Biomedical subjects

H H Zhou

Publications and source records attributed to H H Zhou.

At least 19 recordsLinked to original sources

PubMed2006

Preparation and electrocatalytic properties of Pt-SiO2 nanocatalysts for ethanol electrooxidation.

Due to their high stability in general acidic solutions, SiO(2) nanoparticles were selected as the second catalyst for ethanol oxidation in sulfuric acid aqueous solution. Pt-SiO(2) nanocatalysts were prepared in this paper. The micrography and elemental composition of Pt-SiO(2) nanoparticles were characterized by scanning electron microscopy and energy dispersive X-ray spectroscopy, respectively. The electrocatalytic properties of Pt-SiO(2) nanocatalysts for ethanol oxidation were investigated by cyclic voltammetry. Under the same Pt loading mass and experimental conditions for ethanol oxidation, Pt-SiO(2) nanocatalysts show higher activity than PtRu/C (E-Tek), Pt/C (E-Tek), and Pt catalysts. Additionally, Pt-SiO(2) nanocatalysts possess good anti-poisoning ability. The results indicate that Pt-SiO(2) nanocatalysts may have good potential applications in direct ethanol fuel cells.

Journal Article↗

PubMed2004

Pharmacokinetics and bioavailability of florfenicol following intravenous, intramuscular and oral administrations in rabbits.

This study examined the disposition kinetics and bioavailability of florfenicol after intravenous (i.v.), intramuscular (i.m.) and oral administration to rabbits at a dose of 30 mg/kg BW. Serial blood samples were collected through an indwelling catheter intermittently for 24 h for various routes. Plasma antibacterial concentrations were determined using a microbiological assay method with Bacillus subtilis ATCC 6633 as a reference organism. Plasma concentration-time data generated in the present study were analysed by non-compartmental methods based on statistical moment theory. Following i.v. administration, the overall elimination half-life (t1/2beta) was 1.54 h, mean residence time (MRT) was 1.69 h, mean volume of distribution at steady-state (Vdss) was 0.57 L/kg, and total body clearance (Cltot) was 0.34 L/kg/h. After i.m. and oral dosing, the terminal part of the curve should correspond to the absorption phase, instead of to the elimination phase, with terminal half-lives of 3.01 and 2.57 h, respectively. The mean absorption time (MAT) was 2.65 h for i.m. and 2.01 h for oral administration. Elimination rate constants differed with i.v., i.m. and oral administrations, suggesting a flip-flop situation. The observed mean peak plasma concentrations (Cmax obs) were 21.65 and 15.14 microg/ml achieved at a post-injection time (Tmax obs) of 0.5 h following i.m. and oral dosing, respectively. The absolute systemic availabilities were 88.25% and 50.79%, respectively, and the extent of plasma protein binding percent was 11.65%.

Administration, Oral↗

PubMed2004

Regularity of distribution of immunoreactive pulmonary surfactant protein A in rat tissues.

Existing data has shown that SP-A-like protein or mRNA is widely distributed in lamellar bodies such as tissues and mucosal surfaces. Using immunohistochemistry method with a polyclonal antibody against human SP-A, in this study we investigated distribution of immunoreactive pulmonary surfactant protein A (IR-SP-A) in a number of rat tissues. The SP-A-like immunoreactivity was found in alveolar, parenchyma, pleura of lung; myelin sheath of brain; epithelia of Bowman's capsule, glomerulus and renal tubules of kidney; epithelia of colon, stomach, duct of salivary gland, pharynx; and blood vessel wall and connective tissue of extracellular matrix. The positive signal was blocked by pre-absorbed SP-A antigen from recombinant or bronchoalveolar lavage (BAL). SP-A has long been considered as an important frontier host defense molecule which participates in immune and inflammatory regulation of lung. With every inhalation, small particles, viruses, bacteria, and antigens from environment are continuously deposited onto the vast pulmonary epithelial surface. While a proper host defense is required to protect the lung, an over-exuberant response can disrupt the appropriate balance between pro- and anti-inflammatory. Traditional Chinese medicine believes that body is an open system relevant to the external environment. The physical, chemical and biological environmental factors constantly affect the open system, and the body properly reacts to maintain homeostasis of body machinery. The Chinese traditional medicine scholars have thus hypothesized that 'Qi' (meaning air) is the communication way between the body and external environment. What is 'Qi'? The results from our study suggest that IR-SP-A is a candidate of 'Qi'. It is compatible with the sites, theoretically containing collagenous and lectin domain molecules, also compatible with the primary injury sites of some autoimmune diseases. SP-A may be as one of 'Qi' molecules mentioned in traditional Chinese medicine that trigger some of autoimmune diseases.

Animals↗

PubMed2001

CYP2C19 genotype determines enzyme activity and inducibility of S-mephenytoin hydroxylase.

BACKGROUND: The association between decreased drug clearance and decreased activity of cytochrome P4502C19 (CYP2C19), the inherited nature of the deficiency, and its frequency and clinical importance were evaluated extensively in the past over one decade. There is an interethnic difference in the frequency of poor metabolizers and mutant alleles of CYP2C19 among Chinese nationalities. Different frequency of mutations that code for CYP2C19 results in interethnic differences in distribution of the polymorphic trait for this enzyme. CYP2C19 genotype is a major determined factor for metabolisms of S-mephenytoin (S-MP), diazepam, and omeprazole (OP). The formations of their metabolites, 4'-hydroxymephenytoin (4'-OH-MP), demethyldiazepam, and 5-hydroxyomeprazole (5-OH-OP) are CYP2C19 genotype dependent. The inducibility of CYP2C19 activity is also related to CYP2C19 genotype. CONCLUSIONS: The availability of phenotyping and genotyping methods should help identify the adverse reaction and toxicity of drugs that metabolized by CYP2C19 and determine the doses of these drugs according to individual CYP2C19 genotype.

Aryl Hydrocarbon Hydroxylases↗

PubMed2001

Effect of the CYP2C19 oxidation polymorphism on fluoxetine metabolism in Chinese healthy subjects.

AIMS: The study was designed to investigate whether genetically determined CYP2C19 activity affects the metabolism of fluoxetine in healthy subjects. METHODS: A single oral dose of fluoxetine (40 mg) was administrated successively to 14 healthy young men with high (extensive metabolizers, n=8) and low (poor metabolizers, n = 6) CYP2C19 activity. Blood samples were collected for 5-7 half-lives and fluoxetine, and norfluoxetine were determined by reversed-phase high performance liquid chromatography. RESULTS: Poor metabolizers (PMs) showed a mean 46% increase in fluoxetine peak plasma concentrations (Cmax, P < 0.001), 128% increase in area under the concentration vs time curve (AUC(0, infinity), P < 0.001), 113% increase in terminal elimination half-life (t(1/2)) (P < 0.001), and 55% decrease in CLo (P < 0.001) compared with extensive metabolizers (EMs). Mean +/- (s.d) norfluoxetine AUC(0, 192 h) was significantly lower in PMs than that in EMs (1343 +/- 277 vs 2935 +/- 311, P < 0.001). Mean fluoxetine Cmax and AUC(0, infinity) in wild-type homozygotes (CYP2C19*1/CYP2C19*1) were significantly lower than that in PMs (22.4 +/- 3.9 vs 36.7 +/- 8.9, P < 0.001; 732 +/- 42 vs 2152 +/- 492, P < 0.001, respectively). Mean oral clearance in individuals with the wild type homozygous genotype was significantly higher than that in heterozygotes and that in PMs (54.7 +/- 3.4 vs 36.0 +/- 8.7, P < 0.01; 54.7 +/- 3.4 vs 20.6 +/- 6.2, P < 0.001, respectively). Mean norfluoxetine AUC(0, 192 h) in PMs was significantly lower than that in wild type homozygotes (1343 +/- 277 vs 3163 +/- 121, P < 0.05) and that in heterozygotes (1343 +/- 277 vs 2706 +/- 273, P < 0.001), respectively. CONCLUSIONS: The results indicated that CYP2C19 appears to play a major role in the metabolism of fluoxetine, and in particular its N-demethylation among Chinese healthy subjects.

Adolescent↗

PubMed2001

Effect of asymmetric dimethylarginine on osteoblastic differentiation.

BACKGROUND: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase (NOS) that accumulates in renal insufficiency and may be a uremic toxin. To determine whether ADMA inhibits bone metabolism, we investigated the in vitro effect of ADMA on osteoblastic differentiation in mouse bone marrow-derived mesenchymal stem cells (BMSCs). METHODS: The effect of ADMA on nitric oxide (NO) production was determined by measuring the stable end product of NO, nitrite, in the culture medium using commercial NO kit. The temporal sequence of osteoblastic differentiation in BMSCs was assessed in the presence and absence of ADMA by measuring alkaline phosphatase (ALP) activity, mineralization, and osteoblast gene expression at 0, 4, 8, 12 days of culture. RESULTS: ADMA (5, 50, 500 micromol. L-1) resulted in a dose-dependent decrease in nitrite formation in conditioned media of BMCS cultures, consistent with inhibition of NOS. ADMA treatment was associated with reduced ALP activity, calcium deposition and osteoblast-related gene expression in BMSCs cultures. Concurrent treatment with l-arginine (3600 micromol. L-1) reversed the ADMA (500 micromol. L-1)-mediated decrease in NO production, restored the differentiation potential of BMSCs, and significantly attenuated the down-regulation of Cbfa1 and osteocalcin gene expression by ADMA. CONCLUSIONS: ADMA inhibition of the NO-NOS pathway in BMSCs impairs osteoblastic differentiation of mouse BMSC cultures. These studies further support a role of NO in the local regulation of bone metabolism and the possibility that ADMA may act as uremic toxin on bone through its effect to inhibit NO actions in osteoblasts.

Alkaline Phosphatase↗

PubMed2001

Pharmacokinetics of sertraline in relation to genetic polymorphism of CYP2C19.

OBJECTIVE: Our objective was to evaluate the relationship between the disposition of sertraline and the presence of the CYP2C19 gene and to define the contribution of cytochrome P450 2C19 (CYP2C19) to sertraline N-demethylation. METHODS: A single oral 100-mg dose of sertraline was administered to 6 subjects who were extensive metabolizers and 6 subjects who were poor metabolizers recruited from 77 healthy Chinese volunteers whose genotypes were predetermined by polymerase chain reaction-based amplification, followed by restriction fragment length polymorphism analysis. Phenotypes were determined by use of the omeprazole metabolic rate. The plasma concentrations of sertraline and desmethylsertraline were determined by gas chromatography with electron-capture detection. RESULTS: Six poor metabolizers with m1 mutation had area under the plasma concentration versus time curve (AUC(0-infinity)) values (983.6 +/- 199.3 microg x h/L versus 697.6 +/- 133.0 microg x h/L; P <.05) and terminal elimination half-life values of sertraline (35.5 +/- 5.6 hours versus 23.5 +/- 4.4 hours; P <.01) that were significantly higher than the values in 6 extensive metabolizers who were either homozygous or heterozygous for CYP2C19*1. The oral clearance of sertraline in poor metabolizers (105.3 +/- 19.4 L/h) was significantly lower than that of extensive metabolizers (148.4 +/- 28.6 L/h). The area under the concentration-time curve from 0 to 144 hours and the maximum plasma concentration of desmethylsertraline in poor metabolizers were significantly lower than the values of extensive metabolizers (627.6 +/- 203.8 microg x h/L versus 972.1 +/- 270.3 microg x h/L; P <.05; and 23.6 +/- 6.5 nmol/L versus 32.4 +/- 8.2 nmol/L; P <.01; respectively). CONCLUSIONS: The polymorphic CYP2C19 appears to be a major enzyme involved in the N-demethylation of sertraline, and both extensive and poor metabolizers had marked differences in the disposition of sertraline.

Administration, Oral↗

PubMed2001

Assessment of cytochrome P450 activity by a five-drug cocktail approach.

OBJECTIVES: Our goal was to establish and validate a modified cocktail approach including probe drugs caffeine, chlorzoxazone, mephenytoin, metoprolol, and midazolam for simultaneous phenotyping of CYP1A2, CYP2E1, CYP2C19, CYP2D6, and CYP3A. METHODS: The study was conducted in 14 healthy, nonsmoking male volunteers with a cocktail of 5 drugs consisting of 100 mg caffeine, 200 mg chlorzoxazone, 100 mg mephenytoin, 100 mg metoprolol, and 7.5 mg midazolam in a randomized manner with a 7 x 7 Latin square design. Plasma was obtained at 1, 4, and 6 hours, and urine was collected from 0 to 8 hours after oral drug administration. RESULTS: The phenotypic indexes determined for caffeine, chlorzoxazone, mephenytoin, metoprolol, and midazolam were not significantly different when the drugs were given in different combinations. There were no metabolic interactions or analytic interference of these probe drugs. CONCLUSIONS: This cocktail approach can simultaneously provide independent in vivo phenotypic measures for the cytochrome P450 (CYP) enzymes CYP1A2, CYP2E1, CYP2C19, CYP2D6, and CYP3A.

Adult↗

PubMed2001

Transcranial electrical motor evoked potential monitoring for brain tumor resection.

OBJECTIVE: This study was designed to examine whether transcranial electrical motor evoked potential (MEP) monitoring is safe, feasible, and valuable for brain tumor surgery. METHODS: Fifty consecutive patients undergoing brain tumor resection were studied, using nitrous oxide/propofol anesthesia. MEPs were continuously recorded throughout surgery, using a Sentinel 4 evoked potential system (Axon Systems, Inc., Hauppauge, NY). The MEPs were elicited by transcranial electrical stimulation (train of 5; stimulation rate, 0.5-2 Hz; square wave pulse with a time constant of 0.5 ms; stimulation intensity, 40-160 mA) through spiral electrodes placed over the primary motor cortex and were recorded by needle electrodes inserted into the contralateral orbicularis oris, biceps, abductor pollicis brevis, and anterior tibialis muscles. When MEP amplitudes decreased by more than 50%, MEP stimulation was repeated, with increased stimulation intensity, and MEP changes were reported to the surgeon. The motor function of each patient was examined before and after surgery, using a reproducible scale. The relationship between MEP amplitude decreases and worsening motor status was analyzed using linear regression. RESULTS: Preoperative neurological examinations revealed mild to moderate motor deficits (2/5 to 4/5) for 38% of patients (19 of 50 patients). Most of the patients (96%) exhibited recordable baseline MEPs. Persistent MEP decreases of more than 50% were noted for eight patients (16%) (11 muscles). The MEPs were completely abolished in two patients (three muscles). The degree of postoperative worsening of motor status was correlated with the degree of intraoperative MEP amplitude reduction (r = -0.864; P < 0.001). CONCLUSION: Persistent intraoperative MEP reductions of more than 50% were associated with postoperative motor deficits. The degree of MEP amplitude reduction was correlated with postoperative worsening of motor status. Transcranial electrical MEP monitoring is feasible, safe, and valuable for brain tumor surgery.

Adolescent↗

PubMed2001

Arg389Gly beta 1-adrenoceptor polymorphism varies in frequency among different ethnic groups but does not alter response in vivo.

There are marked interethnic differences in beta 1-adrenoceptor-mediated responsiveness, with sensitivity decreased in African-Americans and increased in Chinese compared with Caucasians. Therefore, the frequency of a common naturally occurring polymorphism of the human beta 1-adrenoceptor gene (Arg389Gly), which has functional importance in vitro, was determined in 194 African-Americans, 316 Caucasian-Americans, 221 Hispanic-Americans and 142 Chinese. African-Americans were found to have a significantly lower frequency of the Arg389 allele than the other three ethnic groups (all P < 0.01). In the populations studied, the order of the distribution of the Arg389 allele was: Chinese (74%) > Caucasians (72%) > Hispanics (67%) > African-Americans (58%). To determine the functional significance of the Arg389Gly beta 1-adrenoceptor polymorphism, in-vivo heart rate responses to exercise were compared in healthy subjects homozygous for the Arg (n = 9) and Gly (n = 8) alleles. Heart rate response to exercise was not affected by genotype (P = 0.4). Although ethnic differences in the frequency of the beta 1-adrenoceptor Arg389Gly polymorphism exist, the polymorphism does not appear to have functional significance in healthy subjects and therefore may not contribute to ethnic differences in response to drugs acting through the beta 1-adrenoceptor.

Alleles↗

PubMed2001

Plasma caffeine metabolite ratio (17X/137X) in vivo associated with G-2964A and C734A polymorphisms of human CYP1A2.

Either G-2964 or A734 in the human CYP1A2 gene was confirmed to be associated with high inducible enzyme activity in smokers, but not in nonsmokers. In this study, for the first time, we observed an association between phenotypes and genotypes of CYP1A2 with respect to the two genetic polymorphisms in 163 healthy Chinese volunteers living in Qidong. The ratio of plasma 17X/137X at 6 h after oral administration of 300 mg caffeine was employed in CYP1A2 phenotyping analysis, while genotyping analysis was carried out by polymerase chain reaction-restriction fragment length polymorphism. The allele frequencies of A at -2964 and A at 734 in 139 non-smoking subjects were 0.25 and 0.67, respectively. The A/A-2964C/C734, G/A-2964C/C734 or A/A-2964C/A734 genotype that was thought to have lower inducibility/activity of CYP1A2 than the other genotypes did not exist in the tested Chinese subjects. The ratio of 17X/137X was 0.46 +/- 0.26 in G/G-2964A/A734 genotypes (n = 22) and 0.36 +/- 0.19 in non-G/G-2964A/A734 (n = 117). In addition, there was significant difference between them (P = 0.036). A similar result was also achieved in 24 smokers. Since Qidong is a special region with particularly high incidence of hepatocellular carcinoma in China, the association of phenotypes with genotypes of CYP1A2 in the Qidong population might result from some inducible environmental factors such as those of cigarettes in smokers.

Adult↗

PubMed2001

Effects of CYP2C19 genotype and CYP2C9 on fluoxetine N-demethylation in human liver microsomes.

AIM: The present study was designed to define the kinetic behavior of fluoxetine N-demethylation in human liver microsomes and to identify the isoforms of cytochrome P-450 (CYP) involved in this metabolic pathway. METHODS: The kinetics of Ne formation of norfluoxetine was determined in human liver microsomes from six genotyped CYP2C19 extensive metabolizers (EM). The correlation studies between the fluoxetine N-demethylase activity and various CYP enzyme activities were performed. Selective inhibitors or chemical probes of various cytochrome P-450 isoforms were also employed. RESULTS: The kinetics of norfluoxetine formation in all liver microsomes were fitted by a single-enzyme Michaelis-Menten equation (mean Km=32 micromol/L+/-7 micromol/L). Significant correlations were found between N-demethylation of fluoxetine at both 25 micromol/L and 100 micromol/L and 3-hydroxylation of tolbutamide at 250 micromol/L (r1=0.821, P1=0.001; r2=0.668, P2=0.013), respectively, and S-mephenytoin 4'-hydroxylase activity (r=0.717, P=0.006) at high substrate concentration of 100 micromol/L. S-mephenytoin (SMP) (a CYP2C19 substrate) at high concentration and sulfaphenazole (SUL) (a selective inhibitor of CYP2C9) substantially inhibited norfluoxetine formation. The reaction was minimally inhibited by coincubation with chemical probe, inhibitor of CYP3A4 (triacetyloleandomycin, TAO). The inhibition of fluoxetine N-demethylation at high substrate concentration (100 micromol/L) was greater in PM livers than in EM livers (73 % vs 45 %, P < 0.01) when the microsomes were precoincubated with SUL plus TAO. CONCLUSION: Cytochrome P-450 CYP2C9 is likely to be a major CYP isoform catalyzing fluoxetine N-demethylation in human liver microsomes at a substrate concentration close to the therapeutic level, while polymorphic CYP2C19 may play a more important role in this metabolic pathway at high substrate concentration.

Aryl Hydrocarbon Hydroxylases↗

PubMed2001

Role of cytochrome P450 in estradiol metabolism in vitro.

AIM: Catechol estrogens and 16alpha-hydroxy estrogen are important metabolites that cause carcinogenesis. This study was aimed to stud y the role of cytochrome P450 in estradiol metabolism. METHODS: The estradiol metabolites were determined with HPLC-ECD. Correlation of estradiol metabolites production between cytochrome P450 activity, the inhibitory effect of specific inhibitors and enzyme catalyzing kinetics were studied in cDNA-expressed P450 or human liver microsomes. RESULT: CYP1A2, CYP3A4, and CYP2C9 catalyze the estradiol 2-hydroxylation. CYP2C9, CYP2C19, and CYP2C8 have high activity in catalyzing 17beta-hydroxy dehydrogenation in cDNA expressed P450, but CYP1A2 is the most important enzyme in catalyzing estradiol 2-hydroxylation. Using furafyllin and troleandomycin to inhibit CYP1A2 and CYP3A4 in liver microsomes, it was found that the 2-hydroxylation had been inhibited about the same amount. This result suggests that in human liver microsomes CYP1A2 and CYP3A4 play an important role in 2-hydroxy estradiol formation. At low substrate concentration, 17beta -hydroxy dehydrogenation dominated the estradiol metabolism, but at high substrate concentration, 2-hydroxylation exceeded 17beta-hydroxy dehydrogenation to become the important mechanism. CONCLUSION: CYP1A2 and CYP3A4 are two important enzymes catalyzing the main estradiol 2-hydroxylation metabolism pathway at high substrate concentrations. 17beta-hydroxy dehydrogenation is the main metabolism pathway at low concentrations, and CYP2C9, CYP2C19, and CYP2C8 may have high catalyzing activity.

Adult↗

PubMed2001

Interindividual variations in levels and activities of cytochrome P-450 in liver microsomes of Chinese subjects.

AIM: To compare the level and/or activity of several important cytochrome P-450 (CYP) enzymes in liver microsomes prepared from different Chinese subjects. METHODS: Individual CYP contents, including CYP1A2, CYP2C9, and CYP3A4, in liver microsomes of 17 Han, 17 Zhuang, and 8 Miao subjects were determined by using Western blot analysis and densitometric scanning. The substrates for measuring the activity of individual CYP in vitro included phenacetin, tolbutamide, debrisoquine, and omeprazole. RESULTS: There was a large interindividual variability in the content and activity of CYP1A2, 2C9 and 3A4. And the activity of CYP2D6 also varied greatly between individual samples. CYP3A4 (32 %) is the most abundant CYP in Chinese liver microsomes, and the levels of CYP2C9 (19 %) and CYP1A2 (16 %) were also considerable. No clear ethnic, sex- and age-related differences in individual CYP content and catalytic activity were detected in 42 Chinese liver samples, except that there were somewhat ethnic and sex-related differences in the content and activity of CYP1A2. Good correlation between enzyme protein content and activity was found for CYP1A2, 2C9 and 3A4. CONCLUSION: Our results may provide useful information for the study of drug metabolism by liver microsomes in Chinese.

Aryl Hydrocarbon Hydroxylases↗

PubMed2001

Determination of estradiol metabolites in human liver microsome by high performance liquid chromatography-electrochemistry detector.

AIM: To constitute a method to determine the estradiol metabolites in human liver microsome in low concentration of estradiol. METHODS: Use high performance liquid chromatography after solvent extraction, evaporation, and reconstitution to separate the metabolites and use a electrochemistry detector to detect the metabolites. RESULTS: With a mobile phase of acetic acid buffer-acetonitrile (50:50, v/v, pH 4.5) at flow rate of 1.0 mL/min and a potential of +0.7 V vs Ag/AgCl, all six composition were well separated and satisfactorily detected. There are E3, 16alpha-OHE1, 2-OHE2, E1, and two unidentified composition. The minimum detectable amount is about 100 p g on column. This method is sensitive enough to detect E1 in a substrate concentration of 1 micromol/L. CONCLUSION: The method can be used to study the metabolism mechanism of estradiol in liver microsome.

Adult↗

PubMed2001

Single plasma sampling to predict oral clearance of CYP3A probe midazolam.

AIM: To find out a single plasma sampling to estimate oral clearance of midazolam (MDZ) and CYP3A activity, and explore the pharmacokinetics of midazolam hydroxylation in Chinese subjects. METHODS: The pharmacokinetics of midazolam was assessed in ten healthy male individuals after an oral dose of 7.5 mg midazolam. RESULTS: A significant correlation (r = 0.7, P < 0.05, n = 10) was found between plasma MDZ clearance and the plasma ratio of 1'-hydroxymidazolam to midazolam, which was assessed at 1 h after MDZ intake in the volunteers. Pharmacokinetics parameters of midazolam were as follows: Cmax (191 +/- 17) nmol/L, tmax (1.01 +/- 0.14) h, t(1/2) (3.2 +/- 0.4) h, AUC(0-infinity) (681 +/- 43) nmol.h.L-1), Cl(oral) (0.54 +/- 0.04) L.h-1.kg-1, Ke (0.2415 +/- 0.0021) h-1, Kalpha (0.82 +/- 0.18) h-1. CONCLUSION: Single plasma sampling of 1 h after 7.5 mg oral MDZ intake can be used to predict the oral clearance of midazolam.

Administration, Oral↗

PubMed2000

Phenotypic polymorphism and gender-related differences of CYP1A2 activity in a Chinese population.

AIMS: To investigate the distribution characteristics of CYP1A2 in a Chinese population, and to examine gender-related differences in CYP1A2 activity. METHODS: Two hundred and twenty-nine healthy subjects, 120 men and 109 women, were enrolled in this study. CYP1A2 activity was measured by plasma paraxanthine/caffeine (1,7X/1,3,7X) ratio 6 h after administration of 300 mg caffeine. The concentrations of paraxanthine and caffeine in plasma were detected by h.p.l.c. RESULTS: A 16-fold variation of CYP1A2 activity (range 0. 09 to 1.46) was shown in this study. The coefficient of variation (CV %) of CYP1A2 activity was 62.9%. Non-normal distribution of CYP1A2 activity was indicated by the Shapiro-Wilk test (P<0.001). Probit plots of CYP1A2 activity revealed a bimodal distribution with breakpoint of 1,7X/1,3,7X ratio of 0.12. The percentage of poor metabolizers (PMs) was 5.24% (95% CI: 2.35% approximately 8.13%) in this Chinese population. Residual analysis of the data also supported bimodality (P<0.01). The CYP1A2 activity of men was higher than that of women (median: 0.33 vs 0.23, P<0.001). A probit plot of CYP1A2 activity in men was shifted to the left compared with that in women. Based on phenotype, the gender-related difference was observed in extensive metabolizers (EMs) (P<0.001), but not in PMs (P >0.1). In addition, there was no sex-related difference in the incidence of PMs (P >0.1). CONCLUSIONS: There is a phenotypic polymorphism in CYP1A2 activity in this Chinese population, and CYP1A2 activity is higher in men than that in women.

Adolescent↗

PubMed2000

Comparison of isoflurane effects on motor evoked potential and F wave.

BACKGROUND: Volatile anesthetics produce surgical immobility by suppressing the motor system. The anesthetic action site in the motor pathway is unclear. Anesthetic effects on the whole and the lower portion of motor pathway can be studied by measuring the motor evoked potentials (MEP) and the F wave. This study measured the effect of isoflurane on the MEP and the F wave. METHODS: With institutional review board approval, we studied 12 adult patients with American Society of Anesthesiologists physical status I or II. After intubation, anesthesia was maintained with nitrous oxide/oxygen and propofol infusion. MEPs were elicited by transcranial electrical stimuli (train-of-five pulse; stimuli intensity 40-160 mA) through electrodes placed in the scalp at C3/C4 positions and recorded at the anterior tibialis muscle with an Axon Sentinel-4EP monitor. F waves were elicited by an electrode fixed over the posterior tibial nerve at the medial malleolus and recorded at the abductor hallucis muscle. After end-tidal concentration of isoflurane was maintained at 0.5% for 20 min, the MEP and F wave were measured again. MEP and F-wave changes before and after isoflurane were analyzed using paired Wilcoxon test with Bonferroni correction. The difference between the changes in MEP and F wave was analyzed using Friedman's test. RESULTS: Motor evoked potential amplitudes (median, 205 microV; 25th-75th percentiles, 120-338 microV), F-wave amplitude (median, 100 microV; 25th-75th percentiles, 64.2-137.5 microV), and F-wave persistence (59 +/- 29%) were decreased to 0 microV (0-15 microV), 49 microV (12.4-99.6 microV), and 30 +/- 31%, respectively, by 0.5% isoflurane. MEP amplitude suppression was different from the changes in F-wave amplitude and persistence (P < 0.02). CONCLUSIONS: Isoflurane 0.5% suppresses the motor pathway by decreasing both MEP and F wave. The MEP is suppressed more than the F wave.

Adult↗