytochrome P-450 (CYP)2D6 and CYP1A1 exhibited higher azelastine N-demethylase activity than did other CYP enzymes. On the other hand, recombinant CYP3A4 and CYP1A2 as well as CYP1A1 and CYP2D6 in microsomes from baculovirus-infected insect cells were active in azelastine N-demethylation. The K(M) value of the recombinant CYP2D6 (2.1 microM) from baculovirus-infected insect cells was similar to the K(M) value of the high-affinity (2.4+/-1.3 microM) component in human liver microsomes. On the other hand, the K(M) values of the recombinant CYP3A4 (51.1 microM) and CYP1A2 (125.4 microM) from baculovirus-infected insect cells were similar to the K(M) value of the low-affinity (79.7+/-12.8 microM) component in human liver microsomes. Bufuralol inhibited the high-affinity component, making the Eadie-Hofstee plot in human liver microsomes monophasic. Azelastine N-demethylase activity in human liver microsomes (5 microM azelastine) was inhibited by ketoconazole, erythromycin, and fluvoxamine (IC(50) = 0.08, 18.2, and 17.2 microM, respectively). Azelastine N-demethylase activity in microsomes from twelve human livers was significantly correlated with testosterone 6beta-hydroxylase activity (r = 0.849, p<.0005). The percent contributions of CYP1A2, CYP2D6, and CYP3A4 in human livers were predicted using several approaches based on the concept of correction with CYP contents or relative activity factors (RAFs). Our data suggested that the approach using RAF(CL) (RAF as the ratio of clearance) is most predictive of the N-demethylation clearance of azelastine because it best reflects the observed N-demethylation clearance in human liver microsomes. Summarizing the results, azelastine N-demethylation in humans liver microsomes is catalyzed mainly by CYP3A4 and CYP2D6, and CYP1A2 to a small extent (in average, 76.6, 21.8, and 3.9%, respectively), although the percent contribution of each isoform varied among individuals.

Animals↗
PubMed1999

Role of human CYP2B6 in S-mephobarbital N-demethylation.

The role of cytochrome P-450s (CYPs) in S-mephobarbital N-demethylation was investigated by using human liver microsomes and cDNA-expressed CYPs. Among the 10 cDNA-expressed CYPs studied (CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4), only CYP2B6 could catalyze S-mephobarbital N-demethylation. The apparent K(m) values of human liver microsomes for S-mephobarbital N-demethylation were close to that of cDNA-expressed CYP2B6 (about 250 microM). The N-demethylase activity of S-mephobarbital in 10 human liver microsomes was strongly correlated with immunodetectable CYP2B6 levels (r = 0.920, p<.001). Orphenadrine (300 microM), a CYP2B6 inhibitor, inhibited the N-demethylase activity of S-mephobarbital in human liver microsomes to 29% of control activity. Therefore, it appears that CYP2B6 mainly catalyzes S-mephobarbital N-demethylation in human liver microsomes.

Anticonvulsants↗