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 and nine with moderate hepatic impairment (Child-Pugh class B) received one rotigotine transdermal patch (providing a dose of 2 mg/24 h) daily for 3 days with a 24-h patch-on period. Blood and urine samples were collected to evaluate pharmacokinetic parameters characterizing drug bioavailability and elimination. Primary variables included plasma and urine concentrations of unconjugated rotigotine (active parent compound) and total rotigotine (unconjugated rotigotine plus sulfate and glucuronide conjugates) under steady-state (SS) conditions. For unconjugated rotigotine, point estimates for the ratios of AUC(0-24)SS and C max,SS between the two groups (normal vs. impaired hepatic function) were near 1: AUC(0-24)SS, 0.90 (90 % CI 0.59, 1.38) and C max,SS, 0.94 (90 % CI 0.66, 1.35); t max,SS and t 1/2 were lower in subjects with hepatic impairment, while renal clearance was unaffected and overall clearance was higher. For total rotigotine, C max,SS was higher in subjects with hepatic impairment compared with those with normal hepatic function (P = 0.0239, ANOVA). A tendency to reduced non-renal clearance was observed in subjects with hepatic impairment, consistent with their higher plasma concentrations of total rotigotine. Thus, moderate hepatic impairment did not influence the pharmacokinetics of unconjugated rotigotine under steady-state conditions suggesting that dose adjustment will not be required for patients with mild or moderate hepatic insufficiency. In addition, the rotigotine patch was well tolerated in subjects with moderate hepatic impairment.
journal_name
Eur J Drug Metab Pharmacokinetjournal_title
European journal of drug metabolism and pharmacokineticsauthors
Cawello W,Fichtner A,Boekens H,Braun Mdoi
10.1007/s13318-013-0153-xsubject
Has Abstractpub_date
2014-09-01 00:00:00pages
155-63issue
3eissn
0378-7966issn
2107-0180journal_volume
39pub_type
杂志文章,多中心研究abstract::Changes in liver perfusion may have a substantial influence on the pharmacokinetics of drugs with flow-controlled metabolism. This may have important implications for drug dosage in patients in an intensive care unit (ICU). The hepatic D-sorbitol plasma clearance has been suggested as a non-invasive test for evaluatin...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03190181
更新日期:1993-10-01 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::The metabolism of galanthamine hydrobromide (Nivalin) was investigated in rat and rabbit liver homogenates. Experiments were carried out varying several parameters of incubation: substrate (galanthamine hydrobromide, galanthamine, galanthaminone and epigalanthamine), cofactor enrichment (NADPH, NADP/G-6-P, NAD), pH (7...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03189858
更新日期:1987-01-01 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: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::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::Blood loss during cesarean section was calculated based on post-operative decrement of hemoglobin (Hb) and hematocrit (Hct) level. The model used for pregnant women was previously validated for non-pregnant women who underwent gynecological surgery. 1,068 pregnant women who underwent cesarean section and 517 women who...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s13318-011-0042-0
更新日期:2011-09-01 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::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::[14C]Haloperidol decanoate was hydrolysed by partially purified carboxylesterase but not in plasma, blood, lymph and lymphatic liquid. These fluids inhibited the enzyme-mediated hydrolysis of the ester. Within the same incubation period as above, the ester was found hydrolysed to various extents in cell cultures of is...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03189895
更新日期:1987-07-01 00:00:00
abstract::Urodynamic model was developed which, in conjunction with a compartmental pharmacokinetic model, was used for study of factors influencing drug concentrations in urine: urine flow rate, residual bladder urine, maximal bladder urine, stage of renal failure, and elimination kinetics of drugs. Norfloxacin (NOR) was used ...
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:BACKGROUND AND OBJECTIVES:Ketoprofen, a potent nonsteroidal anti-inflammatory drug, is clinically administered as a racemic mixture. One of the possible metabolism routes of ketoprofen is the inversion of the R- to S-enantiomer in the gastrointestinal tract. Ketoprofen, as a weak acid drug, might undergo recirculation ...
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/s13318-015-0313-2
更新日期:2016-12-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Acetaminophen (APAP, paracetamol) is currently the principal cause of acute liver failure in both the USA and the UK. However, relatively little is known about the influence of genes and race/ethnicity on the disposition of APAP and the extent to which genetic variation and ethnicity may predi...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s13318-016-0329-2
更新日期:2017-02-01 00:00:00
abstract::The effects of potassium ethylxanthogenate (PEX) and 2,3-Dimercaptopropane sulphonate sodium (Unithiol) on the pentobarbital (40 mg/kg, body weight i.v.) (PB) sleeping time, pharmacokinetics, and metabolism, were studied in comparative experiments on male albino mice. It was established that the pretreatment of animal...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03189539
更新日期:1982-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:LCZ696 (sacubitril/valsartan), a novel angiotensin receptor neprilysin inhibitor has been recently approved for the treatment of patients with heart failure (HF) and reduced ejection fraction. As several HF patients are likely to use statins as co-medications, the potential for a pharmacokineti...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 临床试验,杂志文章
doi:10.1007/s13318-016-0349-y
更新日期:2017-04-01 00:00:00
abstract::The binding of three digitalis glycosides, digitoxin, digoxin and gitoxin, to human serum albumin was studied in vitro by equilibrium dialysis. The results obtained showed that binding is a non saturable process and that probably the same binding mechanism is involved for each of the three drugs. Their binding sites s...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03189456
更新日期:1980-01-01 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 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::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 biotransformation of 1-(3-butoxy-2-carbamoyloxypropyl)-5-ethyl-5-phenyl-(1H,3H,5H)-pyrimidine-2,4,6-trione (febarbamate) has been investigated in man. Human volunteers received a single oral dose of 15 mg/kg febarbamate. Twenty two metabolites found in urine were separated and purified by means of an extraction wi...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03188760
更新日期:1983-07-01 00:00:00
abstract::Cytochrome P450 from rat brain mitochondrial and microsomal fractions was found to be inducible by 3-methylcholanthrene, both in quantity of enzyme and in activity towards 7-ethoxyresorufin, which is a model substrate for the cytochrome P450 isoform specifically induced by 3-methylcholanthrene. Conversely, a phenobarb...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03189910
更新日期:1987-10-01 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::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::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::The pharmacokinetics of chlordemethyldiazepam--a pharmacologically very active new 1,4-benzodiazepine derivative--in healthy subjects after administration of a single oral dose of 2 mg, was studied. Peak concentrations were reached in 1.2 +/- 0.2 hours. Plasma levels declined with a biphasic pattern, and the eliminati...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03189844
更新日期:1986-07-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:UPARANT has emerged as a novel therapeutic agent with the potential to treat ocular diseases as assessed by studies in animal models. Since limited information is available on the pharmacokinetics of UPARANT, the aim of this study is to evaluate its pharmacokinetics after single and multiple a...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s13318-020-00654-0
更新日期:2021-01-01 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::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::Pharmacokinetic gender-dependent differences in cytochrome P450-mediated drug metabolism, especially CYP3A4, and their clinical implications are increasingly apparent. CYP3A4 seems to be the most important CYP isoform in both bioactivation and N-dechloroethylation of the alkylating prodrug ifosfamide, but informations...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03190396
更新日期:2001-07-01 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