Abstract:
:Astragalus injection (AI) and Astragalus granules (AG) are the two representative clinical preparations from Astragali Radix. In order to investigate the regulation of metabolism, AI and AG were tested for their ability to affect the major enzyme cytochrome P450 3A isoforms in vivo and in vitro. In the study of CYP3A1 enzyme activity, male rats were pretreated with AI and AG. The "cocktail" approach-based LC-MS/MS results showed that AI pretreatment at 0.16, 0.8 and 4 g kg(-1) day(-1) significantly increased the rat liver microsome CYP3A1 activity by 1.62-, 1.68- and 2.00-fold, and AG pretreatment at 32, 160 and 800 mg kg(-1) day(-1) significantly increased the rat CYP3A1 activity by 1.86-, 2.16- and 1.76-fold. The effects of AI and AG on liver microsome CYP3A1 mRNA expression in rats were analyzed using real-time PCR technique. The results showed that AI and AG pretreatments significantly increased the CYP3A1 mRNA expression. The induction of CYP3A4 enzyme activity by AI and AG in vitro was measured using a CYP3A4 luciferase reporter gene assay in transiently transfected human intestinal LS174T cells. Compared to the control group, AI at 62.5-1,000 mg/ml could significantly induce CYP3A4 reporter gene luciferase activity of 1.36- to 1.88-fold for 48-h incubated PXR-transfected LS174T cells, and AG at 62.5-1,000 μg/ml significantly transactivated CYP3A4 reporter gene luciferase activity of 1.36- to 2.05-fold. However, the CYP3A4 reporter gene construct was not significantly transactivated by the AI and AG in CAR-transfected LS174T cells. These CYP3A isoforms upregulation results can help us to use AI and AG rationally in the clinic.
journal_name
Eur J Drug Metab Pharmacokinetjournal_title
European journal of drug metabolism and pharmacokineticsauthors
Zhang Y,Huang L,Bi H,Cui Y,Li J,Wang X,Qin X,Chen J,Huang Mdoi
10.1007/s13318-012-0102-0subject
Has Abstractpub_date
2013-06-01 00:00:00pages
105-13issue
2eissn
0378-7966issn
2107-0180journal_volume
38pub_type
杂志文章abstract::Mathematical models that can predict the kinetics of compounds have been increasingly adopted for drug development and risk assessment. Data for these models may be generated from in vitro experimental systems containing enzymes contributing to metabolic clearance, such as subcellular tissue fractions including micros...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s13318-020-00666-w
更新日期:2020-12-19 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Polyethylene glycol-modified canine uricase (PEG-UHC) prepared with a lower-molecular-weight (5 kDa) PEG is used to treat gout. This study investigated the comparative pharmacokinetics of single and multiple doses of PEG-UHC administered intravenously and a single dose of uricase (UHC) administ...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s13318-020-00612-w
更新日期:2020-08-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Previous studies reported that tapentadol-sulfate represented one of the major metabolites of tapentadol excreted in urine. The current study aimed to identify the human cytosolic sulfotransferases (SULTs) that is(are) capable of sulfating tapentadol and to examine whether human cells and huma...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s13318-016-0392-8
更新日期:2017-10-01 00:00:00
abstract::The development of peptide therapeutics has increased enormously in recent decades. Many of the peptide drugs and antibody fragments that lack Fc backbone have a short half-life in circulation. In general, the half-life supports the design of the dosing regimen and frequency of administration, which are key aspects in...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s13318-020-00664-y
更新日期:2021-01-01 00:00:00
abstract::We studied the pharmacokinetics of moguisteine, a racemic non-narcotic peripheral antitussive drug, in 12 healthy male subjects after a single oral administration of 200 mg. The unchanged drug was absent in plasma and urine of all subjects. Moguisteine was immediately and completely hydrolyzed to its main active metab...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03190242
更新日期:1995-10-01 00:00:00
abstract::Because of its special pharmacokinetic properties, plasma levels of theophylline show significant differences between individuals and also its therapeutic index is very low. So, plasma theophylline concentration measurements are essential for an effective and safe treatment. In the present study, age related differenc...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF03188821
更新日期:1994-01-01 00:00:00
abstract::Apomorphine was administered subcutaneously and intranasally to 7 patients suffering from Parkinsonism with 'on-off' problems. This comparative pharmacokinetic study showed that the two routes of administration are comparable with respect to absorption kinetics. Apomorphine is rapidly absorbed when administered intran...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 临床试验,杂志文章
doi:10.1007/BF03192285
更新日期:1995-01-01 00:00:00
abstract:BACKGROUND:Experimental determination of a drug's oral bioavailability in humans is cost and time consuming; therefore, is usually performed on preclinical animals. It is believed that animal data are predictive of human data; however, there are some doubts regarding the reliability of this concept. The aim of this stu...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s13318-020-00636-2
更新日期:2020-12-01 00:00:00
abstract::It is known that substituted hydrazide hydrazone derivatives have several biological and pharmacological activities; there is limited literature on the metabolism of hydrazide hydrazones in rats. In our previous study, 4-fluorobenzoic acid [(5-nitro-2-furanyl)methylene]hydrazide (S) was found active against Staphyloco...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03190075
更新日期:2000-04-01 00:00:00
abstract::The antioxidant potential of a new flavonic derivative named conventionally theophylline-rutoside [TR-1722] was estimated by the measurement of G-6-Pase activity (marker enzyme for the endoplasmic reticulum), catalase activity (enzyme involved in the antioxidant defence process), and total -SH groups from the hepatic ...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03190270
更新日期:1996-01-01 00:00:00
abstract::The bioavailability of the recently developed 1 g dispersible tablet form of amoxicillin (B) and the 1 g dispersible tablet in suspension form (C) were compared to that of the 1 g standard reference formulation (A). Twelve healthy volunteers were involved in this single-dose, open, randomized, three-way cross-over stu...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF03189784
更新日期:1997-01-01 00:00:00
abstract::Two positional iodine derivatives of benzoic acid, i.e. ortho- (OIB) and para- (PIB), were used alone and in combination with salicylic acid (SA) to study the effects of plasma binding on their pharmacokinetics. Their lymphatic bioavailability (central lymph), their biotransformation and urinary excretion in rats were...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03188801
更新日期:1993-07-01 00:00:00
abstract::The disposition of a single 80 mg/kg injection of quinine base was compared in control and Plasmodium berghei-infected mice. Pharmacokinetic parameters were determined on repeated whole blood samples from caudal vein (experiment 1) and quinine distribution was evaluated in tissues and blood fractions from mice sacrifi...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03190862
更新日期:2003-01-01 00:00:00
abstract::The profile of urinary metabolites of 3H-arbaprostil was characterized in the male dog after intravenous administration. The major metabolites were purified and their structures deduced by gas chromatography/mass spectrometry (GC/MS) studies after conversion to the methyl ester-methoxime-trimethylsilyl ether derivativ...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03191312
更新日期:1988-04-01 00:00:00
abstract::The cardioselective beta-adrenergic blocking drug Visacor (ICI 141,292) was dosed to six beagle dogs in a randomized cross-over manner. Five formulations were examined i.e. a 15 mg/kg intravenous solution, a 50 mg/kg oral solution, and 50, 100 and 200 mg/kg oral powder formulations. Whole blood and urine samples were ...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03189616
更新日期:1984-04-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:The disposition of azithromycin in the human eye following topical administration has not been fully explored. Population pharmacokinetic (PopPK) modeling can allow useful conclusions to be drawn based on limited tear sampling data. The aim of this study was therefore to develop and evaluate a...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/s13318-018-0522-6
更新日期:2019-06-01 00:00:00
abstract::A multicompartmental pharmacokinetic model is presented, which based upon data from a previous study, describes the effects of ethanol (60 mM) on the metabolism of codeine (10 microM) in isolated rat hepatocytes. According to this model, about one third of codeine metabolized was transformed to morphine (13%) and norc...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03189852
更新日期:1986-07-01 00:00:00
abstract::The compound 4-amino-3-(3'-methoxycarbonyl-2'-thioureido) benzophenone has shown promise as a prodrug of the anthelmintic mebendazole. The compound is stable in acid and neutral media and is rapidly hydrolysed in base. An HPLC assay procedure for mebendazole, the prodrug and their known or expected metabolites and deg...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03188765
更新日期:1983-10-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Effective management of immunosuppressants is extemely important to improve prognosis of heart transplant recipients. We aim to investigate the effects of cytochrome P450 (CYP) 3A5 (rs776746) single nucleotide polymorphisms (SNPs) on serum tacrolimus concentrations/doses (C/Ds, ng/mL per mg/kg...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s13318-019-00563-x
更新日期:2019-12-01 00:00:00
abstract::Penbutolol is a not cardioselective beta-adrenergic blocking drug; it is lipid soluble and differs in its protein binding from the other members of its group because shows linkage to alpha 1-glycoprotein, with no detectable binding to albumin. AAG levels change during pregnancy and so the binding of [3H]-penbutolol wa...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03189924
更新日期:1988-01-01 00:00:00
abstract::Hepatic clearance of 3H-gitoxin was studied in the rabbit using an isolated perfused liver technique with an emulsion of a perfluorocarbon. The liposoluble material in the perfusion medium was extracted with dichloromethane, and gitoxin was assayed in the extract by high performance liquid chromatography. Pharmacokine...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03189704
更新日期:1985-04-01 00:00:00
abstract::YM466, a novel factor Xa inhibitor, is a hydrophilic compound with a carboxylic acid moiety. Previous studies in rats have shown that YM466 does nor undergo metabolism but is excreted into the bile and urine in unchanged form. Thus, in this study, we investigated in vivo hepatobiliary transport, focusing in particular...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03191128
更新日期:2006-04-01 00:00:00
abstract::COR3224 is a new 2-amino-2 oxazoline derivative with antidepressant properties. The distribution, excretion and metabolism of radiochemically labelled 14C-COR3224 has been investigated in the rat after intravenous injection. The compound was widely distributed and rapidly excreted. Hydroxylation and sulphate conjugati...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:
更新日期:1991-01-01 00:00:00
abstract::The fate of Ticlopidine, a new inhibitor of platelet aggregation, has been studied in rats following single oral doses. The compound was quickly absorbed as evaluated by the time of the peak plasma concentration. The metabolism of Ticlopidine involved N-oxidation, cleavage of the N-C bond, oxidation of aliphatic carbo...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03189474
更新日期:1981-01-01 00:00:00
abstract::The detection and the isolation in phenobarbital-induced rat liver microsomal incubation systems of a new metabolite of benzo(a)pyrene are described. The structure of this metabolite and the way in which it is formed are described. ...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03189442
更新日期:1980-01-01 00:00:00
abstract::Danirixin (GSK1325756) is a small, high-affinity, selective and reversible CXCR2 antagonist in development for treatment of chronic obstructive pulmonary disease. The objective of the study was to evaluate the relative bioavailability, including the inter-subject variability, of a conventional immediate-release (IR) f...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章,随机对照试验
doi:10.1007/s13318-014-0179-8
更新日期:2014-09-01 00:00:00
abstract::Hepatic transporters and metabolic enzymes affect drug pharmacokinetics. Limited information exists on the alteration in mRNA levels of hepatic transporters and metabolic enzymes with aging. We examined the effects of aging on the mRNA levels of representative hepatic drug transporters and metabolic enzymes by analyzi...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s13318-014-0208-7
更新日期:2015-06-01 00:00:00
abstract::The aim of the present study was to investigate the relative bioavailability and bioequivalence of a new tablet formulation of metformin hydrochloride with reference to a standard product in healthy Chinese adult male volunteers. Two randomized, comparative, two-way crossover studies were therefore conducted. In study...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章,随机对照试验
doi:10.1007/BF03190986
更新日期:2007-01-01 00:00:00
abstract::Herbal medicinal products have to meet comparable standards concerning the assessment of efficacy, safety and (bio)pharmaceutical quality as chemically defined synthetic drugs. However, these requirements are not fulfilled for many herbal products so far, particularly regarding in vitro dissolution and in vivo bioavai...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03190057
更新日期:2000-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Drug-drug interactions (DDIs) can occur when one drug alters the metabolism of another drug. Drug metabolism mediated by cytochrome P450 enzymes (CYPs) is responsible for the majority of metabolism of known drugs and inhibition of CYP enzymes is a well-known cause of DDIs. In the current study...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s13318-018-0485-7
更新日期:2018-12-01 00:00:00