Abstract:
:The main objective of this study was to investigate the release and pharmacokinetic profiles of ketoprofen (KP) from developed thermosensitive and mucoadhesive liquid suppositories. Thermosensitive liquid suppositories were prepared using KP, poloxamer 407 (P 407), poloxamer 188 (P 188) and various amounts of different mucoadhesive polymers. In vitro release studies was monitored by the USP XXVI paddle method. The results thus obtained were evaluated kinetically and mechanism of release was analyzed. Identification of poloxamer gel localization in vivo was conducted using white male rabbits by adding 1 % methylene blue. For in vivo studies, twenty-four white male rabbits were randomly divided into three groups. The rabbits in each group were administered with liquid suppository F1 [P407/P188/KP (4/20/2.5 %)], F5 [P407/P188/KP/C (4/20/2.5/0.8 %)] or conventional suppository (F-C) into the rectum. The plasma concentration of KP was analyzed by high performance liquid chromatography (HPLC). C max, AUC, MRT and T max were evaluated. The release of KP was variously affected by the mucoadhesive polymers. In vitro release studies showed that Carbopol 934 P(C) has significant effect on release rate among the mucoadhesive polymers. When the formulations were evaluated kinetically, different kinetic models were obtained. Formulation F6 [P407/P188/KP/C (4/20/2.5/1.6 %)] which contains the highest C concentration and very high viscosity, shows a significantly better fit with Higuchi kinetic model. n value of this formulation was also found approximately 0.5. n exponent results of the other formulations showed that KP might be released from the suppositories by non-Fickian diffusion. Identification of poloxamer gel localization in vivo showed that the suppositories remain in the rectum without leakage after administration. With regard to the results of in vivo studies, the AUC6→14 values of KP in liquid suppository containing C are significantly higher than those in liquid suppository without C. MRT0→24 and MRT0→∞ values of liquid suppository containing C are significantly higher than those in liquid suppository without C and conventional suppository. Conventional suppository and liquid suppository without C significantly gave faster time to reach the maximum plasma concentrations of KP. With regard to the in vitro and in vivo experiments, liquid suppository formulation F5 might be a promising formulation for the development of an effective rectal dosage form.
journal_name
Eur J Drug Metab Pharmacokinetjournal_title
European journal of drug metabolism and pharmacokineticsauthors
Ozgüney I,Kardhiqi A,Yıldız G,Ertan Gdoi
10.1007/s13318-013-0157-6subject
Has Abstractpub_date
2014-12-01 00:00:00pages
283-91issue
4eissn
0378-7966issn
2107-0180journal_volume
39pub_type
杂志文章abstract::The pharmacokinetics, biotransformation, protein binding and tissue distribution of mitonafide and pinafide were studied after single i.v. and oral administration of each drug (20 mg/Kg) in female rats. In pregnant rats a study of cross placental-barrier after i.v. administration of the two drugs was also performed. T...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03189110
更新日期:1986-10-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Clopidogrel is an antiplatelet and antithrombotic prodrug. It has poor oral bioavailability due to poor dissolution and possible premature degradation in the intestine. Accordingly, the objective of this study was to enhance clopidogrel dissolution rate and to reduce its premature degradation ...
journal_title:European journal of drug metabolism and pharmacokinetics
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更新日期:2016-12-01 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...
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更新日期:1995-07-01 00:00:00
abstract::The effects of aluminium, manganese, ferrous and ferric iron, cobalt, nickel, copper, zinc, cadmium, barium, mercury and lead ions on the rat hepatic UDPglucuronosyltransferase activity with regard to 4-methylumbelliferone, 4-nitrophenol, bilirubin, and 2-aminophenol were investigated in vitro. Conjugation of bilirubi...
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更新日期:1980-01-01 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...
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pub_type: 杂志文章,评审
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更新日期:2006-07-01 00:00:00
abstract::Danirixin (GSK1325756) is a small, high-affinity, selective and reversible CXCR2 antagonist in development for treatment of chronic obstructive pulmonary disease. The objective of the study was to evaluate the relative bioavailability, including the inter-subject variability, of a conventional immediate-release (IR) f...
journal_title:European journal of drug metabolism and pharmacokinetics
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更新日期:2014-09-01 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/BF03190121
更新日期:1990-01-01 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
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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:1988-04-01 00:00:00
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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:1984-01-01 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
更新日期:1989-10-01 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
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更新日期:1995-04-01 00:00:00
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pub_type: 杂志文章
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更新日期:1995-10-01 00:00:00
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journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03189562
更新日期:1982-01-01 00:00:00
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pub_type: 杂志文章
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journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
doi:10.1007/BF03190163
更新日期:1992-10-01 00:00:00
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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
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更新日期:2018-04-01 00:00:00
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更新日期:2018-02-01 00:00:00
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pub_type: 临床试验,杂志文章
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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::A major biotransformation pathway for many NSAIDs from the group of optically active 2-arylpropionic acids is the conjugation with D-glucuronic acid, forming diastereomers. These conjugates of the S-(+)-and the R-(-)-enantiomers can be separated directly, e.g., by ion-pair chromatography on a C18-column using a mixtur...
journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
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更新日期:1987-10-01 00:00:00
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journal_title:European journal of drug metabolism and pharmacokinetics
pub_type: 杂志文章
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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
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更新日期:1997-01-01 00:00:00
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pub_type: 杂志文章
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更新日期:2013-06-01 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...
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更新日期:2020-12-01 00:00:00