Abstract:
BACKGROUND AND OBJECTIVES:Hydronidone is a novel pyridine derivative with therapeutic potential for hepatic fibrosis. The aim of this study was to investigate the safety, tolerability, and pharmacokinetics of hydronidone in healthy subjects. Effects of sex and food on hydronidone pharmacokinetics were also evaluated. METHODS:A randomized, dose-escalating, first-in-human study was conducted in 88 subjects. Five cohorts of 34 subjects received a single dose of hydronidone capsules at 15-120 mg, and two cohorts of 12 subjects received 90 and 120 mg of hydronidone thrice daily for 7 days, and six subjects received 60 mg of hydronidone thrice daily for 28 days to assess the safety and tolerability. In 36 subjects, hydronidone pharmacokinetics were investigated following oral administration of single (30, 60, and 120 mg) and multiple (60 mg, thrice daily) doses of hydronidone. RESULTS:Plasma concentrations of hydronidone and area under the concentration-time curve were found to be proportional to dose. Hydronidone was rapidly absorbed [median time to maximum plasma concentration (t max) = 0.33-0.63 h] and cleared [terminal elimination half-life (t 1/2) = 1.72-3.10 h]. Pharmacokinetic parameters after multiple doses were similar to those after single dose. Food had a significant affect (P < 0.01) on the extent and rate of absorption. No significant sex differences were noted for pharmacokinetic variables. CONCLUSION:Hydronidone was well tolerated and rapidly absorbed, and concomitant intake of food reduced rate and extent (about 20 %) of absorption in healthy volunteers. There was no accumulation following multiple doses of hydronidone. These results support a 60 mg thrice-daily regimen for management of hepatic fibrosis and further development of hydronidone (registered at ClinicalTrials.gov as ChiCTR-ONC-12002899).
journal_name
Eur J Drug Metab Pharmacokinetjournal_title
European journal of drug metabolism and pharmacokineticsauthors
Liu Y,Wu J,Li Z,Luo Y,Zeng F,Shi Sdoi
10.1007/s13318-015-0316-zsubject
Has Abstractpub_date
2017-02-01 00:00:00pages
37-48issue
1eissn
0378-7966issn
2107-0180pii
10.1007/s13318-015-0316-zjournal_volume
42pub_type
杂志文章,随机对照试验abstract::The influence of decreased albumin concentration on the pharmacokinetic behaviour of Piroxicam was studied in vivo in rats that had undergone plasmapheresis. Reductions of approximately 25% and 50% in the plasma albumin concentration were achieved, the former in rats not given plasma expander, the latter in animals gi...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03188792
更新日期:1993-04-01 00:00:00
abstract::Pomegranate juice (PJ) is known to be a potent inhibitor of human cytochrome enzymes. The purpose of this study was to investigate the effect of acute and chronic PJ on the pharmacokinetics of oral nitrendipine (10 mg/kg) in rabbits. Male New Zealand rabbits were pretreated with PJ for 1 week and on the last day, a si...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s13318-011-0075-4
更新日期:2012-06-01 00:00:00
abstract::The in vitro and in vivo metabolism of RWJ-69442, an alpha-1A-adrenergic receptor antagonist, was investigated after incubation with rat, dog, and human hepatic S9 fractions in the presence of NADPH-generating system, and a single oral/iv dose administration to rats (oral: 100 mg/kg; iv: 10 mg/kg). Unchanged RWJ-69442...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03226416
更新日期:2005-01-01 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: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::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::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 disposition kinetics of the N-oxide of picobenzide were studied after administration to rabbits at a bolus dose of 30 mg/kg of picobenzide intravenously. The biotransformation process fits a first-order kinetic process, and the metabolite shows good access capacity to the peripheral compartment. The N-oxide of pic...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03190837
更新日期:1989-01-01 00:00:00
abstract::Thymoquinone (THQ), the active constituent of Nigella sativa seeds, has demonstrated some potential pharmacological activities. The present study was designed to investigate the pharmacokinetic behavior of THQ following intravenous (IV) and oral (PO) administration using an animal model. THQ was given vascularly (5 mg...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s13318-014-0207-8
更新日期:2015-09-01 00:00:00
abstract::The disposition of the gonadotropin-releasing hormone (GnRH) agonist buserelin was studied in male rats under conditions of long-term administration. Rats were continuously infused with about 30 pmole [3H]-buserelin/24 h subcutaneously by osmotic minipumps for 4-7 days. After killing the rats, the 3H-activity of the t...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03189737
更新日期:1996-10-01 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::UDP-glucuronosyltransferase 1A9 (UGT1A9) contributes to the glucuronidation of numerous drugs. Cynomolgus monkeys are regarded as experimental animals similar to humans in studies on safety evaluation and biotransformation for drug development. In this study, the similarities and differences in the enzymatic propertie...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s13318-014-0177-x
更新日期:2014-09-01 00:00:00
abstract::The purpose of this study was to determine the distribution of cyclosporin A (CsA) in various ocular fluids and tissues in the rabbit by two routes of administration. CsA was administered to two groups of two rabbits either by intramuscular route at a dose of 25 mg/kg/day or by local route using eyedrops, at a dose of...
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::This study developed a physiologically based pharmacokinetic (PBPK) model in intraabdominally infected rats and extrapolated it to humans to predict the levofloxacin pharmacokinetics and penetration into tissues. Twelve male rats with intraabdominal infections induced by Escherichia coli received a single dose of 50 m...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s13318-015-0271-8
更新日期:2016-08-01 00:00:00
abstract:OBJECTIVE:By using a population pharmacokinetic analysis method, we predicted the efficacy of Ceftriaxone (CTRX) based on the pharmacokinetics of CTRX in Japanese adults and the sensitivity of infective organisms to CTRX in 2004. In addition, we clarified the difference in efficacy between once-a-day administration and...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03191159
更新日期:2009-04-01 00:00:00
abstract::10 healthy lactating women were treated orally with the anthelmintic praziquantel (Biltricide), and the resulting timedependent concentrations of the unchanged substance in plasma and milk were determined simultaneously. 5 of the women ("1st trial") received the single dose of 50 mg/kg; the other 5 women ("2nd trial")...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03189426
更新日期:1979-01-01 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::In this article, the methods of isolation and determination of bile acids are reviewed. Methods for separation of bile acids from cattle and pig bile are given in detail. Isolation of a mixture of cholic acid and deoxycholic acids from cattle bile and their subsequent purification are described. The isolation and puri...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章,评审
doi:10.1007/BF03190712
更新日期:2006-07-01 00:00:00
abstract::The aim of this work was to study the influence of labelling on caffeine metabolism according to the incubation mode. It has been observed that labelling induces an isotopic effect on metabolisation speed: apparent half-lives are systematically increased. Moreover, isotopic effects are in agreement with those previous...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03189795
更新日期:1997-04-01 00:00:00
abstract::Microcomputers have been used in pharmacokinetics for several years, but their use in the area of formulation is a new application. By using appropriate data on the drug, the dosage form required and its mechanism of absorption and clearance, microcomputers can systematize and speed-up formulation, simplify manufactur...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章,评审
doi:10.1007/BF03189611
更新日期:1984-04-01 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:BACKGROUND AND OBJECTIVES:Maximum plasma concentration of biopharmaceuticals sometimes occurs long after completion of intravenous infusion. The objective of this research was to study the hypothetical adsorption of biopharmaceuticals to endothelium and infusion material, which may theoretically explain this phenomenon...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s13318-017-0430-1
更新日期:2018-02-01 00:00:00
abstract::Lisofylline (LSF), is the R-(-) enantiomer of the metabolite M1 of pentoxifylline, and is currently under development for the treatment of type 1 diabetes. The aim of the study was to develop a physiologically based pharmacokinetic (PBPK) model of LSF in mice and to perform simulations in order to predict LSF concentr...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s13318-015-0260-y
更新日期:2016-08-01 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::This study investigated the effect of diltiazem on the bioavailability of oral and intravenous cyclosporine (CsA) in rats. While control rats received normal saline, experimental groups received 60 or 90 mg/kg diltiazem orally for 3 days. Each group divided into 2 equal groups that received a single oral dose or i.v. ...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03190586
更新日期:2004-04-01 00:00:00
abstract::A rapid and sensitive procedure is described for the quantitation of levamisole in plasma using high-performance liquid chromatography (HPLC). The procedure involves sample preparation using a reverse-phase C18 cartridge prior to chromatography and quantitation using peak area ratios (UV absorbance detection, 225 nm) ...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03226369
更新日期:1995-04-01 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: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::The liver first pass effect of pinazepam in four anaesthetized rabbits was determined by measuring the concentrations of this compound and those of its metabolite N-desmethyldiazepam in the plasma from the portal and hepatic veins. Anaesthesia was induced with an i.p. injection of urethane (1.5 g/kg). Portal and hepat...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03188728
更新日期:1982-01-01 00:00:00