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MARINA GOBBO LAURA BIONDI FERNANDO FILIRA TOM PIEK RANIERO ROCCHI 《Chemical biology & drug design》1995,45(5):459-465
Syntheses are described of the endo-Lys8a-vespulakinin 1 and of cyclo-Thr6- and cyclo-Nε-Lys-bradykinin. The linear peptides covering the entire sequences of endo-Lys8a-VSK-1 and Thr6-BK, and the decapeptide containing all residues constituting Lys-BK, with a Arg-Lys peptide bond involving the ε-amino function of lysine, were prepared by the solid-phase procedure based on Fmoc chemistry. Cyclization was carried out by the diphenylphosphorazide method. The amino-terminal octapeptide sequence of vespulakinin 1, Fmoc-Thr(tBu)-Ala-Thr(tBu)-Thr(tBu)-Arg(Pmc)-Arg(Pmc)-Arg(Pmc)-Gly-OH, and its Nα-Boc-[(Gal β)Thr3, (Gal β)Thr4]-analogue, were used to prepare Nα-(1–8 VSK 1)-cyclo-Nε-kallidin and Nα-[(Gal β)Thr3, (Gal β)Thr4, 1–8 VSK 1]-cyclo-Nε-kallidin. Peptides and glycopeptides were characterized by amino-acid analysis, optical rotation, analytical HPLC and FAB-MS. Consistent with previous findings, preliminary pharmacological experiments on smooth muscle preparations showed that the cyclic, or partially cyclic, analogues were significatively less potent than the linear ones. © Munksgaard 1995. 相似文献
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TOM B. VREE MAGDALENA VAN DEN BIGGELAAR-MARTEA CORRIEN P.W.G.M. VERWEY-VAN WISSEN 《The Journal of pharmacy and pharmacology》1995,47(11):964-969
The pharmacokinetics of 80 mg frusemide given orally were investigated in normal subjects using a direct HPLC method for parent drug and its acyl glucuronide conjugate. Two half-lives could be distinguished in the plasma elimination of both frusemide and its conjugate, with values of 1.25 ± 0.75 and 30.4 ± 11.5 h for frusemide and 1.31 ± 0.60 and 33.2 ± 28.0 h for the conjugate. The renal excretion rate-time profile showed two phases; the rapid elimination phase lasted from 0–15 h and the second and slow phase, from 15–96 h. During the first 15 h, 33.3 ± 4.8% of the dosed frusemide was excreted; in the remaining period 15–96 h, 4.6 ± 1.5% was excreted. In the same two periods the excretion of the glucuronide was 13.4 ± 4.7 and 1.9 ± 1.1%, respectively. The mean renal clearance of frusemide was 90.2 ± 16.9 mL min?1 during the first period and 91.5 ± 29.3 mL min?1 in the remaining period, during which the stimulation of urine production was absent. The renal clearance of the acyl glucuronide was 702 ± 221 mL min?1 in the first period, but only 109 ± 51.0 mL min?1 in the second period. The stimulated urine production in the first 6 h after administration amounted to 2260 ± 755 mL (measured urine production minus baseline value of 1 mL min?1 (360 mL). During the second or rebound period (6–96 h after drug administration), the quantity of urine was 990 ± 294 mL lower than what would have been expected from the baseline production of 5400 mL. This reduced production (0.82 mL min?1) is equivalent to an 18% reduction in the average urine flow rate of 1 mL min?1. 相似文献
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C. J. McCARTHY R. COLLINS S. BEATTIE H. HAMILTON C. O'MORAIN 《Alimentary pharmacology & therapeutics》1993,7(4):463-466
Omeprazole heals most duodenal ulcers after 4 weeks of treatment but relapse is common. Eradication of Helicobacter pylori is associated with reduced rate of ulcer relapse. This study investigates the effect of omeprazole with antibiotics in H. pylori-associated duodenal ulceration. Forty-three patients with endoscopically proven duodenal ulcer and H. pylori entered this study. Treatment consisted of 20 mg omeprazole daily (four weeks) and seven days (first week) treatment with 400 mg metronidazole t.d.s. and 500 mg tetracycline t.d.s. Four weeks after completing the treatment, 81 % (35143) had a healed duodenal ulcer, and 58% (25/43) had H. pylori eradication. In those who healed, at one year 21 remained H. pylori-negative, 12 had persistent H. pylori infection and 2 had re-infection. The ulcer relapse rate at one year was 26%: of the 9 who relapsed, 6 had persistent infection, 2 were re-infected, and only 1 was H. pylori-negative. This combination therapy of antibiotics with omeprazole successfully eradicates Helicobacter pylori and has a lower ulcer replase than omeprazole alone. 相似文献