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@#To further explore an efficient strategy for the construction of antitumor fluoroquinolone molecules from antibacterial fluoroquinolone drugs, twelve new title compounds, 1-ethyl-6-fluoro-7-(4-methyl-piperazin-1-yl)-3-(3-substituted-rhodanin-5-ylidene)methyl-quinolon-4(1H)-ones(6a-6l), was designed and synthesized with α, β-unsaturated ketone scaffold and a rhodanine ring as an isostere and fused modified group, respectively, from pefloxacin(1), and their structures were characterized by elemental analysis and spectral data. The in vitro anti-cell proliferative activity of the title compounds against the tested A549, Hep-3B and HL60 cancer cells exhibited more significant potency than parent 1. In particular, halogenated phenyl title compounds(6d, 6e, 6f)displayed a comparable activity to comparison doxorubicin against A549 cells and low cytotoxicity against normal Vero cells. Thus, a methylene rhodanine scaffold as a bioisostere of the C-3 carboxylic acid group have shown to be beneficial to improving the antitumor activity.
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Objective To evaluate combination therapy effects of ornidazole and pefloxacin on chronic periodontitis.Methods 200 cases of chronic periodontitis were chosen from the Stomatological Hospital of Hangzhou as study subjects.100 cases in observation group were treated with ornidazole and pefloxacin combination treatment, while another 100 cases in control group were treated with ornidazole.The treatments lasted 7 days.The effects and inflammation -related perimeters (including hs -CRP,IL -4,IL -6,IFN -γ)in patients'serum were measured. Results Probing depth,attachment loss and inflammation -related perimeters of the observation group were improved significantly,and even were much better than the control group (probing depth:t =2.113,P <0.05;attachment loss:t =1.894,P <0.05,hypersensitive C -reactive protein:t =2.001,P <0.05;IL -6:t =1.953,P <0.05;interferon -γ:t =1.976,P <0.05).And the total effective rate of the observation group was also better than that of the control group (χ2 =24.335,P <0.01).Conclusion Combination treatment of ornidazole and pefloxacin is more effective than single treatment of ornidazole,which is worthy of widely promoted in clinical.
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Objective:To develop a method of near infrared reflectance spectroscopy ( NIRS) for the rapid determination of peflox-acin mesylate for injection .Methods:The quantitative models were established by the collection of NIR spectra of pefloxacin mesylate for injection.The spectra were pretreated with the methods of vector normalization , and the spectral ranges of 9 176.2-8 169.5 cm-1 , 6 051.9-5 716.3 cm-1 and 4 509-3 999.9 cm-1 were chosen.The partial least square (PLS) was used as the regression method .Re-sults:The prediction model was established by the internal cross validation ,and the concentration range was 7.55%-77.69%.The root mean square error of cross validation (RMSECV) was 1.61%, and the correlation coefficient was 0.992 4.Conclusion: The method of near infrared reflectance spectroscopy can be used for the rapid quantitative analysis of pefloxacin mesylate for injection .
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@#To improve the antitumor activity of fluoroquinolones for a promising development of druggability, twelve novel fluoroquinolone C-3 s-triazole sulfide-one thiosemicarbazone derivatives(6a-6l)were designed and synthesized with a functionalized sulfide-one thiosemicarbazone as a modified side-chain for the C-3 bioisteric s-triazole ring of pefloxacin(1). The structures were characterized by elemental analysis and spectral data。The in vitro antitumor activity of novel compounds against SMMC-7721, L1210 and HL60 cell lines was evaluated. The preliminary pharmacological results demonstrated that the title compounds exhibited more significantly antiproliferative activity than either the parent 1 or the corresponding sulfide-one intermediates(5a-5l). In particular, compounds bearing a hydroxyl group or a fluorine atom attached to benzene ring were comparable to the control doxorubicin with an IC50 value of micro-molar concentration, respectively. It suggests that an azole ring modified with functional side-chain instead of the C-3 carboxylic group is favorable to the improve ment of antitumor activity.
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Objective: To evaluate the effect of Manix?, the commonly used polyherbal formulation on pefloxacin pharmacokinetic parameters.Methods:from hospitalized patients.Results:Microbiological assay was employed using clinical isolate of Escherichia coli samples Manix? altered the bioavailability parameters of pefloxacin as thus, maximal concentration (Cmax) of pefloxacin (0.91±0.31) μg/mL occurred at time to reach maximal concentration (tmax) 4.0 h while in the group that received Manix? alongside pefloxacin Cmax was (0.22±0.08) μg/mL at tmax 1.0 h respectively. The area under curve of pefloxacin alone was (7.83±5.14) μg/h/mL while with Manix? was (2.60±0.08) μg/h/mL. There was a significant difference between Cmax, tmax and area under curve between pefloxacin alone and pefloxacin after Manix? pre-treatment (P<0.05).Conclusions:The concurrent use of Manix? and pefloxacin has been found to compromise the therapeutic effectiveness of pefloxacin which could lead to poor clinical outcomes in patients.
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<p><b>OBJECTIVE</b>To evaluate the effect of Manix®, the commonly used polyherbal formulation on pefloxacin pharmacokinetic parameters.</p><p><b>METHODS</b>Microbiological assay was employed using clinical isolate of Escherichia coli samples from hospitalized patients.</p><p><b>RESULTS</b>Manix® altered the bioavailability parameters of pefloxacin as thus, maximal concentration (Cmax) of pefloxacin (0.91±0.31) µg/mL occurred at time to reach maximal concentration (tmax) 4.0 h while in the group that received Manix® alongside pefloxacin Cmax was (0.22±0.08) µg/mL at tmax 1.0 h respectively. The area under curve of pefloxacin alone was (7.83±5.14) µg/h/mL while with Manix® was (2.60±0.08) µg/h/mL. There was a significant difference between Cmax, tmax and area under curve between pefloxacin alone and pefloxacin after Manix® pre-treatment (P<0.05).</p><p><b>CONCLUSIONS</b>The concurrent use of Manix® and pefloxacin has been found to compromise the therapeutic effectiveness of pefloxacin which could lead to poor clinical outcomes in patients.</p>
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The lipid profile studies of garlic, antioxidant vitamins C and E on pefloxacin-induced toxicity in wistar rat was evaluated. Method: One hundred adult wistar rats (120-180), of either sex were randomly selected into five study groups. Each group comprised of 10 pairs (ten males and ten females) were not allowed to mate, with group 1 as control. Group 11 were pefloxacin treated only while group 111 to 1V were pefloxacin treated with either garlic, vitamins C and E. Pefloxacin, garlic vitamin C and E in doses 11.43mg/kg, 4.28mg/kg, 14.29mg/kg body weight in normal saline (vehicle) was administered orally by intubation to male and female of groups 11 to V for 14 days. Control animals received 0.5ml of normal saline. In life observation measurements were taken and at the end of drug, garlic, antioxidant vitamins C and E combined administration animals were sacrificed and tissues obtained for biochemical assessment. Result: Physical signs of toxicity and ameliorating effects of antioxidant vitamins and garlic were also expressed in rats, pefloxacin treatment induced significant (P<0.05) increase in total cholesterol, low density lipoprotein, very low density lipoprotein, triacylglycerol and decrease in high density lipoprotein relative to control but PF exposed and antioxidant vitamins C, E and garlic treated groups produced significant (P<O.O5) reduction in TC, LDL, VLDL, TG and with an increase in HDL levels relative to PF only treated groups were observed. Conclusion: These results suggest adverse effect of pefloxacin and ameliorating role of garlic, vitamins C and E on wistar rats’.
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The Haematological studies of garlic, antioxidant vitamins C and E on pefloxacin-induced toxicity in wistar rat was evaluated. Method: One hundred adult wistar rats (120-180), of either sex were randomly selected into five study groups. Each group comprised of 10 pairs (ten males and ten females) were not allowed to mate, with group 1 as control. Group 11 were pefloxacin treated only while group 111 to 1V were pefloxacin treated with either garlic, vitamins C and E. Pefloxacin, garlic vitamin C and E in doses 11.43mg/kg, 4.28mg/kg, 14.29mg/kg body weight in normal saline (vehicle) was administered orally by intubation to both male and female of groups 11 to V for 14 days. Control animals received 0.5ml of normal saline. In life observation measurements were taken and at the end of drug, garlic, antioxidant vitamins C and E combined administration animals were sacrificed and tissues obtained for biochemical assessment. Result: Physical signs of toxicity and ameliorating effects of antioxidant vitamins and garlic were also expressed in rats, significant (p<0.05) decrease in Hb, PCV, RBC and Total WBC were observed. Conclusion: These results suggest adverse effect of pefloxacin and ameliorating role of garlic, vitamins C and E on wistar rats’.
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The aim of the study was to assess the pharmacokinetic and biopharmaceutical effect of ascorbic acid (Vitamin C) on pefloxacin on concurrent administration in man through urine excretion data and microbiological evaluation. A two way crossover study was performed in ten healthy male volunteers aged (Mean ± SD) 45 ± 5.5 years and weight (Mean ± SD) 75.4 ± 12.5 Kg recruited and given pefloxacin 400mg as single dose and urine samples collected and pooled up at time intervals. The drug was concurrently given with 500mg vitamin C after a washout period of 4 weeks and urine samples similarly collected. Urine samples collected were analyzed and pefloxacin concentrations were determined with UV spectrophotometer from a validated calibration curve. The pharmacokinetic parameters Cmax, tmax, Ke and t1/2 were determined and compared. Microbial evaluation of the interaction of the drugs was performed through MIC determination using urinary isolate S. aureus (U-11420). The ke for pefloxacin alone was significantly lower than that for pefloxacin concurrently administered with vitamin C (0.1hr-1 and 0.3hr-1) P<0.05. The amount of pefloxacin excreted was significantly lower on single administration of pefloxacin compared to the co-administration with vitamin C, (44.13mg against 141.99mg) at P<0.05. The MIC obtained against S. aureus was 0.025mg/ml for pefloxacin alone while the co-solution with vitamin C at below 2hr and 4hr impregnation period was 0.05mg/ml and 0.1mg/ml respectively. There was significant chemical, microbiological and biopharmaceutical interaction on co-administration of pefloxacin with vitamin C.
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The pharmacokinetics of orally administered pefloxacin were studied to evaluate the bio-enhancing effect of the herbal bio-enhancer, trikatu, in mountain Gaddi goats (n = 6). The findings of the study revealed a decreased plasma concentration (p > 0.05) of pefloxacin following trikatu administration during the absorption phase (10, 15, 20 min post pefloxacin administration). In contrast, the plasma concentrations of pefloxacin were significantly higher at 4, 6, 8 and 12 h (during the elimination phase) of the pefloxacin administration. The findings of the investigation revealed higher values for the area under the curve, the area under the first moment of the plasma drug concentration time curve, the mean residential time, the total duration of pharmacological action and bioavailability. Trikatu treatment, however, significantly reduced the elimination half life (t(1/2beta)) and zero time intercept of the elimination phase. The apparent volume of distribution based on the total area under the plasma drug concentration curve [(Vd((area))] and the apparent volume of distribution based on the zero time plasma concentration intercept of the elimination phase [Vd((B))] were significantly higher in trikatu treated animals indicating a better penetration of the drug. Based on the MIC of 0.8 microgram/ml of pefloxacin, a priming dose of 6.0 mg/kg and a maintenance dose of 2.21 mg/kg is required to be administered at 8 h intervals. For practical purposes in goats this would mean a priming dose of 6 mg/kg and a maintenance dose of 2 mg/kg given by the oral route, to be repeated at 8 h intervals.
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Animals , Administration, Oral , Anti-Bacterial Agents/administration & dosage , Biological Availability , Cross-Over Studies , Zingiber officinale , Goats/metabolism , Herb-Drug Interactions , Pefloxacin/administration & dosage , Phytotherapy/veterinary , Piper , Piper nigrum , Plant Extracts/pharmacologyABSTRACT
BACKGROUND: At the neuromuscular junction, pefloxacin (P) may exacerbate myasthenia gravis and reduce the tau of MEPC. So here we investigated the effect of P on the neuromuscular blocking action of rocuronium (R). METHODS: Hemidiaphragm-phrenic nerve preparations were obtained from male Sprague-Dawley rats (150-250 g). Preparations were bathed in Kreb's solution (in (mM): NaCl 118, KCl 5, CaCl2 2.5, NaHCO3 30, KH2PO4 1, MgCl2 1 and glucose 11), maintained at 32oC and then aerated with a mixture of 95% O2 and 5% CO2. Isometric forces generated in response to 0.1 Hz, and, 50 Hz for 19 seconds with supramaximal electrical stimulation(0.2 msec, rectangular) to the phrenic nerve, were measured with a force transducer. Single twitch tension (ST) and peak tetanic tension (PTT) were calculated as % reduction versus the control, and tetanic fade (TF), as a % increase. Each preparation was exposed to one of 4 P concentrations of Krebs' solution (0, 0.25, 0.5, 1.0 mM), and enough R solution was added to the tissue bath to achieve the desired R concentration. The effects of P and R were allowed to stabilize before measuring tension parameters. EC5, EC25, EC50, EC75, and EC95 of R for ST, PTT and TF were calculated using a probit model. The interactions between the two drugs were drawn with Berenbaum's additive isobole at 25% isobole, 50% isobole, and 75% isobole. Differences between EC50's of R according to P concentrations were tested by one way ANOVA with Tamhane for post hoc; P <0.05 was regarded as significant. RESULTS: The cumulative concentration-effect curves shifted to the right in ST, and to the left in TF as the concentration of P was increased. The interactions between these two drugs varied from additive to antagonistic according to the magnitude of relaxation effect, drug concentration, and the frequency of stimulation. CONCLUSIONS: P augmented the TF of R. Our results suggest that simultaneous 0.1 Hz and 50 Hz stimulations allow the neuromuscular blocking action of a drug to be correctly evaluated.
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Animals , Humans , Male , Rats , Baths , Drug Interactions , Glucose , Magnesium Chloride , Myasthenia Gravis , Neuromuscular Blockade , Neuromuscular Junction , Pefloxacin , Phrenic Nerve , Rats, Sprague-Dawley , Refractory Period, Electrophysiological , Relaxation , TransducersABSTRACT
BACKGORUND: Kanamycin (K) has been shown to block neuromuscular transmission by reducing acetylcholine release or postsynaptic action. Pefloxacin (P) may exacerbate myasthenia gravis and reduce the tau of MEPP. Rocuronium (R) is still the subject of dispute as to whether it has a selective presynaptic effect. Therefore, we undertook to compare the muscle relaxation actions and reversibilities of K, P and R. METHODS: Hemidiaphragm-phrenic nerve preparations were obtained from male Sprague-Dawley rats (150-250 g). Preparations were bathed in Krebs' solution ([mM]:NaCl 118, KCl 5, CaCl2 2.5, NaHCO3 30, KH2PO4 1, MgCl2 1 and glucose 11), maintained at 32degreeC and aerated with a mixture of 95% O2 and 5% CO2. isometric forces generated in response to 0.1 Hz, and 50 Hz for 1.9 seconds with supramaximal stimulation (0.2 ms, rectangular) to the phrenic nerve, were measured using a force transducer. The effects on single twitch tension (ST) and peak tetanic tension (PTT) were calculated as % reduction. The effects on tetanic fade (TF) were calculated as % increase. K, P and R were added to the tissue bath to achieve the desired bath concentrations. EC5, EC25, EC50, EC75, and EC95 for ST, PTT and TF were calculated using a probit model. The antagonism indices of neuromuscular blockades by calcium (5 mM), 3,4-diaminopyridine (3,4-DAP) (10muM), and neostigmine (N) (250 nM) were assessed at 85+/-5% reduction (or increase). RESULTS: The potencies of ST, PTT and TF were 5.49, 5.73 and 6.30 (mM) for K, 1.90, 1.67 and 1.31 (mM) for P, and 10.81, 5.27 and 4.41 (muM) for R. The correlation between ST, PTT and TF varied for K, P and R. Neuromuscular blockades of K were reversed similarly by calcium and 3,4-DAP, and partially by N, whilst those of P were not, and ST reduction of R was reversed by 3,4-DAP (98%) and PTT and TF of R were partially reversed by 3,4-DAP and N. CONCLUSiONS: it is considered probable that K inhibits acetylcholine release and noncompetitively blocks postsynaptic sites, P postsynaptically depresses the neuromuscular transmission with acetylcholine receptor-ion channel block and that R has not only a selective presynaptic effect but also a postsynaptic block effect.
Subject(s)
Animals , Humans , Male , Rats , Acetylcholine , Baths , Calcium , Dissent and Disputes , Glucose , Kanamycin , Magnesium Chloride , Muscle Relaxation , Myasthenia Gravis , Neostigmine , Neuromuscular Blockade , Pefloxacin , Phrenic Nerve , Rats, Sprague-Dawley , Refractory Period, Electrophysiological , TransducersABSTRACT
OBJECTIVE:To discuss the economic efficiency of different antimicrobials in treatment of lower respiratory tract infections(LRTI) METHODS:50 cases of LRTI collected from this hospital were divided into two groups:A,pefloxacin;B,ceftazidime Evaluation was carried out with pharmacoeconomic cost-effectiveness analysis RESULTS:The total costs were 957 60 yuans and 1 596 00 yuans and the effective rates were 84% and 92% in group A and B respectively An increase of 1%effective rate in group A saved 79 80 yuans in comparison with that in group B CONCLUSION:The therapeutic scheme of pefloxacin seems to be the best one for treating LRTI
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The authors report a case of Campylobacter fetus subsp. fetus gastro-intestinal infection and bacteremia with poly-arthritis, mainly of the hip, in a French patient simultaneously suffering from cirrhosis of the liver. The outcome was eventually favorable, however only after a trial of ineffective pefloxacin-gentamicin therapy. The authors suggest: (i) gentamicin should not be given alone in C. fetus subsp. fetus infections, and (ii) pefloxacin should not be given if antibiotic sensitivities data are not available. The inconclusive reliability of disk diffusion tests for C. fetus subsp. fetus should be recognized.