Novel Hybrid Peptide Cecropin A (1-8)-LL37 (17-30) with Potential Antibacterial Activity.

Hybridizing different antimicrobial peptides (AMPs) is a particularly successful approach to obtain novel AMPs with increased antimicrobial activity but minimized cytotoxicity. The hybrid peptide cecropin A (1-8)-LL37 (17-30) (C-L) combining the hydrophobic N-terminal fragment of cecropin A (C) with the core antimicrobial fragment of LL37 (L) was designed and synthesized. C-L showed higher antibacterial activity against all indicator strains than C and L, and no hemolytic activity to sheep erythrocytes was observed. C-L kills bacterial cells and causes disruption of surface structure, as determined by scanning electron microscopy. Synergistic effects were observed in the combination of C-L with several antibiotics (chloramphenicol, thiamphenicol, or neomycin sulfate) against Escherichia coli and Staphylococcus aureus.

[Impact of cytochrome P450 CYP2C9 variant allele CYP2C9 * 3 on the pharmacokinetics of glibenclamide and lornoxicam in Chinese subjects].

AIM: To investigate the impact of CYP2C9 * 3 on the pharmacokinetics of glibenclamide and lornoxicam. METHODS: CYP2C9 * 3 was measured in 83 non-related Chinese subjects by PCR-RFLP. The pharmacokinetics of lornoxicam and glibenclamide were investigated in 18 subjects (7 with CYP2C9 * 1/* 3 genotype and 11 with * 1/* 1 genotype). Glibenclamide and lornoxicam in plasma were determined by the sensitive liquid chromatography-tandem mass spectrometry, separately. RESULTS: After a single oral dose of 2.5 mg glibenclamide, C(max) was (70.0 +/- 11.5) microg x L(-1) in CYP2C9 * 1/ * 3 subjects and (51.9 +/- 12.3) microg x L(-1) in * 1/ *1 subjects. AUC(0-infinity) were (435 +/- 47) vs (287 +/- 95) microg x h x L(-1) (in * 1/ * 3 vs * 1/ *1 subjects), and CL/F were (96 +/- 9.3) vs (160 +/- 51) mL x min(-1), respectively. Statistic analysis results indicated that glibenclamide AUC(0-infinity) was significantly higher (1.5-fold) and subsequently CL/F was significantly lower (40%) in CYP2C9 * 1/ * 3 subjects than those in * 1/ * 1 subjects (P < 0.01). After a single oral dose of 8 mg lornoxicam, C(max) was (1.54 +/- 0.24) mg x L(-1) in CYP2C9 * 1/ * 3 subjects and (1.19 +/- 0.37) mg x L(-1) in * 1/ * 1 subjects. AUC(o-infinity were (14.9 +/- 2.2) vs (6.92 +/- 1.48) mg x h x L(-1) (in * 1/ *3 vs * 1/ * 1 subjects), and CL/F were (9.1 +/- 1.2) vs (20.1 +/- 4.6) mL x min(-1), respectively. Statistic analysis results indicated that lornoxicam AUC(0-infinity) was significantly higher (2. 2-fold) and subsequently CL/F was significantly lower (55% ) in CYP2C9 * 1/ * 3 subjects than those in * 1/ * 1 subjects (P < 0.001). CONCLUSION: CYP2C9 * 3 greatly affects both the pharmacokinetic profiles of glibenclamide and lornoxicam. The elimination of these drugs significantly decreased in subjects with CYP2C9 * 1/ * 3 genotype, especially lornoxicam.