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 collected at various times after each dose and analysed for parent drug concentration by a high pressure liquid chromatography procedure. The urine samples were also analysed for parent drug content after hydrolysis with beta-glucuronidase. The normalised intravenous blood levels of ICI 141,292 were found to decay tri-exponentially with a final phase elimination half-life of about 10 h. The computer fitted data showed the drug to possess a high volume of distribution for both the central compartment (54% body weight) and whole body (1384% body weight) indicating the possibility of a high degree of metabolism. The drug clearance following i.v. administration was 196 ml/min and the urinary recovery rate of parent drug was 24% (unhydrolysed) and 40% following hydrolysis with beta-glucuronidase. Following oral dosing at 50 mg/kg (as both powder (C) and solution (B], 100 (D) and 200 (E) mg/kg (as powder) the systemic blood profiles were found to increase with dose. The mean peak blood level attained was 6 +/- 1, 5 +/- 1, 8 +/- 1 and 14 +/- 1 micrograms/ml for formulations, B, C, D and E respectively. The systemic bioavailability of ICI 141,292 was only about 40%. The areas under the curves increased linearly with dose and the elimination phase half-life was unchanged with dose. The calculated half-life (7 h) was apparently shorter after oral administration than after intravenous administration (10 h) but this is probably an artefact dependent on the limit of detection of the assay procedure. At 50 mg/kg there were no significant differences in blood profiles or in the urinary excretion of drug between the solution and powder formulations. However the overall systemic bioavailability was marginally higher with the powder. These observations are consistent for a drug which is cleared by both renal and hepatic elimination processes, which undergoes "first-pass" metabolism on oral dosing and, over the oral dose range studied, obeys linear pharmacokinetics. The significant increase in recovery of parent drug, after hydrolysis of the urine with beta-glucuronidase, indicates that the ICI 141,292 glucuronide conjugate is present to a significant extent. The results also demonstrate that absorption of parent drug from the gastrointestinal tract may not be complete.
journal_name
Eur J Drug Metab Pharmacokinetjournal_title
European journal of drug metabolism and pharmacokineticsauthors
McAinsh J,Smith RP,Ferguson RAdoi
10.1007/BF03189616subject
Has Abstractpub_date
1984-04-01 00:00:00pages
129-39issue
2eissn
0378-7966issn
2107-0180journal_volume
9pub_type
杂志文章abstract::Diabetes mellitus is becoming an increasingly prevalent disease that concerns patients and healthcare professionals worldwide. Among many anti-diabetic agents in clinical uses, numerous reports are available on their altered pharmacokinetics because of changes in the expression of drug transporters and metabolic enzym...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章,评审
doi:10.1007/s13318-015-0306-1
更新日期:2016-06-01 00:00:00
abstract::Six healthy volunteers received the same oral dose of doxycycline, base (200 mg). Each received two of the three preparations at two-week intervals. Experimental results were interpreted on the basis of one or two-compartment models. The three preparations gave the elimination constants of the same order of magnitude ...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03189510
更新日期:1981-01-01 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: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::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::A bioequivalence study compares the bioavailability between a test and a reference drug product in terms of the rate and extent of drug absorption. Area under the plasma concentration-time curve (AUC) and maximum plasma concentration (Cmax) are the pharmacokinetic parameters that serve as characteristics for the asses...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03190024
更新日期:1999-07-01 00:00:00
abstract::The transdermally applied dopamine receptor agonist rotigotine is extensively metabolized in the liver. An open-label, parallel-group study was conducted to evaluate the effects of moderate hepatic impairment on the pharmacokinetics, safety and tolerability of rotigotine. Eight subjects with normal hepatic function an...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章,多中心研究
doi:10.1007/s13318-013-0153-x
更新日期:2014-09-01 00:00:00
abstract::The technique of differential display reverse transcription-polymerase chain reaction (ddRT-PCR) has been used to produce unique profiles of up-regulated and down-regulated gene expression in the liver of male Wistar rats following short term exposure to the non-genotoxic hepatocarcinogens, phenobarbital and WY-14,643...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03190966
更新日期:1997-10-01 00:00:00
abstract:BACKGROUND:Aldehyde oxidase (AOX) is an important molybdenum-containing enzyme with high similarity with xanthine oxidase (XO). AOX involved in the metabolism of a large array of aldehydes and N-heterocyclic compounds and its activity is highly substrate-dependent. OBJECTIVES:The aim of this work was to study the effe...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s13318-018-0514-6
更新日期:2019-04-01 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 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::We have investigated the in vitro metabolism of three small antimicrobial β(2,2)-amino acid derivatives (M (w) < 500) that are highly potent against methicillin resistant Staphylococcus aureus, and are among the first compounds designed from small cationic antimicrobial peptides with potential ...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s13318-012-0086-9
更新日期:2012-09-01 00:00:00
abstract::Bioavailability of lansoprazole, a new gastric proton pump inhibitor, was investigated in 12 healthy subjects. Each subject received in random order, lansoprazole (30 mg) alone or associated with standard meal or with antacids (aluminium and magnesium hydroxides) or one hour later than antacids. Lansoprazole and metab...
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:
更新日期:1991-01-01 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::The original version of this article unfortunately contained a mistake. ...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章,已发布勘误
doi:10.1007/s13318-020-00611-x
更新日期:2020-06-01 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::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::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::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::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 radioact...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03189631
更新日期:1982-10-01 00:00:00
abstract::The purpose of this study was to investigate the possibility of developing different levels of in vitro-in vivo correlation for immediate-release paracetamol tablets using in vitro dissolution data obtained under various experimental conditions. The influence of agitation intensity and pH value of the dissolution medi...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03189824
更新日期:1998-01-01 00:00:00
abstract::Pharmacokinetics of ketoprofen (KTP) enantiomers has been studied in patients with rheumatoid arthritis (RA) following administration of a single oral dose of 100 mg rac-KTP during multidrug therapy taking into consideration the genotype of RA patients Concentrations of (-)-R and (+)-S enantiomers of KTP in plasma, ur...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s13318-011-0041-1
更新日期:2011-09-01 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 study was to accelerate the dissolution of the sustained release dosage forms using both elevated temperature and high rpm rates. Teokap(®) SR 200 mg pellets were tested by in vitro sustained and accelerated dissolution studies using USP XXIII rotating paddle method. Sustained dissolution studies were c...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s13318-011-0049-6
更新日期:2011-12-01 00:00:00
abstract::The disposition of RS-tocainide in three healthy volunteers has been studied after oral administration of a pseudoracemic mixture containing S(+) [3H] tocainide as a radioactive tracer together with a therapeutic dose of the racemate. Analytical methods based on HPLC have been developed to measure S(+) and R(-) tocain...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03189644
更新日期:1984-07-01 00:00:00
abstract::A short review on some pharmacokinetic parameters (mean residence time, sojourn time, transit time) is given in relation to compartmental models and some examples and application are discussed. In particular the use of the sojourn time is suggested because this parameter can give useful informations when comparing the...
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 kinetics of five cisplatin analogs binding to human plasma fractions possessing a molecular weight greater than 50,000 daltons were studied. Each drug solution in plasma ultrafiltrate or phosphate buffer (pH = 7.4, mu = 0.154) was mixed with human plasma and filterable platinum concentrations were measured versus ...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03189700
更新日期:1985-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:In the present work, pharmacological and pharmacokinetic properties of the supramolecular complex of non-steroid anti-inflammatory drug ibuprofen (IBU) with natural polysaccharide arabinogalactan (AG) were studied. The main goals of such complexation were the increase of ibuprofen's bioavailab...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s13318-016-0357-y
更新日期:2017-06-01 00:00:00
abstract::The disposition of cloflumide (VUFB 15496), 2-chloro-7-fluoro-10 [4-(carbamoylethyl)piperazino]-10,11-dihydrodibenzo [b,f] thiepin methansulfonate, a new neuroleptic agent, following single oral and intravenous dose was studied in the rat using radiotracer techniques. [3H]Cloflumide was almost completely absorbed from...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03189883
更新日期:1987-04-01 00:00:00
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