Pharmacy and Pharmacology Communications最新文献

{"title":"HPLC‐NMR Spectroscopy","authors":"I. Wilson","doi":"10.1002/9780470034590.EMRSTM1193","DOIUrl":"https://doi.org/10.1002/9780470034590.EMRSTM1193","url":null,"abstract":"The linking of NMR spectroscopy on-line with a separation technique, such as high performance liquid chromatography (HPLC or LC), provides many advantages for the structural characterization of unknowns present in mixtures. In particular, the use of this on-line technology can remove the need for the isolation of the analyte in a pure form, thus improving both speed and efficiency. Technical advances such as the implementation of capillary techniques, cryoflow probes, and on-line sample concentration via solid phase extraction have all contributed to increasing the sensitivity of LC-NMR, thereby making the technique increasingly useful in a range of application areas including pharmaceutical and environmental analysis, natural products research, and studies on drug and xenobiotic metabolism. The combination with on-line mass spectrometry (MS) to provide LC-NMR-MS systems enables even more information to be recovered from samples. Here, the methods employed in LC-NMR, and LC-NMR-MS, for the analysis of chromatographic eluents are described and illustrated with representative applications. \u0000 \u0000 \u0000Keywords: \u0000 \u0000liquid chromatography; \u0000hyphenation; \u0000NMR spectroscopy; \u0000drug metabolites; \u0000natural products","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2011-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86061189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extraction of Peptidase Substrates by the Isolated Perfused Rat Lung","authors":"B. Forbes, Clive G. Wilson, M. Gumbleton","doi":"10.1111/J.2042-7158.1995.TB00381.X","DOIUrl":"https://doi.org/10.1111/J.2042-7158.1995.TB00381.X","url":null,"abstract":"Peptidases in the lung are well placed to have an important role in regulating levels of circulating endogenous and therapeutic peptides. They also present a first-pass metabolic barrier for peptides delivered to the lung for systemic absorption. The activities of five peptidases were surveyed in the pulmonary circulation of the asanguinous isolated perfused rat lung (IPRL) using synthetic substrates and selective inhibitors. \u0000 \u0000 \u0000 \u0000Extraction ratios (ER) were calculated for the substrates of: aminopeptidase N (AMN), ER 0·37 ± 0·04; dipeptidyl peptidase IV (DPP), ER 0·69 ± 0·05; and angiotensin-converting enzyme (ACE), ER 0·40 ± 0·02. These activities were inhibited (> 95%) by the selective inhibitors bestatin, diprotin A, and captopril, respectively. Substrates for neutral endopeptidase 24.11 (NEP) and carboxypeptidase M (CPM) were minimally degraded with ER of 0·02 and 0·00, respectively. \u0000 \u0000 \u0000 \u0000The low activity of NEP, a major membrane bound endopeptidase, indicates that the lungs may not contribute greatly to degradation of either systemic NEP substrates, or exopeptidase-resistant peptides absorbed from the peripheral lung. In contrast peptides susceptible to the exopeptidases AMN, DPP, and ACE, will be substantially degraded during passage through the lung. The absence of CPM activity in the pulmonary circulation of the asanguinous IPRL implies that basic carboxypeptidase activity in blood perfused lungs reported in the literature is more likely to be the result of plasma carboxypeptidase N activity.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2011-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81726357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Liposomes on Permeation of Diclofenac Through Cadaver Skin: In‐vivo Evaluation Using Animal Models","authors":"R. K. Bhardwaj, T. Velpandian, K. Kamal, S. Gupta","doi":"10.1211/146080800128735566","DOIUrl":"https://doi.org/10.1211/146080800128735566","url":null,"abstract":"Liposomes interact with the stratum corneum and may be responsible for enhanced transdermal drug penetration. This study was carried out to compare the effect of liposomes on the permeation of diclofenac sodium with the conventionally available non-liposomal diclofenac gel. \u0000 \u0000Preliminary in-vitro studies using fluorescein sodium as a marker showed 1.5- and 1.35- fold increased flux for small unilamellar vesicle and multilamillar vesicle liposome formulations, respectively, compared with non-liposomal fluorescein sodium. This was followed by diclofenac formulations, Lipogel-a (1% w/w diclofenac sodium), Lipogel-b (1.16% w/w diclofenac diethylammonium equiv. 1% w/w diclofenac sodium) and commercially available diclofenac gel. The Lipogel-a and Lipogel-b showed 2- and 1.5-times greater flux compared with conventional non-liposomal diclofenac gel. The pharmaco-kinetic profile in mice was studied as an experimental animal model and the drug concentration in blood was measured at various time points. Lipogel-a, Lipogel-b and conventional diclofenac gel were also compared for their anti-inflammatory activity using carrageenan and Freund's adjuvant models of inflammation. The significant pharmacokinetic profile and enhanced efficacy in pharmacodynamic parameters suggest that liposomes are responsible for enhanced drug penetration. \u0000 \u0000Liposomes enhance drug penetration across the epidermis and thus could be used as alternative carriers to organic and inorganic penetration enhancers.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72660184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Morphine Withdrawal‐induced Diarrhoea and Acetic Acid‐induced Abdominal Constriction: Animal Models for the Evaluation of 5‐HT3 Ligands in the Treatment of Irritable Bowel Syndrome","authors":"A. Veeranjaneyulu, N. Sridhar, R. J. Babu, C. Gupta, R. Malavika, S. Shobana","doi":"10.1211/146080800128735610","DOIUrl":"https://doi.org/10.1211/146080800128735610","url":null,"abstract":"The aim of the study was to evaluate the role of 5-HT3 receptor ligands in animal models of gastric hypermotility and visceral hyperalgesia, symptoms associated with irritable bowel syndrome. \u0000 \u0000 \u0000 \u0000The abrupt termination of sub-chronic morphine (in doses of 35, 70, 140 mg kg−1, i.p.) for four days by naloxone (43 mg kg−1 i.p., 3 h after the last morphine injection) results in withdrawal symptoms, of which diarrhoea and jumping behaviour are common in mice. The gastric hypermotility induced by morphine withdrawal is used as an animal model to evaluate 5-HT3 ligands. Acetic acid-induced abdominal constriction in mice serves as a model for visceral hyperalgesia. m-Chlorophenylbiguanide (mCPBG; 2 and 5 mg kg−1, i.p.) and ondansetron (3 and 6 mg kg−1, i.p.), 5-HT3 agonist and antagonist respectively, were used for the study. Ondansetron exhibited a dose-dependent inhibition of diarrhoea and significantly decreased the number of jumps. It also attenuated the abdominal constriction response induced by acetic acid in mice in a dose-dependent manner. mCPBG did not significantly alter diarrhoea or acetic acid-induced abdominal constriction. However mCPBG (5 mg kg−1, i.p) caused a significant increase in number of jumps. \u0000 \u0000 \u0000 \u0000The results suggest that 5-HT3 receptor modulators can be used for the treatment of GI dysmotility and associated nociception, and the above models can be used to evaluate 5-HT3 ligands, especially antagonists, in treatment of irritable bowel syndrome.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82227116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of Hyperthyroidism by Rauwolfia serpentina Root Extract in Mice","authors":"S. Panda, A. Kar","doi":"10.1211/146080800128735629","DOIUrl":"https://doi.org/10.1211/146080800128735629","url":null,"abstract":"The aim of this study was to determine the role of Rauwolfia serpentina root extract in the regulation of hyperthyroidism in mice. \u0000 \u0000 \u0000 \u0000In L-thyroxine (50 μg/100 g for 30 days)-treated mice, an increase in serum concentrations of both thyroid hormones (thyroxine and triiodothyronine) and in hepatic glucose-6-phosphatase activity was observed. Daily administration of the plant extract (2.5 mg kg−1) either alone or with thyroxine for 30 days decreased concentrations of both thyroid hormones, indicating the possible regulation of hyperthyroidism by the plant extract. The plant extract also decreased hepatic lipid peroxidation and increased super-oxide dismutase and catalase activity in hyperthyroid mice without hepatotoxic effects. \u0000 \u0000 \u0000 \u0000R. serpentina root extract might be a potentially effective treatment for hyperthyroidism.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75204260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ranitidine Increases Bioavailability of Acetaminophen by Inhibiting First‐Pass Glucuronidation in Man","authors":"H. Itoh, T. Nagano, Tetsuji Hayashi, M. Takeyama","doi":"10.1211/146080800128735584","DOIUrl":"https://doi.org/10.1211/146080800128735584","url":null,"abstract":"The effect of the histamine H2 receptor antagonist, ranitidine, on plasma concentrations of acetaminophen was investigated with respect to hepatic metabolism, in five volunteers. Acetaminophen (1000 mg) together with ranitidine (300 mg), placebo or at 1 h after ranitidine (300 mg) was orally administered to five healthy male volunteers. Venous blood samples were taken before and after drug administration. Plasma acetaminophen and acetaminophen conjugates (glucuronide and sulphate) were determined by HPLC. The pharmacokinetic parameters were calculated from the plasma acetaminophen concentration-time curves from each volunteer. The area under the plasma acetaminophen concentration-time curve from 0 to 3 h (AUC0–3) significantly (P < 0.01) increased from 13.03 ± 0.84 μg h mL−1 (placebo coadministration) to 21.30 ± 0.60 μg h mL−1 (ranitidine coadministration). The peak plasma acetaminophen concentration significantly (P < 0.01) increased from 18.30 ± 2.26 μg mL−1 (placebo coadministration) to 34.14 ± 1.07 μg mL−1 (ranitidine coadministration) 30 min after administration. Plasma acetaminophen concentrations with ranitidine were significantly increased at 15 to 120 min compared with placebo. Plasma acetaminophen glucuronide conjugate concentrations with ranitidine were significantly decreased at 15 to 45 min compared with placebo, whereas plasma acetaminophen sulphate conjugate concentrations were not significantly altered. Plasma acetaminophen and acetaminophen conjugate concentrations were not significantly different between placebo-coadministration and in the case where acetaminophen was orally administered 1 h after ranitidine. \u0000 \u0000 \u0000 \u0000Coadministration of acetaminophen and ranitidine reduced plasma acetaminophen glucuronide concentrations and significantly increased plasma acetaminophen concentrations. The effects of ranitidine are as a result of the prevention of first-pass hepatic metabolism, by prevention of acetaminophen glucuronyltransferase. Thus care must be taken when acetaminophen and ranitidine are coadministered.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90699757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non‐Peptidic, Non‐Prenylic Bisubstrate Farnesyltransferase Inhibitors. Effect of a Carboxyl Group at the Central Group on Farnesyltransferase Inhibitory Activity","authors":"M. Schlitzer, I. Sattler","doi":"10.1211/146080800128735601","DOIUrl":"https://doi.org/10.1211/146080800128735601","url":null,"abstract":"We recently described non-peptidic, non-prenylic bisubstrate analogues as novel farnesyl-transferase inhibitors comprising three modules-a farnesyl-mimetic, a linker and an AAX-peptidomimetic substructure. In this study, we replaced the originally used β-alanyl linker with aminomalonic, aspartic and glutamic acid, respectively, to introduce a second functional group capable of complexing the essential zinc ion, located in the active site of farnesyltransferase. \u0000 \u0000 \u0000 \u0000Apart from aminomalonic acid, all moieties showed reduced inhibitory activity. Interestingly, the benzyl esters of the aspartic and glutamic acid derivatives were more active than the free acids. \u0000 \u0000 \u0000 \u0000The results provide further evidence for an additional lipophilic binding cleft in the active site of farnesyltransferase.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89503708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Degradation of Rifampicin, Isoniazid and Pyrazinamide from Prepared Mixtures and Marketed Single and Combination Products Under Acid Conditions","authors":"Saranjit Singh, T. Mariappan, N. Sharda, Baljinder Singh","doi":"10.1211/146080800128735575","DOIUrl":"https://doi.org/10.1211/146080800128735575","url":null,"abstract":"This study was carried out to determine the extent of degradation of rifampicin, isoniazid and pyrazinamide from prepared mixtures and marketed preparations containing single, two, three and four drugs, under stomach conditions. \u0000 \u0000Degradation studies were carried out in 0.1 M HC1 at 37°C for 50 min. A comparative study in simulated gastric fluid was also done. Under both conditions, rifampicin was decomposed by 17.8–24.4%, isoniazid to a lesser extent (3.2–4.7%), and pyrazinamide was stable. The decomposition of rifampicin was influenced by the presence of isoniazid but not by pyrazinamide or ethambutol. Compared with pure drugs and mixtures, wide variations in the decomposition of rifampicin (7.5–33.3%) and isoniazid (1.4–5.3%) were found in the marketed fixed-dose combinations, indicating the influence of formulation and storage conditions. \u0000 \u0000The results suggest that the poor bioavailability of rifampicin might be in part due to the decomposition of the drug in the stomach. The recent WHO protocol suggests the comparison of the test fixed-dose combination preparations against a combination of separate formulations of two, three or four drugs. However, it may be more meaningful to carry out bioequivalence studies on fixed-dose combination formulations by comparing the test fixed-dose combination preparations with the standard formulations of individual drugs.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82264863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simultaneous Determination of Aciclovir and Ganciclovir in Plasma by HPLC and Pharmacokinetic Interactions","authors":"N. Shibata, A. Kitamura, Y. Yoshikawa, T. Inoue, T. Bamba, K. Takada","doi":"10.1211/146080800128735593","DOIUrl":"https://doi.org/10.1211/146080800128735593","url":null,"abstract":"In this study, we developed a simultaneous determination of the antiviral drugs, aciclovir and ganciclovir, in patient and rat plasma. We also confirmed any potent pharmacokinetic interactions between these two drugs. \u0000 \u0000 \u0000 \u0000Precipitation and extraction of aciclovir, ganciclovir, and an internal standard (5-fluoro-2′-deoxyuridine) was achieved by adding 12.5% trichloroacetic acid solution. Separation of the three compounds was performed by a reversed-phase liquid chromatography, and the peaks of compounds were detected spectrophotometerically at 280 nm. The working curves by a least-squares linear regression over the range 0.1–10 μg ML−1 passed through the origin with a correlation coefficient of 0.999 or better, and the results of within-day and between-day precisions were adequate for clinical use. The therapeutic windows of aciclovir and ganciclovir (from the lower to the upper quartile), estimated by measuring clinical plasma samples, were from 0.40 to 0.63 μg mL−1 and from 0.29 to 0.51 μg mL−1, respectively. The trough plasma concentrations of ganciclovir from patients with bone marrow transplants increased significantly when aciclovir was co-administered, and the area under the concentration-time curve of ganciclovir and aciclovir after intravenous coadministration of these drugs in rats showed approximately 2.4- and 1.5-fold increase, respectively, suggesting the existence of some drug interaction between aciclovir and ganciclovir. \u0000 \u0000 \u0000 \u0000The HPLC assay method developed here could be used for the rapid pharmacokinetic study in rats and the clinical monitoring of the concentrations of aciclovir and ganciclovir in human plasma with a minimum sample volume of 100 μL.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80583582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preparation and Evaluation of Liposomal Flucinolone Acetonide Gel for Intradermal Delivery","authors":"G. Rao, R. Murthy","doi":"10.1211/146080800128735557","DOIUrl":"https://doi.org/10.1211/146080800128735557","url":null,"abstract":"Hydroxypropyl methylcellulose (HPMC) K4M gels containing free flucinolone acetonide, liposomal-encapsulated flucinolone acetonide and physical mixture of the drug and lipids were prepared and evaluated in in-vitro drug release studies using rat skin to determine diffusion parameters. \u0000 \u0000Data were analysed to calculate the quantity of the drug remaining in the skin (Qm) and in the blood (Csf) and the ratio of Qm to Csf. The in-vivo skin blanching assay performed with these formulations in human volunteers showed low blanching scores for liposomal gel formulations indicating low absorption of the liposomal-encapsulated drug into the blood stream and leading to the accumulation of the drug in the skin. This result is in agreement with the high Qm/Csf ratios obtained in the in-vitro experiments. \u0000 \u0000Of all the formulations, gels containing liposomal-encapsulated flucinolone acetonide, prepared with drug, phosphatidyl choline and cholesterol in the ratio of 4:8:1, had the highest Qm/Csf ratio and minimum blanching score. The results indicate the potential of topical preparations containing liposomal-encapsulated drugs for selective accumulation of the drug in the skin.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75327684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}