Abstract:
:A total of 16 metabolites of bromocriptine could be isolated from rat bile and incubates of rat liver cell preparations using [6-methyl-14C]bromocriptine as substrate. Separation and purification was achieved by reversed-phase liquid chromatography and preparative thin-layer chromatography in conjunction with radioactivity monitoring. Structure elucidation was based on spectroscopic data (UV, IR, NMR, EI- and FD-MS) and the results of amino acid analysis after acid hydrolysis. Based on the identified metabolites four principal transformation process could be described: -Hydrolytic cleavage of the amide bridge leading to the formation of 2-bromolysergic acid amide (3) and 2-bromolysergic acid (7). -epimerization at position 8 of the bromolysergic acid moiety to the iso-derivatives (isobromocriptine, 2-bromo-isolysergic acid (6), its amide (1), etc.) -regiospecific oxidation at position 8' in the proline fragment generating stereoisomeric 8'-hydroxy-bromocriptines (21-24) -further oxidation of the 8'-hydroxylated derivatives by either the introduction of a second hydroxy group at position 9' to give dihydroxylated derivatives (detected as conjugates with glucuronic acid: metabolites 29, 30 and 31), or the opening of the proline ring under formation of the metabolites 4 and 5 containing glutamic acid instead of proline (7', 8'-seco- 8'-carboxy-bromocriptines). It is suggested that the primary and principal metabolic attack occurs at the proline fragment of the drug. In contrast to the biotransformation of ergoline compounds, none of the bromocriptine metabolites detected showed oxidative transformations in the lysergic acid half of the molecule.
journal_name
Eur J Drug Metab Pharmacokinetjournal_title
European journal of drug metabolism and pharmacokineticsauthors
Maurer G,Schreier E,Delaborde S,Loosli HR,Nufer R,Shukla APdoi
10.1007/BF03189631subject
Has Abstractpub_date
1982-10-01 00:00:00pages
281-92issue
4eissn
0378-7966issn
2107-0180journal_volume
7pub_type
杂志文章abstract::The aim of this study was to investigate by HPLC the in vivo metabolism of 2-[1'-phenyl-3'-(3-chlorophenyl)-2'-propenylyden]hydrazino-3-methyl-4(3H)-quinazolinone as a substrate, and as a model compound in rats. The substrate was dissolved in DMSO/water (1:4) and administered intraperitoneally at a dose of 100 mg/kg i...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03190629
更新日期:2005-10-01 00:00:00
abstract::The biotransformation of netobimin (NTB) pro-drug by ruminal, abomasal and intestinal fluids of sheep and cattle was investigated under anaerobic conditions in vitro. No metabolic conversion of NTB was observed upon incubation with abomasal fluid or boiled samples of different gastrointestinal fluids. NTB pro-drug was...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03188780
更新日期:1992-04-01 00:00:00
abstract::The metabolic fate of the anti-Parkinsonian drug budipine was studied in rats after oral administration. The presence of an aromatic hydroxylation product, metabolite M1, and its O-sulphate conjugate was confirmed. Three new minor metabolites, budipine N-oxide, metabolite M1 N-oxide and a secondary metabolite derived ...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03189947
更新日期:1991-04-01 00:00:00
abstract:BACKGROUND:Omadacycline is a semisynthetic aminomethylcycline antibacterial derived from the tetracycline class. It is approved in the USA to treat adults with acute bacterial skin and skin-structure infections and community-acquired bacterial pneumonia. OBJECTIVES:This phase I, open-label study evaluated the effect o...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s13318-020-00651-3
更新日期:2021-01-01 00:00:00
abstract::A comparative bioavailability study was undertaken between a new formulation of rifampicin 'Famcin' and a standard formulation of rifampicin 'R-cin' in eight healthy male volunteers at two dose levels: 300 mg and 450 mg given orally under both single dose and steady state conditions. Plasma rifampicin was assayed spec...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03189964
更新日期:1991-07-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Methyl 3,4-dihydroxybenzoate (MDHB) has the potential to prevent neurodegenerative diseases (NDDs). The present work aims to reveal the pharmacokinetics and tissue distribution characteristics of MDHB. METHODS:The pharmacokinetics and tissue distribution of MDHB were analyzed using LC-MS/MS a...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s13318-018-0512-8
更新日期:2019-04-01 00:00:00
abstract::The pharmacokinetic-pharmacodynamic (PK-PD) relationship of the proton pump inhibitor rabeprazole in healthy Chinese volunteers was characterized via a population approach. Healthy Chinese male volunteers were enrolled in the clinical trial. Subjects were divided into three groups by their CYP2C19 genotype. Serum conc...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03190639
更新日期:2006-01-01 00:00:00
abstract::In a single dose, randomized, cross-over study, with one week of wash-out period, the relative bioavailability of Dopegyt tablets containing 250 mg alpha-methyldopa (AMD) and Presinol film tablets with identical active ingredient content was examined in 24 healthy volunteers. Since technologically two completely diffe...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03190372
更新日期:2001-01-01 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:Lidocaine 5% medicated plaster is the first lidocaine containing product for chronic use. As no previous investigations have been conducted to evaluate the population pharmacokinetics of long-term exposure to lidocaine 5% medicated plasters, further insights into the evaluation of the pharmaco...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1007/s13318-017-0400-7
更新日期:2017-10-01 00:00:00
abstract::The hypoxic cell radiosensitizing drug, misonidazole (Miso) (Ro 07-0582) and its demethylated metabolite were administered to Wistar rats at different dose levels to examine their renal elimination. The data were consistent with a model in which Miso is eliminated mainly after biotransformation into desmethylmisonidaz...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03189740
更新日期:1985-07-01 00:00:00
abstract::Recent evidences suggest that genetic CYP2C19 polymorphism plays a role in the development of treatment resistance for clopidogrel's antiplatelet therapy. This short communication puts forward some strategies that could be potentially used to overcome the genetic polymorphism associated hurdles. While there is some es...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03191165
更新日期:2009-07-01 00:00:00
abstract::BACKGROUND AND OBJECTIVE: Efavirenz is commonly used in Africa and is frequently associated with neurocognitive toxicity, which may compromise clinical outcomes. Older individuals are at increased risk for drug toxicity and clinical outcomes may be worse in older age, particularly among those individuals with cytochro...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s13318-018-0507-5
更新日期:2019-04-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Ginseng is usually consumed as a dietary supplement for health care in the normal state or prescribed as a herbal medicine in pathologic conditions. Although metabolic studies of ginseng are commonly performed on healthy organisms, the metabolic characteristics in pathologic organisms remain un...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s13318-020-00645-1
更新日期:2021-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Doxorubicin plays an essential role in the treatment of paediatric cancers. Defining genotypes with a higher risk for developing anthracycline-induced cardiotoxicity could help to reduce cardiotoxicity. METHODS:Data originated from a phase II study assessing the pharmacokinetics of doxorubici...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s13318-019-00592-6
更新日期:2020-06-01 00:00:00
abstract::Weibull function C = Bts-1exp(-lambda ts) was used to describe plasma concentration-time data of ribavirin in 6 healthy subjects following an i.v. dose of 600 mg. A good fit was found in each of the subjects, where the coefficients of determination r2 were > 0.99. The parameters estimated were as follows: B, 5.90 +/- ...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03189718
更新日期:1996-07-01 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: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
abstract::Tectorigenin (Te) is a main active component in the flowers of Pueraria thomsonii Benth. and the rhizomes of Belamcanda chinensis (L.) DC. Previously, we have reported the pharmacokinetic properties of Te in rat plasma. The purpose of this study was to investigate the urinary excretion of Te after oral administration ...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s13318-014-0202-0
更新日期:2015-09-01 00:00:00
abstract::Influence of two newly synthesized bile acids derivates, namely sodium salt of monoketocholic acid MKH-Na and methyl ester of monoketocholic acid MKH-Me on tramadol (12.5 mg/kg oral and intramuscular) analgesic effect was examined in this research. Analgesic effect was measured by antinociceptive hot plate method. Int...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s13318-010-0011-z
更新日期:2010-09-01 00:00:00
abstract::Fluvastatin (FV), a new cholesterol-lowering agent, has been studied for its effects on hepatic microsomal drug-metabolizing enzymes in male rats. FV was orally administered in dosages of 1, 5, and 30 mg/kg/day for 7 consecutive days. 3-Hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase activities were markedly decrease...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03189669
更新日期:1995-07-01 00:00:00
abstract::The pharmacokinetics of tolbutamide (TB) have been studied in endotoxin pretreated rats with the aim of evaluating TB as a marker for endotoxin effects. Endotoxin dose of 10 mg/kg resulted in a 50% rate of mortality. TB was i.v. administered 24 h. after endotoxin dosing. Clearance (Cl) decreased by approximately 2/3 o...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03190205
更新日期:1990-07-01 00:00:00
abstract::The co-administration of lidocaine and propranolol leads to significant drug-drug interactions. Beta-blockers decrease liver perfusion and inhibit the activity of hepatic microsomal lidocaine metabolizing enzymes of the P450_2D subfamily. Hence, there is a resulting reduction in the hepatic breakdown of lidocaine and ...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03191006
更新日期:2007-10-01 00:00:00
abstract::Release rates from intramuscular and intra-adipose injection sites are dependent upon several including injection depth. Little is known about the relationship between drug lipophilicity and transport rate of drugs through adipose and muscle tissue. The principal objective of the present study was to investigate to wh...
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 aim of this study was to investigate the response of cortisol, insulin and lipid parameters [serum Lipoprotein Lipase activity, choleseryl-ester transfer protein, triglycerides, total Cholesterol, High Density Lipoprotein, Free Fatty Acids] during the perioperative period in obese patients undergoing laparoscopic ...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03190596
更新日期:2004-07-01 00:00:00
abstract::The effect of exogenous coenzyme Q10 (CoQ10) on the pharmacokinetic profiles and biliary excretion of doxorubicin and its main metabolites, doxorubicinol and doxorubicinolone, was investigated in rats. No statistically significant changes in the pharmacokinetic parameters of doxorubicin was observed following the intr...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03190456
更新日期:2002-07-01 00:00:00
abstract::Sertraline potently inhibits cytochrome P450 2B6 (CYP2B6) in vitro. Bupropion is commonly co-prescribed with sertraline and is exclusively metabolized by CYP2B6 to its major active metabolite hydroxybupropion. Putatively the co-administration of bupropion and sertraline could lead to a significant pharmacokinetic drug...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s13318-011-0065-6
更新日期:2012-03-01 00:00:00
abstract::This study investigated the effect of a commercial preparation of stevioside and a synthetic compound, sodium salt of monketocholic acid (MKC), administered per os (p.o.) and also adminstered via an osmotic pump, on glycemia in normoglycemic and diabetic Wistar rats. Diabetes was induced with alloxan, 100 mg/kg, i.p. ...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03191014
更新日期:2008-01-01 00:00:00
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...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s13318-012-0102-0
更新日期:2013-06-01 00:00:00
abstract::Previous studies have indicated that borneol has double side effects on the central nervous system (CNS), but the mechanism is unknown. The aim of this study was to clarify the relationship between excitation ratio [contents of excitatory amino acids (AAs) versus that of inhibitory] and the content of natural borneol ...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s13318-011-0058-5
更新日期:2012-03-01 00:00:00