The effect of aerobic exercise and Macrothele raven venom on tumor-bearing mice.

Liver cancer is one of the most common cancers in the world. Macrothele raven venom, a complicated mixture of neurotoxic peptides, proteins and low molecular weight material, has antitumor properties, but its mechanism of action is unknown. Moderate exercise has been shown to shrink tumors and cause a remarkable reduction in the tumor growth rate. In this study, we examined the antitumor effect of Macrothele raven venom in combination with exercise on tumor-bearing mice. Our results demonstrate that aerobic exercise in combination with venom administered at different doses was much more effective in a mouse H22 hepatoma model compared to separate administration of the 2 treatments. The underlying mechanism of this effect may be related to the expression of various tumor suppressor factors.

Intervention of TLR4 signal pathway cytokines in severe liver injury with obstructive jaundice in rats.

Obstructive jaundice is a common surgical disease and a variety of end-stage severe liver injuries still lack effective treatments. Compared to traditional liver transplantation therapy, herbal treatment is noninvasive and has fewer side effects. Research results have shown that a modified major decoction of bupleurum can reduce the toxic reaction of obstructive jaundice, even though the mechanism is unclear. A period of chronic exercise training can significantly reduce TLR4 expression in mononuclear cells and the secretion of inflammatory cell factors. Our study administered a modified major decoction of bupleurum in combination with exercise in rats with obstructive jaundice and the results indicated that applying a major bupleurum decoction in combination with moderately intense aerobic exercise showed a beneficial effect on adjusting the expression of liver inflammatory cytokines, which thus improved immunity and finally reduced the liver injury of rats with obstructive jaundice.

Stepwise regression analysis of the determinants of blood tacrolimus concentrations in Chinese patients with liver transplant.

Tacrolimus (FK506) is one of the immunosuppressive drugs used effectively to prevent allograft rejection after liver transplantation. Narrow therapeutic range and individual variance in pharmacokinetics make it difficult to establish a fixed dosage for all patients. Genetic polymorphism in drug metabolizing enzymes and in transporters may influence tacrolimus exposure. A stepwise regression analysis was used to analyze the relationship between blood concentrations of tacrolimus (54 blood samples at the day of 1 week, 2 week and one month after liver transplantation) and genetic & non-genetic factors in 18 Chinese liver transplant patients. The equation of multiple stepwise regression was: Y (tacrolimus' blood concentration) = 34.534 - 0.247 (age) - 0.510 (weight) + 1.688 (dose) + 6.876 (recipient's CYP3A5 genotype) - 3.097 (donor's CYP3A5 genotype), P < 0.01. The factors impacting patient's tacrolimus blood concentrations in a descending order are weight, recipient's CYP3A5 genotype, dose, age, donor's CYP3A5 genotype. Among those, patient's weight and recipient's CYP3A5 genotype could significantly impact the blood concentration of tacrolimus. The influence of recipient's CYP3A5 gene polymorphism is much more obvious than that of donor's. Neither donor's nor recipient's MDR1 genetic polymorphisms were correlated with the blood concentration of tacrolimus.

SO2 removal with ferric sulfate solution.

The determination of the influence of the concentration of ferric sulfate solution on SO2 absorption was performed in this study. It was found that the SO2 absorption efficiency increased with increasing ferric concentration, and decreased with the acidity of the spraying solution. As the hydrolysis of ferric ions occurs in solution, the SO2 removal efficiency increased slowly with increasing Fe(III) concentration. Taking into account the hydrodynamic and mass transfer characteristics of the packed column, the enhancement factor (E) was found to depend on the concentration of the ferric ions and pH, which indicated that it could be used for the simulation or design of SO2 scrubbers.

Biodegradation of methyl tert-butyl ether as a sole carbon source by aerobic granules cultivated in a sequencing batch reactor.

Aerobic granules efficient at degrading methyl tert-butyl ether (MTBE) were successfully developed in a well-mixed sequencing batch reactor (SBR). Treatment efficiency of MTBE in the reactor during the stable operations exceeded 99.8%, and effluent MTBE was consistently below 800 microg/L. The specific MTBE degradation rate was observed to increase with increasing MTBE initial concentrations from 25 to 400 mg/L, peaked at 18.2 mg-MTBE/g-VSS h, and declined with further increases in MTBE concentration as substrate inhibition effects became significant. There was a good fit between these biodegradation data and the Haldane equation (R (2) = 0.976). Microbial community DNA profiling was carried out using denaturing gradient gel electrophoresis (DGGE) of polymerase chain reaction amplified 16S rDNA. The aerobic granule was found to contain a wide diversity of microorganisms. More than 70% similarity among the samples in the time period examined indicated a highly stable microbial community as the reactor reached the stable operation.

Frequency of CYP2D6*10 and *14 alleles and their influence on the metabolic activity of CYP2D6 in a healthy Chinese population.

To study the frequency of CYP2D6(*)10 and (*)14 alleles in a healthy Chinese population, and the influence of these two alleles on the metabolic activity of CYP2D6. CYP2D6(*)10 and (*)14 genotypes of 295 healthy Chinese subjects were determined using a tetra-primer method and allele-specific amplification. CYP2D6 phenotypes of 131 subjects were determined using dextramethorphan as probe drug. There were 10 subjects with a (*)14 allele, including one homozygous for (*)14. The gene frequency of (*)10 and (*)14 alleles were 55.8 and 1.8%, respectively. The metabolic ratio (MR) of dextramethorphan in 131 subjects was 0.032+/-0.106. The MR of (*)1/(*)1, (*)1/(*)10, (*)10/(*)10, (*)1/(*)14, (*)10/(*)14, and (*)14/(*)14 groups were 0.007+/-0.012, 0.009+/-0.010, 0.042+/-0.029, 0.093, 0.11, and 1.186, respectively. The MR of subjects with (*)14 allele was higher than those of (*)1/(*)1, (*)1/(*)10, or (*)10/(*)10 groups (P<0.001). The CYP2D6(*)10 and (*)14 alleles have substantial impact on the metabolic activity of CYP2D6, and the CYP2D6(*)14 allele may be the cause of the poor metabolizer phenotype in Chinese subjects.

CYP2D6 genetic variation in healthy adults and psychiatric African-American subjects: implications for clinical practice and genetic testing.

Limited information is available on the frequency of the many CYP2D6 alleles found in African-Americans. DNA was isolated and genetic testing was performed on samples from 222 African-Americans, healthy controls (n=131), and psychiatric patients (n=91). Each DNA was tested for CYP2D6 alleles *2, *3, *4, *5, *6, *7, *8, *9, *10, *11, *14, *15, *17, *18, *19, *20, *25, *26, *29, *30, *31, *35, *36, *37, *40, *41 and *43 and 8 multiple copy alleles (*1xn, *2xn, *4xn, *41xn, *2Lxn, *17xn, *35xn and *10xn) using the AmpliChip CYP450 prototype microarray assay, along with allele-specific-PCR and PCR restriction fragment length polymorphism methods. No significant difference was noted between controls and psychiatric patients in any CYP2D6 allele frequencies. Three subjects were genotyped as poor metabolizers (1.4%; 0.0-2.9%, 95% confidence intervals (CI)), and 10 were classified as ultrarapid metabolizers (4.5%; 1.8-7.2%, 95% CI). A new CYP2D6 allele (*58) and two new duplicated CYP2D6 alleles (*17xn and *2Lxn) not previously reported were also identified. The frequency of the CYP2D6 overexpression in African-Americans may represent a greater therapeutic challenge than its deficiency based on these results. The most common alleles found in African-Americans including CYP2D6*1, *17 and *41 need to be investigated more closely for race-specific allelic variations and the mechanism responsible for differences in allele function more closely examined. The diversity of CYP2D6 alleles suggests that nucleotide arrays or similar methods are needed to efficiently test for the most prominent/relevant CYP2D6 alleles in humans.

Application of aerobic granular sludge in polishing the UASB effluent.

Stable aerobic granules were successfully developed in a sequencing batch reactor (SBR) fed with glucose and sodium acetate as the main carbon sources, and then they were acclimatized to polish the effluent from an up-flow anaerobic sludge blanket (UASB) reactor. It was found that more than 95% chemical oxygen demand (COD) and 85% suspended solids (SS) in the UASB effluent could be removed by an aerobic granular SBR as a post treatment unit. The performance of the SBR was stable over the whole experimental period. At an organic loading rate (OLR) of 4.5 to 5.4 g l(-1) d(-1), the acclimatized aerobic granules had an average diameter of 3.5 to 6.0 mm and a minimal settling velocity of 72 m h(-1). The biomass concentration in the SBR was as high as 8.4 g (dry weight) l(-1). This study showed for the first time that aerobic granular sludge in SBR would be an effective means to polish the effluent from UASB reactor.

The influence of pH on hydrolysis and acidogenesis of kitchen wastes in two-phase anaerobic digestion.

Batch and semi-continuous experiments were carried out to determine the effect of pH on hydrolysis and acidogenesis of kitchen wastes in the two-phase anaerobic digestion. The results of the batch experiment showed pH adjustment could improve both hydrolysis and acidogenesis rates of kitchen wastes. Compared with pH at 5, 9 and 11, pH 7 provided an optimum working condition for anaerobic digestion of kitchen wastes. At pH 7, about 86% of the total organic carbon (TOC) and 82% of chemical oxygen demand (COD) were solubilized and the maximum volatile fatty acid (VFA) concentration of 36 g l(-1) was achieved on the fourth day. The total VFA yield was 0.27 g (g total solid (TS))(-1), which almost doubled the yield without pH adjustment (0.15 g (g TS)(-1). The acidified products with lower concentration of lactic acid were more favorable to the subsequent methanogenesis. At pH 7, most of the protein was degraded into ammonia nitrogen (NH4(+)-N), resulting in additional buffer of acidified liquid. According to this, a novel method of pH adjustment applying NH4(+)-N buffer was established. The semi-continuous experiment indicated that adjusting pH to 7 in the acidogenic stage in the two-phase anaerobic digestion process would increase both TS loading rate (16g l(-1) d(-1)) and recovery of biological energy (520 ml methane (CH4) (g TS)(-1)).

Simultaneous modeling of pharmacokinetics and pharmacodynamics of propafenone in healthy subjects.

AIM: To study the simultaneous modeling of pharmacokinetics and pharmacodynamics (PK-PD) of propafenone (Pro) in healthy subjects. METHODS: Ten healthy Chinese volunteers, 5 extensive metabolizers (EM) and 5 intermediate metabolizers (IM) of CYP2D6, received a single dose (400 mg) of Pro hydrochloride. The blood samples and electrocardiogram (ECG) measurements were taken after administration over 15 h period. The concentrations of Pro in plasma were measured by a reverse-phase HPLC. PR interval was used as an average value of 10 PR interval measurements. RESULTS: There was a delay between Pro level and percentage of PR interval prolongation. After PK-PD simulating, the relationship between effect concentration (Ce) and the effect met the sigmoid E(max) model. CYP2D6 (EM & IM) played an important role in both pharmacokinetics and pharmacodynamics which produced by Pro. The AUC (microg . h . L-1) of IM group was significantly higher than that of EM group (5126 +/- 1030 vs 2948 +/- 1230, P < 0.05). Whereas Ce50 (microg/L) was also greater in IM group than in EM group (747 +/- 281 vs 359 +/- 123, P < 0.05). On the other hand, gamma of EM group was about one fold larger than that of IM group (P < 0.05). CONCLUSION: CYP2D6 phenotype of human may influence not only pharmacokinetic of Pro but also its pharmacological effects.

Isolation and Characterization of EDAG-1, A Novel Gene Related to Regulation in Hematopoietic System.

A novel gene, named embryonic develop associated gene 1 ( EDAG -1) and abundantly expressed in human fetal liver tissues, was isolated by screening a human fetal liver cDNA library and the 5' RACE. The full length of EDAG-1 mRNA is 2 166 bp, with an open reading frame of 1 452 bp neucleotides, encoding a 484 amino acid protein. No domain or motif was found similar with other genes by Blast program. Two copies of AUUUA motif in 3' non-translated region show instability of its mRNA. The molecular weight of the protein is 55.3 kD identified by the translation in vitro. EDAG-1 is specifically expressed in hematopoietic tissues, and is quickly down-regulated during the differentiation of K562 cells induced by hemin and EPO. These results show that EDAG-1 is related to the regulation in hematopoietic system and the development of leukemia.

Animal experiment and clinical study of effect of gamma-interferon on hepatic fibrosis.

AIM: To evaluate the antifibrotic effect of different doses of recombinant human Gamma-Interferon (IFN-gamma) in two rat models of hepatic fibrosis, and to observe its effect on moderate chronic hepatitis B virus fibrosis. METHODS: Hepatic fibrosis was successfully induced in 150 and 196 rats by subcutaneous injection of carbon tetrachloride (CCl4) and intraperitoneal injection of dimethylnitrosamine (DMN), respectively. Each of the two model groups was divided into: (1) fibrotic model group; (2) colchicine treatment group (0.1 mg/kg/day, gastrogavage for 8 weeks); (3) high-dose IFN-gamma group (15 MU/kg per day, i.m. for 8 weeks); (4) medium-dose IFN-gamma group (5 MU/kg daily, i.m. for 8 weeks); and (5) Y low-dose IFN-gamma group (1.67 MU/kg daily, i.m. for 8 weeks). Another group of 10 rats without any treatment was used as normal controls. At the end of the experiment, semi-quantitative histopathological scores of inflammation and fibrosis, liver alpha smooth muscle actin (alpha-SMA) expression level, liver hydroxyl proline content and serum hyaluronic acid levels were compared. And 47 medium chronic hepatitis B viral fibrosis patients were studied. They were given IFN-gamma treatment, 100 MU/day i.m. for the first three months and 100 MU qod i.m. for the next six months. Semi-quantitative pathological scores of inflammation and fibrosis and serum hepatic fibrosis indices were compared within the 9 months. RESULTS: In animal experiment, the pathological fibrosis scores and liver hydroxyl proline content were found to be significantly lower in rats treated with different doses of IFN-gamma as compared with rats in fibrotic model group induced by either CCl4 or DMN, in a dose-dependent manner. For CCl4-induced model, pathological fibrosis scores in high, medium and low doses IFN-gamma groups were 5.10 +/- 2.88, 7.70 +/- 3.53 and 8.00 +/- 3.30, respectively, but the score was 14.60 +/- 7.82 in fibrotic model group. Hydroxyl proline contents were 2.83 +/- 1.18, 3.59 +/- 1.22 and 4.80 +/- 1.62, in the three IFN-gamma groups, and 10.01 +/- 3.23 in fibrotic model group. The difference was statistically significant (P<0.01). Similar results were found in DMN-induced model. Pathological fibrosis scores were 6.30 +/- 0.48, 8.10 +/- 2.72 and 8.30 +/- 2.58, in high, medium and low doses IFN-gamma groups, and 12.60 +/- 3.57 in fibrotic model group. Hydroxyl proline contents were 2.72 +/- 0.58, 3.14 +/- 0.71 and 3.62 +/- 1.02, in the three IFN-gamma groups, and 12.79 +/- 1.54 in fibrotic model group. The difference was statistically significant (P<0.01). Serum hepatic fibrosis indices decreased significantly in the 47 patients after IFN-gamma treatment (HA: 433.38 +/- 373.00 vs 281.57 +/- 220.48; LN: 161.22 +/- 41.02 vs 146 +/- 35 +/- 44. 67; PC III: 192.59 +/- 89.95 vs 156.98 +/- 49.22; C-I: 156.30 +/- 44.01 vs 139.14 +/- 34.47) and the differences between the four indices were significant (P <0.05). Thirty-three patients received two liver biopsies, one before and one after IFN-gamma treatment. In thirty of 33 patients IFN-gamma had better effects according to semi-quantitative pathological scores (8.40 +/- 5.83 vs 5.30 +/- 4.05, P<0.05). CONCLUSION: All the three doses of IFN-gamma are effective in treating rat liver fibrosis induced by either CCl4 or DMN, the higher the dose, the better the effect. And IFN-gamma is effective for patients with moderate chronic hepatitis B viral fibrosis.

[Studies on synthesis and degradation of collagen at transcription level in liver fibrosis of rabbits with schistosomiasis japonica].

OBJECTIVE: To study the synthesis and degradation of collagen at the transcription level during liver fibrosis in rabbits with schistosomiasis japonica. METHODS: New Zealand rabbits infected with Schistosoma japonicum cercariae were served as animal models of liver fibrosis. The liver specimens were collected through operations at 4, 6, 8, 10, 12, 16, 20, 24 and 28 weeks after infection. Type I collagen, type III collagen, type IV collagen, MMP-1 and MMP-9 mRNA levels of liver tissue were detected by RT-PCR plus dot blotting, and the size of egg granulomas and the degree of liver fibrosis were measured by histopathological examinations. RESULTS: Type I collagen, type III collagen, type IV collagen, MMP-1 and MMP-9 mRNA levels increased simultaneously in the early stage after the infection, mostly reaching their peaks at 10 weeks after infection. Compared with normal controls, type I collagen, type III collagen, type IV collagen, MMP-1 and MMP-9 mRNA levels increased by 12.0-, 11.0-, 6.6-, 10.0- and 11.0-fold, respectively, coinciding with the changes of egg granulomas. Thereafter, both collagen and collagenase mRNA levels decreased. Types I, III and IV collagen mRNA levels declined to 2-fold to 3-fold compared with normal controls (P < 0.05), while MMP-1 and MMP-9 mRNA levels declined to normal level (P > 0.05) at 28 weeks. This study showed that the synthesis and degradation of collagen remained dynamic balance in the early stage of schistosomiasis, while in the later stage the metabolism of collagen synthesis was higher than that of collagen degradation. CONCLUSION: It was confirmed at the transcription level that when the metabolism of collagen synthesis was higher than that of collagen degradation in rabbits with schistosomiasis japonica, liver fibrosis might be produced.

[Dynamic changes in collagen type I and collagen type III in rabbits infected with Schistosoma japonicum and the effect of gamma-interferon].

OBJECTIVE: To observe the dynamic changes in collagen type I and collagen type III in rabbits with schistosomiasis japonica and the treatment effect of gamma-interferon on the degradation of collagens in schistosomal hepatic fibrosis. METHODS: Each rabbit was infected with 80 +/- 1 S. japonicum cercariae. Liver operations were done at different time points after infection and the liver specimens were embedded with paraffin and stained with alpha-SMA, HE and picric acid-Sirius red. The stained slides were observed under polarizing microscope and different collagen areas calculated by computer imagine analysis system. At the 16th week after infection, the infected rabbits received a single dose of praziquantel and gamma-interferon for 8 weeks. RESULTS: The area percent of collagen type I at the 28th week after infection (40.14 +/- 17.00) increased about seven fold compared with the 8th week group (5.73 +/- 3.40). The area percent of collagen type III at the 28th week after infection (6.80 +/- 5.19) increased about six fold compared with the 8th week group (1.15 +/- 1.34). The alpha-SMA positive cells also increased significantly. After gamma-interferon treatment, the area percent of collagen type I and type III decreased significantly, from 18.51 +/- 7.52 and 4.63 +/- 3.64 (before treatment) to 3.09 +/- 1.54 and 0.40 +/- 0.37 (0 and 4 weeks after treatment) (P < 0.01). However, after the withdrawl of gamma-interferon treatment, the collagen degradation was reversible. CONCLUSION: Gamma-interferon is effective in the treatment of hepatic fibrosis in rabbits infected with S. japonicum, the effect being reversible.

[Allele specific amplification for CYP2D6 gene related to intermediate metabolizer in Chinese subjects].

AIM: To establish an allele specific PCR amplification (ASA-PCR) for determination of the genotype of CYP2D6* 10B polymorphism in Chinese subjects. METHODS: CYP2D6* 10B alleles of 65 healthy Chinese subjects were analyzed by a two-step PCR assay and the correlation of genotype and phenotype was studied. RESULTS: There were 20 CYP2D6* 10B heterozygous genotypes subjects (wt/m) in 35 very extensive metabolizers (VEMs), which consisted the major part of VEM subjects (57%). Meanwhile, 20 subjects consisting 69% of 29 intermediate metabolizers were CYP2D6* 10B homozygous mutant genotypes (m/m). The poor metabolizer was also m/m. The metabolic ratio of CYP2D6* 10B m/m subjects were larger than wt/m and wild type, the values were -1.49 +/- 0.54, -2.20 +/- 0.49 and -2.47 +/- 0.61 (P < 0.01). CONCLUSION: PCR-ASA was shown to be a rapid and specific method. It can be used to study the genetic polymorphism, especially CYP2D6 intermediate metabolism.

[Derivative gas chromatographic analysis of fructooligosaccharide in fermented sucrose].

As a new sweetener, fructooligosaccharide is paid more and more attention for its health improvement property. It includes trisaccharide, tetrasaccharide and pentasaccharide, and can be produced from sucrose by the fermentation of microorganism. In order to analyze the content of fructooligosaccharide in fermented sugar by gas chromatography, fructooligosaccharide was transformed into trimethylsilyl derivatives. Based on the modified gas chromatograph SP2308, and under the chosen chromatographic conditions with 0.53 mm capillary column of OV-101, the contents of fructose, glucose, sucrose and fructooligosaccharide were determined by programmed temperature chromatography. The recovery of fructooligosaccharide was satisfactory.

[Peroxidase isoenzymes analysis on some plants under simulated microgravity].

The detection technology of peroxidase isoenzyme pattern were adopted in the study of the effect of simulated microgravity on some plants. Biochemical analysis indicated that the microgravity samples displayed an increased activity of peroxidase.

Fluoxetine impairs the CYP2D6-mediated metabolism of propafenone enantiomers in healthy Chinese volunteers.

OBJECTIVE: To determine the effect of 20 mg/day fluoxetine on the pharmacokinetics of propafenone enantiomers and CYP2D6 activity by phenotyping with dextromethorphan. METHODS: Nine healthy Chinese volunteers (seven men and two women) were included in a two-phase study. Dextromethorphan (20 mg) was given before and after subjects took 20 mg/day fluoxetine for 10 days, and the dextromethorphan metabolic ratio was calculated to determine CYP2D6 phenotype. Pharmacokinetic studies of propafenone enantiomers after a single oral 400 mg dose before and after pretreatment with 20 mg/day fluoxetine for 10 days were also conducted in these subjects. Reversed-phase HPLC with precolumn derivatization was used to determine enantiomeric concentrations of propafenone in plasma. RESULTS: Mean CYP2D6 dextromethorphan metabolic ratios before and after fluoxetine therapy were 0.028 +/- 0.031 and 0.080 +/- 0.058, respectively (P = .001), indicating that a strong inhibition of CYP2D6 by fluoxetine activity was observed in Chinese subjects. Propafenone metabolism was also impaired significantly after fluoxetine treatment. The elimination half-life, peak concentration, and area under the curve from 0 hours to infinity of two enantiomers after fluoxetine therapy were significantly increased compared with those at baseline (P < .01), whereas oral clearance decreased from 75.01 +/- 17.69 L/h to 49.36 +/- 8.62 L/h for S-propafenone (P = .005) and from 107.62 +/- 33.82 L/h to 70.60 +/- 12.42 L/h for R-propafenone (P = .027). In addition, fluoxetine increased the peak concentration of S-propafenone by 39% and that of R-propafenone by 71% (P < .05). A significant increase of the time to reach peak concentration was observed only in the R-enantiomer and not in the S-enantiomer of propafenone after fluoxetine therapy. There were no differences in the percentage changes of PR and QRS intervals before or after fluoxetine pretreatment at the time observed (P > .05). CONCLUSION: We conclude that fluoxetine may cause significant inhibition of the CYP2D6 activity as determined by dextromethorphan phenotyping. This inhibition impairs the metabolism of propafenone enantiomers in Chinese subjects. Caution must be exercised when fluoxetine and propafenone are coadministered to avoid potential toxicity.

The influence of CYP2D6 activity on the kinetics of propafenone enantiomers in Chinese subjects.

AIMS: To determine role of CYP2D6 activity in the pharmacokinetics of propafenone (PPF) enantiomers in native Chinese subjects. METHODS: Sixteen extensive metabolizers (EMs) and one poor metabolizer (PM), whose phenotype had been previously assessed with dextromethorphan metabolic phenotyping, were enrolled. Blood samples (0 approximately 15 h) were taken after oral administration of a single dose (400 mg) of racemic-propafenone hydrochloride. A reverse-phase h.p.l.c. method with pre-column derivatization was employed to quantitate enantiomeric concentrations of propafenone in plasma. RESULTS: For the EM subjects, S-PPF was less rapidly metabolized and had higher peak plasma concentrations than R-PPF (413+/-143 vs 291+/-109 ng ml-1, P<0.001). The AUC was markedly higher for S-PPF than for R-PPF (2214+/-776 vs 1639+/-630 microg h l-1, P<0.001), whereas the clearance of S-PPF was significantly lower than that of R-PPF (96.0+/-39.0 vs 138+/-78 l h-1, P<0.01). There were no differences in t1/2, and Cmax between the two isomers (P >0.05). In the one PM subject, not only did S-PPF appear to undergo less rapid metabolism than R-PPF, but the subject also showed 2 approximately 3 fold differences in Cmax, CL and AUC compared with EMs. The correlation coefficients (rs ) between dextromethorphan metabolic ratio (lg MR) and pharmacokinetic parameters (Cmax, CL and AUC) were 0.63, -0.87, 0.87 for S-PPF and 0. 57, -0.73, 0.86 for R-PPF, respectively. CONCLUSIONS: Our results suggest that CYP2D6 activity contributes to the pharmacokinetic variability of propafenone enantiomers in Chinese subjects.