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Biomedical subjects

Moses S S Chow

Publications and source records attributed to Moses S S Chow.

At least 19 recordsLinked to original sources
PubMed2006

Evaluation of HO-1-u-1 cell line as an in vitro model for sublingual drug delivery involving passive diffusion--Initial validation studies.

The aim of this study was to provide preliminary validation of a new sublingual mucosal cell line (HO-1-u-1) for use as in vitro sublingual drug delivery screening of compounds involving passive diffusion. HO-1-u-1 cells were seeded on cell culture inserts. The ultrastructure and integrity of cell layers, inter-passage variation and directionality of drug transport, and apparent permeability coefficient (P(app)) of eight beta-blockers (representing compounds involving passive diffusion) were determined. HO-1-u-1 cells grown on inserts formed stratified and epithelial-like structure and maintained the typical histological features of normal human sublingual epithelium. The maximal integrity of the cell layer was reached in 23 days. No significant inter-passage variation was found at the passages ranging from 2 to 11 when measured by radiolabeled transcellular and paracellular markers (testosterone and mannitol, respectively). Bidirectional transport studies confirmed the passive diffusion as the mechanism of transport for these markers. The P(app) of eight beta-blockers across HO-1-u-1 cell culture ranged from 2.89+/-0.17 to 6.37+/-0.37x10(-6)cm/s and correlated well to the P(app) obtained from porcine sublingual mucosa (r(2)=0.647 and 0.83 when excluding propranolol). The above results indicate that the HO-1-u-1 cells grown on inserts may offer as a potentially in vitro model for screening sublingual drug permeation involving passive diffusion.

Administration, Sublingual↗
PubMed2006

Phenotype-genotype relationship and clinical effects of citalopram in Chinese patients.

Although the relationship of CYP2C19 polymorphism to citalopram disposition has been studied in healthy subject, this relationship in combination with dynamic effects (clinical adverse effect of citalopram) has not been well studied in patients. We carried out the present study to investigate the CYP2C19 genotype-phenotype relationship and potentially relate such relationship to the clinical effect (specifically adverse effects) of citalopram in Chinese patients who are known to have relatively high prevalence of poor metabolizers (PMs) of CYP2C19. Fifty-three Chinese adult patients were recruited. One to 2 blood samples at 4 to 24 hours postdose were collected after a minimum of 2 weeks of citalopram administration. The CYP2C19 genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism, and the plasma concentrations of citalopram and desmethylcitalopram were determined by a liquid chromatography-tandem mass spectrometry method. The clinical adverse effects associated with citalopram were assessed according to Toronto Side Effects Scale (TSES). A population pharmacokinetic model was used to analyze the citalopram concentrations. Among 53 patients, 21 were homozygous extensive metabolizers (EMs) (CYP2C19*1/*1), 25 heterozygous EMs (CYP2C19*1/*2 or *1/*3), and 7 PMs (CYP2C19*2/*2 or *2/*3 or *3/*3). The metabolic ratios (plasma concentration of desmethylcitalopram to citalopram) were found to be 0.20 +/- 0.07, 0.15 +/- 0.05, and 0.07 +/- 0.03 in the homozygous EMs, heterozygous EMs, and PMs, respectively (P < 0.001, 1-way analysis of variance). On the basis of the results from our population pharmacokinetic modeling analysis, the citalopram oral clearances in the PMs were 42.9% and 33.3% (both P < 0.05) lower compared with the homozygous and heterozygous EMs, respectively. Statistically significant correlation was observed between the oral clearance and TSES scores in individual patients (rs = -0.37, P = 0.012). The mean TSES score also tended to be higher in PM than EM patients, but the difference was not statistically significant (P = 0.234). The study demonstrated a significant CYP2C19 genotype-phenotype relationship in Chinese patients receiving citalopram treatment. Such a relationship also tended to correlate with the clinical adverse effects of the drug. These results provide important pharmacogenetic implications for citalopram therapy in the Chinese population in whom relatively high frequency of CYP2C19 PM phenotype exists.

Administration, Oral↗
PubMed2006

Variability in renal clearance of substrates for renal transporters in chinese subjects.

The authors evaluated the inter- and intraindividual variability in the renal clearance of substrates of organic anion transporters (OAT) or organic cation transporters (OCT) using repeated drug application procedures. Two OAT substrates (ampicillin and cephalexin) and 2 OCT substrates (famotidine and metformin) were selected. Each drug was administered orally twice to healthy subjects, with sample sizes ranging from 12 to 28 (using bioequivalent formulations of each drug). The inter-(delta(inter)) and intrasubject (delta(intra)) variances in renal clearance were estimated based on analysis of variance, and the genetic contribution (r(GC)) was calculated as (delta(inter - intra))/delta(inter). The renal clearances of ampicillin, cephalexin, famotidine, and metformin averaged 5.21 (range, 2.87-11.20), 3.01 (range, 1.50-3.82), 4.96 (range, 2.84-8.17), and 9.44 (range, 5.66-15.43) mL/min/kg, with mean intraindividual coefficients of variation of 17.7%, 7.3%, 13.5%, and 9.0% and r(GC) values of 0.75, 0.89, 0.81, and 0.93, respectively. These high r(GC) values suggest a potential significant genetic contribution by the renal OATs and OCTs in Chinese subjects. Further studies in a larger population are needed to confirm the importance of these results as well as to identify specific genetic variants in these transporters responsible for such variability.

Adult↗
PubMed2006

Effect of the co-occurring components from green tea on the intestinal absorption and disposition of green tea polyphenols in Caco-2 monolayer model.

This study aimed to investigate the effect of co-occurring components from green tea on the intestinal absorption and disposition of green tea polyphenols (GTPs) using the Caco-2 cell monolayer model. The absorption and secretion transport of the four GTPs, in the form of individual pure compounds, pure compound mixtures and green tea extract, were studied in the Caco-2 cell model. Four GTPs and their metabolites were analysed by HPLC/MS and HPLC coupled with electrochemical detector. The apparent permeability coefficients (P(app)) of each compound, as well as the metabolites (mainly sulfation and methylation conjugates) generated, were compared for the different dosing formulations utilized. The results showed that the absorption transport of the four GTPs in different dosing formulations was similar. However, the secretion transport profiles of (-)-epicatechin (EC), (-)-epigallocatechin (EGC) and (-)-epigallocatechin gallate (EGCG) were altered when the GTP mixture was administered. It was suggested that transporter competition resulting in reduced efflux of EC, as well as metabolic competition resulting in reduced formation of EGC sulfate and methylated EGC sulfate, might be involved during the secretion transport of GTP mixture.

Biological Transport↗
PubMed2006

Population pharmacokinetics of cyclosporine in chinese cardiac transplant recipients.

STUDY OBJECTIVE: To characterize the population pharmacokinetics of cyclosporine in Chinese patients undergoing cardiac transplantation and to identify the demographic and clinical covariates affecting cyclosporine clearance. DESIGN: Population pharmacokinetic analysis using data from a retrospective chart review. SETTING: Specialty hospital in Hong Kong for treatment of cardiac and pulmonary diseases. PATIENTS: Thirty-eight Chinese adult patients (mean age 46 yrs) who had undergone routine cyclosporine therapeutic drug monitoring after cardiac transplantation between January 1, 1991, and December 31, 2003. MEASUREMENTS AND MAIN RESULTS: Data regarding dosing, demographics, clinical laboratory values, and concurrent drugs were collected retrospectively. Data were included if patients had blood cyclosporine concentrations determined for at least 12 weeks after transplantation; an average of 18 blood samples/patient were collected. Population modeling was performed using a one-compartment linear model with first-order absorption and elimination. Various demographic and clinical covariates were tested for their significant effects on the apparent oral clearance (Cl/F) of cyclosporine. The stability of the final population model was evaluated by using the bootstrap resampling method. Statistically significant associations were observed between Cl/F and each of the following covariates: body weight (BW), use of diltiazem (DIL), and hematocrit value (HCT). The final model was Cl/F=5.00*(1-DIL)+365/HCT+(0.144*BW). The interindividual variabilities of Cl/F and apparent volume of distribution were 14.5% and 40.2%, respectively. The mean parameter estimates obtained from bootstrap analyses were highly consistent with those obtained with the original data set. CONCLUSION: The estimated Cl/F values of cyclosporine in our Chinese cardiac transplant recipients appeared to be similar to those reported for Caucasian cardiac transplant recipients. Thus, our data provide support that a cyclosporine dosage regimen similar to that in Caucasian patients may be needed in Chinese cardiac transplant recipients. However, further studies are required to determine the optimum cyclosporine dosage regimen in the Chinese population.

Adult↗
PubMed2005

Pharmacokinetics and modeling of quercetin and metabolites.

PURPOSE: To determine the pharmacokinetics of quercetin and its glucuronide/sulfate conjugates and to develop a pharmacokinetic model to simultaneously describe their disposition after intravenous and oral administration in rats. METHODS: After oral, intraportal, and intravenous administration of quercetin, serial plasma, urine, and fecal concentrations of quercetin and its conjugates were determined by an HPLC method. Enterohepatic recirculation was evaluated in a linked-rat model as well as after oral administration of bile containing quercetin and its metabolites. Based on the experimental data, a specific compartmental model was developed and validated to describe and predict the plasma concentration-time profiles of quercetin and its conjugates after oral and intravenous administration. RESULTS: Only 5.3% of unchanged quercetin was bioavailable, although the total quercetin absorbed was as high as 59.1%. After oral administration, about 93.3% of quercetin was metabolized in the gut, with only 3.1% metabolized in the liver. No significant enterohepatic recirculation was observed for both quercetin and its conjugated metabolites. The pharmacokinetic model fitted well the observed data of quercetin and its conjugates. CONCLUSIONS: Our study clarifies the relative importance of the gut, liver, and bile in the metabolism and excretion of quercetin and its conjugates. The pharmacokinetic model appears to be suitable for describing the absorption and disposition of the quercetin and its conjugates and may be applicable to other flavonoids that undergo similar pharmacokinetic pathways.

Administration, Oral↗
PubMed2005

Effect of cyp2d6*10 allele on the pharmacokinetics of loratadine in chinese subjects.

Loratadine is known to be a substrate for both CYP3A4 and CYP2D6 based on a previous in vitro study. In view of the large interindividual variability in loratadine pharmacokinetics and the greater genetically determined variability of CYP2D6 activity than of CYP3A4 in vivo, we hypothesized that CYP2D6 polymorphisms may contribute to the pharmacokinetic variability of loratadine. The purpose of this study was to evaluate the effect of CYP2D6 genotype (specifically the CYP2D6*10 allele) on the pharmacokinetics of loratadine in Chinese subjects. Three groups of healthy male Chinese subjects were enrolled: group I, homozygous CYP2D6*1 (*1/*1, n=4); group II, heterozygous CYP2D6*10 (*1/*10 or *2/*10, n=6); and group III, homozygous CYP2D6*10 (*10/*10, n=7) carriers. Each subject received a single oral dose of 20 mg of loratadine under fasting conditions. Multiple blood samples were collected over 48 h, and the plasma concentrations of loratadine and its metabolite desloratadine were determined by high-performance liquid chromatography. In comparing homozygous CYP2D6*10 (group III) to heterozygous CYP2D6*10 (group II) to homozygous CYP2D6*1 (group I) subjects, loratadine oral clearance values were 7.17+/- 2.54 versus 11.06+/-1.70 versus 14.59+/-2.43 l/h/kg, respectively [one-way analysis of variance (ANOVA), p<0.01], and the corresponding metabolic ratios [area under the plasma concentration-time curve (AUC)(desloratadine)/AUC(loratadine)] were 1.55+/-0.73 versus 2.47+/- 0.46 versus 3.32+/- 0.49, respectively (one-way ANOVA, p<0.05), indicating a gene-dose effect. The results demonstrated that CYP2D6 polymorphism prevalent in the Chinese population significantly affected loratadine pharmacokinetics.

Adult↗
PubMed2005

Physicochemical and structural characterization of quercetin-beta-cyclodextrin complexes.

Quercetin is a bioactive flavonoid widely used as a health supplement. Being sparingly soluble and chemically unstable in aqueous intestinal fluids, quercetin is poorly absorbed orally. This study aimed to investigate the effects of three beta-cyclodextrins, namely, unsubstituted beta-cyclodextrin (beta-CD), hydroxypropyl-beta-cyclodextrin (HP-beta-CD), and sulfobutyl ether beta-cyclodextrin (SBE-beta-CD) on the chemical stability and water solubility of quercetin, and to elucidate the complexation mechanisms of these beta-CDs with quercetin. Quercetin-beta-CD complexes in solution were characterized by stability assessment, phase solubility measurements, and 1H-nuclear magnetic resonance (NMR) spectroscopy. Molecular modeling was used to help establish the mode of interaction of the beta-CDs with quercetin. Solubility enhancements of quercetin obtained with the three beta-CDs followed the rank order: SBE-beta-CD > HP-beta-CD > beta-CD. The stability of quercetin at alkaline pHs also showed substantial improvement. NMR spectroscopic analysis suggested that the B-ring, C-ring, and part of the A-ring of quercetin display favorable interaction with the hydrophobic cavity of the beta-CDs, which was confirmed by molecular dynamics (MD) simulations using a solvated model of the quercetin-beta-CD complex. An inclusion complex model has been established for explaining the observed augmentation of solubility and stability of quercetin in water by beta-CDs.

Chemical Phenomena↗
PubMed2005

Simultaneous determination of paracetamol and dextropropoxyphene in human plasma by liquid chromatography/tandem mass spectrometry: application to clinical bioequivalence studies.

A liquid chromatography/mass spectrometry method for simultaneous determination of paracetamol and dextropropoxyphene in human plasma is described. Paracetamol and dextropropoxyphene, together with their internal standards (tolbutamide and pyrroliphene), were extracted from 0.5 mL of plasma using solid-phase extraction. The chromatography was performed using a Thermo Hypersil APS-2 Amino column (250 mm x 4.6 mm, 5 microm) with a mobile phase consisting of acetonitrile and 0.4% glacial acetic acid in water (20:80). The total run time was 6 min for each sample. The triple-quadrupole mass spectrometer was operated in both positive (for detection of dextropropoxyphene and its IS pyrroliphene) and negative (for detection of paracetamol and its IS tolbutamide) modes using a polarity-switching technique. Multiple reaction monitoring was used for quantification. The method was linear over the concentration range of 0.1-20 microg/mL for paracetamol and 0.5-80 ng/mL for dextropropoxyphene. The intra- and inter-day precision were less than 10%, and the accuracy ranged from 92.2-110.9%. The lower limits of quantification were 0.1 microg/mL for paracetamol and 0.5 ng/mL for dextropropoxyphene. The present method provides a robust, fast and sensitive analytical tool for both paracetamol and dextropropoxyphene, and has been successfully applied to a clinical bioequivalence study in 14 subjects.

Acetaminophen↗
PubMed2005

CYP2C9, but not CYP2C19, polymorphisms affect the pharmacokinetics and pharmacodynamics of glyburide in Chinese subjects.

BACKGROUND: Although cytochrome P450 (CYP) 2C9 was thought to be the main pathway for glyburide (INN, glibenclamide) metabolism in vivo, studies in vitro indicated that CYP2C19 had a more dominant effect. This study investigated the relative influence of CYP2C9 and CYP2C19 genotypes on the pharmacokinetics and pharmacodynamics of glyburide in Chinese subjects. METHODS: Three groups of healthy male Chinese subjects (n=6 per group) were enrolled, as follows: group I, CYP2C9*1/*1 and CYP2C19 extensive metabolizers (EMs); group II, CYP2C9*1/*1 and CYP2C19 poor metabolizers (PMs); and group III, CYP2C9*1/*3 and CYP2C19 EMs. Subjects received single oral doses of 5 mg glyburide. Multiple blood samples were collected, and the plasma glyburide concentrations were determined by an HPLC method. The plasma glucose and insulin concentrations were also measured up to 2 hours after dosing. RESULTS: No significant differences in glyburide pharmacokinetics were observed between CYP2C19 EM and PM subjects who had the CYP2C9*1/*1 genotype (group I versus group II). Their respective values for area under the plasma concentration-time curve from time 0 to infinity (AUC0-infinity) and elimination half-life (t1/2) were 0.46+/-0.13 microg.h/mL versus 0.57+/- 0.11 microg.h/mL (P=.569) and 2.09+/-0.22 hours versus 2.24+/- 0.27 hours (P=.721). However, significant increases in AUC(0-infinity) (125% and 82%; P=.008 and .024, respectively) and t1/2 (71% and 60%; P=.003 and .007, respectively) were observed when CYP2C9*1/*3 subjects (group III) were compared with CYP2C9*1/*1 subjects in group I or II. Blood glucose reductions at 2 hours after dosing were 41.8%, 23.9%, and 27.7% in groups I, II, and III, respectively (P=.029), and hypoglycemia developed in 3 of 6 CYP2C9*1/*3 carriers and 2 of 12 CYP2C9*1/*1 carriers. CONCLUSION: CYP2C9, but not CYP2C19, polymorphism appears to exert a dominant influence on glyburide pharmacokinetics and pharmacodynamics in vivo. Further studies in diabetic patients with long-term dosing are warranted to confirm these findings.

Adult↗
PubMed2005

Difference in absorption of the two structurally similar flavonoid glycosides, hyperoside and isoquercitrin, in rats.

The present study was to investigate oral absorption of the two similar flavonoid glycosides, isoquercitrin (IQ, quercetin-3-O-glucoside) and hyperoside (HP, quercetin-3-O-galactoside) in rats. Two groups of male SD rats received an oral dose of either IQ (4.5 mg/kg) or HP (6.0 mg/kg). Blood samples were collected via jugular vein at time intervals after drug administration and the plasma concentrations of the studied compounds were analyzed by HPLC. The stability of IQ and HP in the GI tract was also measured by incubation with various GI contents from rats. The results showed that unchanged IQ was barely detectable whereas the glucuronidated quercetin (the aglycone of IQ) was found to be the major form in plasma after oral administration of IQ. In contrast, HP could not be detected in plasma neither as unchanged form nor its aglycone or conjugated aglycone form. Additional in vitro stability studies demonstrated that HP is more stable than IQ in the GI tract. This suggests that IQ could be hydrolyzed easier than HP to its aglycone in GI tract before being absorbed. In conclusion, IQ, as a flavonoid glucoside, could be rapidly absorbed and transformed into glucuronidated quercetin and such absorption might be related to the hydrolysis of the type of sugar moieties attached to its aglycone molecule.

Animals↗
PubMed2005

Comparison of the pharmacokinetics of hawthorn phenolics in extract versus individual pure compound.

The pharmacokinetics of an active herbal substance may be different when administered in an extract form as compared to that when administered as a pure compound. This study investigated the pharmacokinetics of 4 active compounds of hawthorn fruits--namely, (-)-epicatechin, chlorogenic acid, hyperoside, and isoquercitrin--following administration of an extract formulation (as hawthorn phenolic extract, which contained the active compounds) or equivalent doses of individual pure compound in male Sprague-Dawley rats (n = 5 per group). The hawthorn phenolic extract or pure compounds were administered both orally and intravenously. Following administration, multiple plasma samples were obtained, and the plasma concentrations were determined by high-performance liquid chromatography. After the intravenous injection of hawthorn phenolic extract, higher plasma drug concentration, larger area under the plasma concentration-time curve from 0 to infinity, longer terminal elimination half-life, smaller apparent volume of distribution, lower total body clearance, and higher urinary excretion of each compound were obtained when compared to that after the pure compound. Following the oral administration of either hawthorn phenolic extract or pure compound, only epicatechin was absorbed, and their pharmacokinetics were generally not significantly different between these 2 formulations. The differences in the pharmacokinetics of the 2 formulations following intravenous but not oral administration may be attributable to the existence of other co-occurring components in the hawthorn phonolic extract (which may be present in the body after intravenous but not oral administration). The results showed that an herbal extract formulation, when administered intravenously, could potentially alter the pharmacokinetics of its active ingredients.

Administration, Oral↗
PubMed2004

Investigation of intestinal absorption and disposition of green tea catechins by Caco-2 monolayer model.

The current study was designed to investigate the absorption mechanism and identify the possible disposition pathways of green tea catechins (GTC), including epicatechin (EC), epigallocatechin (EGC), epicatechin gallate (ECG) and epigallocatechin gallate (EGCG), during their absorption across small intestine by Caco-2 monolayer model. The transport of each GTC from both apical to basolateral and basolateral to apical directions was measured in the absence and the presence of MK571, an MRP inhibitor. HPLC and LC/MS were employed to identify the possible metabolites of the four GTC formed during their bidirectional transport processes. The results indicated that the four GTC showed limited transepithelial absorption with relatively small P(app) values. However, significant efflux mediated by MRP was observed during the secretion of GTC, especially the non-gallated catechins. Methylation and sulfation were the main biotransformation pathways of GTC during their secretion transport and the efflux of the related metabolites seem to be mediated by MRP.

Biological Transport↗
PubMed2004

Liquid chromatography-tandem mass spectrometry method for the determination of tranexamic acid in human plasma.

A new method for the determination of tranexamic acid (TA) in human plasma using high performance liquid chromatography with tandem mass spectrometric detection was described. TA and the internal standard, methyldopa, was extracted from a 200 l plasma sample by a one-step deproteination using perchloric acid. Chromatographic separation was performed on an Xtrra MS C18 Column (2.1 mm x 100 mm, 3.5 microm) with the mobile phase consisting of 10% acetonitrile in 2 mM ammonium acetate buffer (pH 3.5) at a flow rate of 0.15 ml/min. The total run time was 5 min for each sample. Detection and quantitation was performed by the mass spectrometer using the multiple reaction monitoring of the precursor-product ion pair m/z 158 --> 95 for TA and m/z 212 --> 166 for methyldopa, respectively. The method was linear over the concentration range of 0.02-10.00 g/ml with lower limit of quantification of 0.02 microg/ml for TA. The intra- and inter-day precision was less than 11% and accuracy ranged -10.88 to 11.35% at the TA concentrations tested. The present method provides a relatively simple and sensitive assay with short turn-around time. The method has been successfully applied to a clinical pharmacokinetic study of TA in 12 healthy subjects.

Calibration↗
PubMed2004

Rapid determination of five probe drugs and their metabolites in human plasma and urine by liquid chromatography/tandem mass spectrometry: application to cytochrome P450 phenotyping studies.

A liquid chromatography/mass spectrometry method, for rapid determination of five cytochrome P450 (CYP) probe drugs and their relevant metabolites in human plasma and urine, is described. The five specific probe substrates/metabolites, caffeine/paraxanthine (CYP1A2), tolbutamide/4-hydroxytolbutamide/carboxytolbutamide (CYP2C9), omeprazole/5-hydroxyomeprazole (CYP2C19), debrisoquine/5-hydroxydebrisoquine (CYP2D6) and midazolam/1'-hydroxymidazolam (CYP3A), together with the internal standards (phenacetin and paracetamol), in plasma and urine, were extracted using solid-phase extraction. The chromatography was performed using a C18 column with an isocratic mobile phase consisting of acetonitrile and 0.1% formic acid in water (70:30). The triple-quadrupole mass spectrometer was operated in both positive and negative modes, and multiple reaction monitoring was used for quantification. The method was validated over the concentration ranges 0.05-5 microg/mL for caffeine and paraxanthine, 0.02-2 microg/mL for tolbutamide, 0.1-20 microg/mL for 4-hydroxytolbutamide, carboxytolbutamide, debrisoquine and 5-hydroxydebrisoquine, 5-2500 ng/mL for omeprazole and 5-hydroxyomeprazole, and 1-100 ng/mL for midazolam and 1'-hydroxymidazolam. The intra- and inter-day precision were 0.3-13.7% and 1.9-14.3%, respectively, and the accuracy ranged from 93.5-107.2%. The lower limit of quantification varied between 1 and 100 ng/mL. The present method provides a robust, fast and sensitive analytical tool for the five-probe drug cocktail, and has been successfully applied to a clinical phenotyping study in 16 subjects.

Chromatography, High Pressure Liquid↗
PubMed2004

Differential effect of Coriolus versicolor (Yunzhi) extract on cytokine production by murine lymphocytes in vitro.

Being one of the commonly used Chinese medicinal herbs, Coriolus versicolor (CV), also named as Yunzhi, was known to possess both anti-tumor and immunopotentiating activities. The present study aimed to investigate the in vitro immunomodulatory effect of a standardized ethanol-water extract prepared from CV on the proliferation of murine splenic lymphocytes using the MTT assay, and the production of six T helper (Th)-related cytokines using the enzyme-linked immunosorbent assay (ELISA) technique. The results showed that the CV extract significantly augmented the proliferation of murine splenic lymphocytes in a time- and dose-dependent manner, maximally by 2.4-fold. Moreover, the production of two Th1-related cytokines, including interleukin (IL)-2 and IL-12, in culture supernatants from the CV extract-activated lymphocytes was prominently upregulated at 48 and 72 h. Positive correlations were found between the levels of these two cytokines and the MTT-based proliferative response. In contrast, the production of two other Th1-related cytokines, including interferon (IFN)-gamma and IL-18, was significantly augmented only at 24 h, but not at 48 and 72 h. On the other hand, the levels of two Th2-related cytokines such as IL-4 and IL-6 were undetectable in the culture supernatants of lymphocytes treated with the CV extract. The CV extract was suggested to be a lymphocyte mitogen by differentially enhancing the production of Th1-related cytokines.

Animals↗
PubMed2004

Pharmacogenetics and herb-drug interactions: experience with Ginkgo biloba and omeprazole.

OBJECTIVE: Ginkgo biloba was found to exert a significant inductive effect on CYP2C19 activity. This study was designed to investigate the potential herb-drug interaction between G. biloba and omeprazole, a widely used CYP2C19 substrate, in subjects with different CYP2C19 genotypes. METHODS: Eighteen healthy Chinese subjects previously genotyped for CYP2C19 were selected. All subjects received a single omeprazole 40 mg at baseline and then at the end of a 12-day treatment period with G. biloba (140 mg, bid). Multiple blood samples were collected over 12 h, and 24 h urine was collected post omeprazole dosing. Plasma and urine concentrations of omeprazole and its metabolites, 5-hydroxyomeprazole and omeprazole sulfone, were determined, and their pharmacokinetics calculated non-compartmentally. RESULTS: Plasma concentrations of omeprazole and omeprazole sulfone were significantly decreased, and 5-hydroxyomeprazole significantly increased following G. biloba administration in comparison to baseline. A significant decrease in the ratio of area under the plasma concentration-time curve (AUC) of omeprazole to 5-hydroxyomeprazole was observed in the homozygous extensive metabolizers, heterozygous extensive metabolizers, and poor metabolizers, respectively. The decrease was greater in PMs than EMs. No significant changes in the AUC ratios of omeprazole to omeprazole sulfone were observed. Renal clearance of 5-hydroxyomeprazole was significantly decreased after G. biloba, but the change was not significantly different among the three genotype groups. CONCLUSION: Our results show that G biloba can induce omeprazole hydroxylation in a CYP2C19 genotype-dependent manner and concurrently reduce the renal clearance of 5-hydroxyomeprazole. Co-administration of G. biloba with omeprazole or other CYP2C19 substrates may significantly reduce their effect, but further studies are warranted.

Adult↗