Abstract:
:The MDR modulator, OC144-093, is a potential candidate for use in cancer therapy and exhibits potent biological activity in vitro and in vivo when combined with anticancer agents such as paclitaxel. Its inhibitory interaction with P-glycoprotein (Pgp), the mdr1 gene product and a mechanistic participant in multidrug resistance, underlies its activity as a modulator of MDR. Having previously shown that OC144-093 is not a substrate for CYP3A we first examined the effects of OC144-093 on paclitaxel metabolism in vitro. Using human liver microsomes, we have demonstrated that OC144-093 inhibited the CYP3A mediated metabolism of paclitaxel at high concentrations only (Ki = 39.8 +/- 5.1 microM, n=3). Pharmacokinetic results also show that an oral dose of OC144-093, co-administered with paclitaxel caused negligible disturbance of the pharmacokinetic profile for paclitaxel when injected intravenously. In contrast, AUC values were elevated approximately 1.5-fold in all groups treated orally with paclitaxel and OC144-093. Cmax was enhanced approximately 2-fold in the co-dosed group. These characteristics are consistent with Pgp blockade in the gut enhancing oral bioavailability. Elimination properties of paclitaxel were affected only upon multiple dosing of OC 144-093. These results warrant the further clinical assessment of OC144-093 as an MDR reversing agent.
journal_name
Eur J Drug Metab Pharmacokinetjournal_title
European journal of drug metabolism and pharmacokineticsauthors
Guns ES,Denyssevych T,Dixon R,Bally MB,Mayer Ldoi
10.1007/BF03190426keywords:
subject
Has Abstractpub_date
2002-04-01 00:00:00pages
119-26issue
2eissn
0378-7966issn
2107-0180journal_volume
27pub_type
杂志文章abstract::We retrospectively analyzed amikacin pharmacokinetics in 19 critically ill patients who received amikacin intravenously. Fourteen subjects (577 serum amikacin concentrations, 167 urine measurements) were studied to obtain data for population modeling, while 5 patients (267 serum amikacin concentrations, 68 urine measu...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03190009
更新日期:1999-01-01 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
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journal_title:European journal of drug metabolism and pharmacokinetics
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doi:10.1007/BF03189692
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abstract::Using in vitro dissolution and in vivo absorption of different generics or batches for an appropriate drug and dosage form, a reference equation of form: ka = a+bkd+dkd2 can be proposed. In the case of availability of standardised in vitro-in vivo data for a specific drug, a Level A a correlation of this type containi...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03188930
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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...
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pub_type: 杂志文章
doi:10.1007/BF03189844
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journal_title:European journal of drug metabolism and pharmacokinetics
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doi:10.1007/s13318-018-0473-y
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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
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doi:10.1007/s13318-010-0011-z
更新日期:2010-09-01 00:00:00
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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
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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
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journal_title:European journal of drug metabolism and pharmacokinetics
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更新日期:2003-04-01 00:00:00
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doi:10.1007/s13318-020-00645-1
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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
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更新日期:2016-12-01 00:00:00
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journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03189696
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journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章,评审
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doi:10.1007/s13318-016-0329-2
更新日期:2017-02-01 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::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
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doi:10.1007/BF03191165
更新日期:2009-07-01 00:00:00
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journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03190109
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journal_title:European journal of drug metabolism and pharmacokinetics
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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
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journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 临床试验,杂志文章
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abstract::The influence of phenobarbital pretreatment on liver concentration of digitoxin and its metabolites was studied in guinea-pigs after i.p. administration of the cardiac glycoside. During the first hour an increase in liver uptake was observed in pretreated animals. The differences detected in the hepatic subcellular di...
journal_title:European journal of drug metabolism and pharmacokinetics
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doi:10.1007/BF03189562
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journal_title:European journal of drug metabolism and pharmacokinetics
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doi:10.1007/s13318-015-0311-4
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journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
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更新日期:1991-01-01 00:00:00
abstract::The metabolism of (-)-(S)-nicotine has been investigated following intratracheal administration to the recirculating perfused rabbit lung model. The metabolic products present in the perfusate were identified by co-chromatography (HPLC and GC) with authentic standards and quantified by HPLC. After the 180 min perfusio...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03190976
更新日期:1997-10-01 00:00:00
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journal_title:European journal of drug metabolism and pharmacokinetics
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doi:10.1007/BF03189889
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journal_title:European journal of drug metabolism and pharmacokinetics
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abstract::Parenteral phenytoin solution (Dilantin) was given rectally three times a day for three days to two beagle dogs. This was well tolerated, with no evidence of mucosal irritation noted either on endoscopic nor on rectal mucosal biopsy. When given in this manner, phenytoin is absorbed to a limited degree in canines. Pare...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
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