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OBJECTIVE： To investigate the characteristics and regularity of hepatotoxicity induced by quinolones， and to provide reference for clinical use of drug safely. METHODS： Using “quinolone” “floxacin” “hepatotoxicity” “hepatic injury”as retrieval words， relevant literatures about hepatotoxicity induced by quinolones were retrieved from domestic and foreign databases as CNKI， Wanfang， VIP， PubMed （during database establishment to 31th， Dec. 2017）. Those literatures were summarized and analyzed. RESULTS： A total of 59 valid literatures were collected， including 61 cases of hepatotoxicity induced by quinolones， 8 types of drugs as ciprofloxacin， moxifloxacin， ofloxacin， lomefloxacin， norfloxacin， levofloxacin， gatifloxacin and enoxacin. Ciprofloxacin， levofloxacin， moxifloxacin and ofloxacin were the most common drugs that caused hepatotoxicity， involving 19， 13， 11， 7 cases， respectively； accumulative constitute ratio was 81.97％. The ratio of male to female was 1.54 ∶ 1， and hepatotoxicity always happened at the age of 61 to 80 （30 cases， 49.18％）. Primary diseases of 46 cases were single disease （75.41％）， and mainly were infection of respiratory system and urogenital system. There were 15 cases of combined disease （24.59％）. Thirty-one cases used quinolones alone， most of which was ciprofloxacin. There were 30 cases of drug combination. Thirty-four cases were given drug intravenously and mainly were domestic cases. The hepatotoxicity first occurred within 10 minutes after administration and at the latest 8 weeks after administration. Forty-nine patients suffered from hepatotoxicity within 10 days after medication， accounting for 80.33％. Besides general fatigue， nausea and vomiting， clinical symptoms also included abnormal elevation of alanine aminotransferase， aspartate aminotransferase and total bilirubin，etc. Fifty-four patients were improved after withdrawal or symptomatic treatment， while 7 patients died. The results of causality evaluation of drug-induced hepatic injury showed that there were 4 probably association cases， 45 likely association cases and 12 possible association cases. CONCLUSIONS： The hepatotoxicity caused by quinolones is related to drug variety， patient’s age， primary disease， drug combination and route of administration， and mostly occurs within 10 days after administration. Great importance should be attached to patient’s liver function indexes， strengthen medication monitoring， and carefully combined use of drugs.
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Objective: To compare the pharmacokinetics and bioavailability of pirfenidone in the fasted and fed states in healthy volunteers. Methods: An open-label, randomized crossover study was conducted in 12 healthy subjects. Food effects were examined by comparing pharmacokinetic data of pirfenidone after administration of a single oral 400 mg dose under fasted or fed conditions. Plas-ma pirfenidone concentration was determined by an HPLC method and its pharmacokinetic parameters were calculated with DAS v2. 0 software. Results: Under fasted and fed conditions, the concentration-time profiles of pirfenidone were fitted a one-compartment model and the pharmacokinetic parameters were as follows: t1/2were (2. 16 ± 0. 47) and (2. 05 ± 0. 42) h;tmaxwere(0. 69 ± 0. 16)and (1. 46 ± 0. 40)h;Cmaxwere (12. 95 ± 1. 79) and (9. 16 ± 2. 87) mg·L-1;AUC0-12were (44. 97 ± 15. 06) and (36. 19 ± 14. 44) mg·h·L-1;AUC0-∞were (46. 55 ± 16. 79) and (37. 41 ± 15. 43) mg·h·L-1, respectively. When compared with that of the fasted group, tmaxwas significantly increased (P<0. 001) while Cmaxand AUC were remarkedly decreased in the fed group (P<0. 001 and P<0. 01, respectively). Conclusion: Concomitant food intake significantly influences the pharmacokinetics and bioavail-ability of pirfenidone as indicated by reducing its extent and rate of absorption, which is associated with better tolerability.
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Objective:To investigate the clinical characteristics and causes of serotonin syndrome induced by tramadol in order to provide references for rational drug use in clinical practice. Methods:The relevant literatures published in domestic medical journals from the building of database to 2016 were retrieved in PubMed, EMbase, CNKI and WanFang database and statistically analyzed in respects of types and relevance evaluation of adverse drug reactions, the age and gender distribution of patients, the application of drugs,occurrence time of serotonin syndrome,clinical manifestations,treatment and outcome. Results:A total of 21 cases of seroto-nin syndrome induced by tramadol were collected. Totally 19 cases were caused by combined drug use, among which 12 cases were combined with selective serotonin reuptake inhibitors. The results of relevance evaluation showed 19 cases of possible relevance and 2 cases of probable relevance. Totally 10 cases of severe adverse drug reactions were reported and 11 cases of common adverse drug reac-tions were exhibited. One patient was heterozygous for CYP2D6 polymorphisms(CYP2D6?1/?4) causing decreased metabolizing a-bility to tramadol. Totally 28.6% of patients developed symptoms in 24h after the addition of new serotonergic agents or increase the dosage of serotonergic agents. In most cases,the patients' syndrome resolved with discontinuation of at least one serotonergic drug and symptomatic treatment,usually in less than one week. Conclusion:When prescribing tramadol,physicians should be aware of seroto-nin syndrome induced by drug-drug interactions and possible pharmacogenetic factors. It is important that safety monitoring should be carried out in patients during the application of drugs to reduce the harm of adverse drug reactions.
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Objective: To establish an HPLC-fluorescence detection method for the determination of thioguanosine-monophosphate (TGMP), thioguanosine-diphosphate (TGDP) and thioguanosine-triphosphate (TGTP) in red blood cells (RBC), as well as quantify the individual thioguanine nucleotides metabolites in kidney transplant recipients with azathioprine (AZA) therapy.Methods: The individual thioguanosine phosphates were extracted from RBC by dichloromethane and subsequently oxidized by potassium permanganate.The separation was achieved on a Nucleosil C18 column (150 mm×4.6 mm,5 μm) with an ion pairing reagent and detected by a fluorescence detector (excitation at 315 nm, emission at 390 nm).The mobile phase consisted of 20 mmol·L-1 potassium phosphate buffer (pH was adjusted to 6.8 by 5 mmol·L-1 tetrabutylammonium hydrogensulfate)-acetonitril (80:20) with the flow rate of 1.0 ml·min-1.Results: TGMP, TGDP and TGTP were quantified from RBC within the range of 50-500, 50-1000 and 100-5 000 pmol·ml-1, respectively.The limit of quantification (LOQ) was 50, 50 and 100 pmol·ml-1 RBC for TGMP, TGDP and TGTP, respectively.The intra-and inter-day RSDs were below 7.0% with the method recovery between 95.0% and 103.6%.The mean extraction recovery was above 90%.The assay was applied in the blood samples of 30 kidney transplant recipients with AZA therapy, and the results indicated that TGTP was the predominant phosphate metabolite in RBC.Conclusion: The method is simple, rapid, sensitive and specific, and it can quantitatively determine the individual thioguanosine phosphates in RBC of kidney transplant recipients with AZA therapy.
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Objective To investigate the entry points for clinical work of intensive care unit (ICU) pharmacists.Methods Through combination with daily work and referring the domestic and foreign literature,the characteristics of ICU medications were discussed to find out the entry point for clinical work of ICU pharmacists.Results ICU patients particularly need individualized pharmaceutical care because of the special pathophysiological characteristics and medicine use.Conclusion ICU pharmacists should provide pharmaceutical care based on Pharmacokinetics/pharmacodynamics knowledge and focus on the drug dosage adjustment,drug interactions and adverse event prevention.
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Objective To investigate the effects of Wuzhi capsules on tacrolimus concentration in heart transplant recipients and provide evidence for individualized dose optimization of tacrolimus.Methods Forty heart transplant recipients receiving Wuzhi capsules were enrolled in this study.Tacrolimus trough concentration was compared before and after coadminstration of Wuzhicapsules.Furthermore,polymorphisms of CYP3A4 * 1G and CYP3A5 * 3 were also detected to clarify correlations between genotypes and effects of Wuzhi capsule.Results Dose-normalized concentration of tacrolimus after coadministartion with Wuzhi capsules was 2.02-fold higher than before,the results of which was not associated with CYP3A4 * 1G and CYP3A5 * 3 genotypes.Wuzhi capsule could significantly decrease the total bilimbin (T-BiL),but not other hepatic and renal function.Conclusion Dose-normalized concentration of tacrolimus in heart transplant recipients is remarkably increased by Wuzhi capsule.The elevated trough levels rarely result in hepatic and renal toxicity.Wuzhi capsule is a safe,effective,and stable drug to increase the trough concentration of tacrolimus.
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Objective:To summarize the structure, properties and biological functions ofβ-glucuronidase. Methods:By referring to the relevant literatures at home and abroad onβ-glucuronidase in recent years, this paper induced, analyzed and drew conclusions. Results:The crystal structure of humanβ-glucuronidase is comprised of three distinct structural domains. The most common mutation of β-glucuronidase is missense mutation, which results in the change of enzyme activity, and then induces a series of pathological chan-ges like MPSⅦ. The researches on β-glucuronidase used in antibody-directed enzyme prodrug drug therapy and enzyme replacement therapy are becoming deeper and deeper. Conclusion:β-Glucuronidase as an important acid hydrolytic enzyme in human has a variety of genetic mutations, and plays an important role in the fields of medicine and disease diagnosis, which has become one of research hotspots.
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Objective:To summarize the structure, properties and biological functions ofβ-glucuronidase. Methods:By referring to the relevant literatures at home and abroad onβ-glucuronidase in recent years, this paper induced, analyzed and drew conclusions. Results:The crystal structure of humanβ-glucuronidase is comprised of three distinct structural domains. The most common mutation of β-glucuronidase is missense mutation, which results in the change of enzyme activity, and then induces a series of pathological chan-ges like MPSⅦ. The researches on β-glucuronidase used in antibody-directed enzyme prodrug drug therapy and enzyme replacement therapy are becoming deeper and deeper. Conclusion:β-Glucuronidase as an important acid hydrolytic enzyme in human has a variety of genetic mutations, and plays an important role in the fields of medicine and disease diagnosis, which has become one of research hotspots.
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OBJECTIVE:To investigate the clinical characteristics and gene polymorphism of oxcarbazepine (OXC)- induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). METHODS:Retrieved from CNKI,Wanfang,VIP, PubMed,EMBase,SpringerLink and other databases,case reports about OXC-induced severe ADR were summarized and ana-lyzed. RESULTS:Twelve literatures were collected,and 13 case reports about OXC-induced SJS/TEN were obtained. Male had more OXC-induced severe skin ADR than female. ADR mostly occurred during 1-14 d after medication. All patients were cured with treatment of glucocorticoid and antiallergy,without death case. Genotyping for 8 patients were performed and 6 of them showed the presence of HLA-B*1502 allele. While HLA-B alleles of 2 patients were HLA-B*1518/B*4001,which was the variation of HLA-B*1502. CONCLUSIONS:OXC-induced ADR should be monitored closely. Great importance should be attached to patient education and follow-up program. HLA-B*1502 gene detection should be performed to guide rational use of OXC and optimize clini-cal drug use plan.
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Background:Cold storage and ischemia-reperfusion injury of liver grafts are critical for the prognosis of patients undergoing liver transplantation. Establishing a stable cold storage and reperfusion animal model is a fundamental measure for related studies. Aims:To establish a modified isolated perfused rat liver model for comprehensive assessment of liver grafts in studies on preservation of liver grafts before transplantation. Methods:Twelve Sprague-Dawley rats were randomly allocated into two groups. Livers of rats in control group were retrieved and perfused immediately for 90 minutes without preservation. In experimental group,liver grafts underwent a 30-minute warm ischemia followed by 24-hour cold storage before ex vivo perfusion. The perfusate was collected dynamically for monitoring the levels of transaminases,electrolytes and pH value;the portal vein pressure of liver grafts was measured by pressure sensor,and the hepatic hydrogen peroxide (HPO)level was assessed by microprobe for free radicals. The bile production was recorded after the ex vivo perfusion;meanwhile,the levels of malondialdehyde (MDA)and superoxide dismutase (Cu/ Zn SOD),the histopathological changes and apoptosis of hepatocytes of liver grafts were examined. Results:Compared with the control group,the levels of AST and ALT,the portal vein pressure and the HPO level of liver grafts in experimental group were obviously increased throughout the perfusion. Furthermore,the bile production and level of Cu/ Zn SOD of liver grafts in experimental group were significantly decreased. The histopathological injury and hepatocytes apoptosis of liver grafts were milder in control group. Conclusions:The liver function and antioxidant effect were reduced in warm ischemic and cold preserved liver grafts. The modified isolated perfused rat liver model established in this study is useful for monitoring and evaluation of the cold storage and reperfusion injury in liver grafts.
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Objective:To assess the clinical use of dezocine injection. Methods:The application of dezocine injection in the in-patients during December 2015 and November 2016 in a hospital was statistically analyzed and evaluated from indications, dosage, treatment course and combined drug use, etc. Results:A total of 12847 patients with the age range of 0-97 and the average age of (49 ± 15. 6) years old were treated with dezocine injection. The top three departments using dezocine injection were orthopaedics (12. 70％), hand surgery (10. 30％) and liver surgery (9. 39％). Totally 132 patients were with overdose(1. 03％), and mainly in cardiac surgery. The medication course of 1042 patients was more than one week(8. 11％), which was too long, while most of the pa-tients were with tumor. Conclusion:The clinical use of dezocine injection in the hospital is basically reasonable. However, clinicians still need more training to minimize the risks involved in the process of clinical medicine application.
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Objective:To study the association of RAC1 gene polymorphisms with protein expression levels of Rac1-GTP. Methods:A total of 182 healthy Hans population in Hubei were recruited. The 4 tag-SNPs in RAC1 gene were genotyped by Real time TaqMan-MGB genotyping assay. And the Rac1-GTP protein levels in plasma samples from all participants were determined by enzyme linked immunosorbent assays ( ELISA ) . The distribution characteristics of Rac1-GTP expression levels were also analyzed. Furthermore,the expression levels of Rac1-GTP were compared among different genotypes of the 4 tag-SNPs in RAC1 gene. Results:The distribution of Rac1-GTP expression levels was positive skewed in healthy Chinese Hans population. The expression levels were significantly higher in females than in males (P0. 05). Different expression levels of Rac1-GTP were observed in different genotypes for rs702482 and rs10951982 (P0. 05). Conclusion:RAC1 genetic polymorphisms can potentially affect the expression levels of Rac1-GTP protein in healthy Chinese Hans population.
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Objective: To summarize the recent research progress in the influence of quercetin on drug metabolizing enzymes. Methods:By referring to the relevant literatures at home and abroad in recent years, the paper summarized, analyzed and concluded the the influence of quercetin on drug metabolizing enzymes. Results: Quercetin could modulate the phase Ⅰmetabolic enzyme cyto-chrome P450 ( CYP) and the phase Ⅱ metabolic enzymes uridine diphosphate - glucuronosyltransferase enzyme ( UGTs) , sulfotrans-ferase ( SULTs) and glutathione S-transferase ( GSTs) to influence the in vitro and in vivo metabolism of a lot of drugs. Meanwhile, the modulation of quercetin on the metabolic enzymes demanded the participation of various nuclear receptors. Conclusion:Quercetin shows the inhibitory or inducing effect on a variety of drug-metabolizing enzymes, therefore, it can interact with other drugs.
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Recently,the detection of circulating tumor cells(CTCs)in peripheral blood is used in clinical practice as a form of‘ liquid biopsy’. The self-seeding mechanism of CTCs provides a novel approach to explore the growing mechanism of malignant tumor and developing corresponding targeting therapies. A decade ago,the CellSearch system, which can capture and enumerate CTCs,has been validated by Food and Drug Administration( FDA)as an aid for monitoring the relapse of tumor after radical operation in patients with breast,prostate and colorectal cancer. In recent years,although the separation and detection technique of CTCs has been promoted significantly,the clinical significance of CTCs in tumors of digestive system is still under investigation. This article reviewed the research progress of peripheral blood CTCs in digestive system tumors.
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Objective:To develop a method for the detection of 10 single nucleotide polymorphisms(SNPs) of Nm23 gene,and to explore the genotypic and allelic distributions of the 10 SNPs in Chinese Hans population in Wuhan.Methods: Two hundreds healthy subjects ,115 men and 85 women included ,were enrolled as DNA sample donors.The real time TaqMan-MGB genotyping assay was used for the determination of the 10 SNPs selected ,and the results were validated by direct gene sequencing.Results:The method established could accurately and quickly screen the genotypes of the 10 SNPs of Nm23/NDPK gene.Distribution frequencies of the 10 SNPs were similar to these in other researches as well as these of HCB.All the loci follow the Hardy-Weinberg equilibrium.Highly linkage disequilibriums were found between rs 16949649 and rs7207370 , rs16949649 and rs34214448 , rs2159359 and rs2302254 , rs2159359 and rs8075231 ,rs2159359 and rs2041296 ,as well as rs2159359 and rs8071647 ,respectively.Four Tag SNPs:rs34214448 , rs2302254 ,rs11868380 and rs2318785 were initially selected by Heploview software.Conclusion:The method established for SNP gen-otyping can meet the needs for rapid analysis of Nm 23 gene polymorphisms ,and may have great values in investigating the association between gene polymorphisms and diseases as well as adverse drug reactions.
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Objective:To establish a method for the detection of 8 single nucleotide polymorphisms (SNPs) of RAC1 gene,and to analyze the genotypic and allelic distributions of the 8 SNPs in healthy Chinese Han population.Methods:The real-time fluorescence TaqMan-MGB probes allele classification technology was used for the determination of the 8 SNPs in 150 cases of healthy volunteers in Hubei China ,and the results were validated by direct gene sequencing.Results: The method established in this study can accurately screen the genotypes of the 8 SNPs of human RAC1 gene.Highly linkage disequilibriums were found between rs 10951982 and rs9374 , rs702482 and 836488 ,respectively.All the 8 sits were in accordance with Hardy-Weinberg equilibrium.Six Tag-SNPs were selected by Heploview software:rs10951982 ,rs6954996 ,rs6951997 ,r1s2977 ,rs702482 and rs702483.The MAFs of the 8 SNPs in our study were close to the MAFs in CHB and Asian in Hap Map database .Significant distribution differences were also observed in different races.Conclusion:No significant differences are observed in this study in healthy Chinese Han population.But differences are found when compared with the data of other races in Hap Map.
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A simple and sensitive liquid chromatographic method was developed for quantification of cefotetan disodium (CTT), a semi-synthetic cephamycin antibiotic, in human plasma. CTT and the internal standard chloramphenicol were extracted from plasma by a simple one-step protein precipitation with 35% (v/v) perchloric acid. Separation was carried out on a reverse-phase C18 column with a mobile phase of acetonitile-water containing 0.5% (v/v) phosphoric acids (20:80, v/v) at a flow rate of 1.0 mL/min. The column effluent was monitored by UV detection at 300 nm. The column temperature was maintained at 40°C. This method demonstrated good linearity in the range of 0.525-300.0 μg/mL, with correlation coefficients greater than 0.99. The limit of quantification (LOQ) was 0.525 μg/mL in human plasma. Intra- and inter-day precisions were less than 6.63% in terms of relative standard deviation (RSD). The accuracy, when expressed by the bias, ranged from 0.57% to 4.04%. The mean extraction recovery of CTT was higher than 40.94%. The method was found to be precise, accurate, and specific for CTT quantitative analysis, and was successfully applied for a pharmacokinetic study of CTT after a single intravenous dose of 1.0 g of CTT in healthy Chinese subjects.
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A simple and sensitive liquid chromatographic method was developed for quantification of cefotetan disodium (CTT), a semi-synthetic cephamycin antibiotic, in human plasma. CTT and the internal standard chloramphenicol were extracted from plasma by a simple one-step protein precipitation with 35% (v/v) perchloric acid. Separation was carried out on a reverse-phase C18 column with a mobile phase of acetonitile-water containing 0.5% (v/v) phosphoric acids (20:80, v/v) at a flow rate of 1.0 mL/min. The column effluent was monitored by UV detection at 300 nm. The column temperature was maintained at 40°C. This method demonstrated good linearity in the range of 0.525-300.0 μg/mL, with correlation coefficients greater than 0.99. The limit of quantification (LOQ) was 0.525 μg/mL in human plasma. Intra- and inter-day precisions were less than 6.63% in terms of relative standard deviation (RSD). The accuracy, when expressed by the bias, ranged from 0.57% to 4.04%. The mean extraction recovery of CTT was higher than 40.94%. The method was found to be precise, accurate, and specific for CTT quantitative analysis, and was successfully applied for a pharmacokinetic study of CTT after a single intravenous dose of 1.0 g of CTT in healthy Chinese subjects.
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Humans , Cefotetan , Blood , Pharmacokinetics , Chromatography, Liquid , MethodsABSTRACT
To determine the pharmacokinetics and bioequivalence of epinastine (EPN) hydrochloride, a promising histamine H1 receptor antagonist, in healthy Chinese volunteers under fasting conditions. METHODS: EPN hydrochloride test and reference tablets were administered as a single dose on two treatment days separated by a 1-week washout period. After dosing, serial blood samples were collected for a period of 36 h, and plasma EPN hydrochloride concentrations were determined by a validated reversed-phase HPLC method and pharmacokinetic parameters were calculated with DAS software. RESULTS: Plasma concentration-time profiles were adequately described by a two-compartment open model. The compound was rapidly absorbed and cleared slowly from plasma with a half-life of approximately 10 h. The main pharmacokinetic parameters of EPN hydrochloride test and reference tablets were as follow: tmax were (2.2±0.5) and (2.0±0.4)h, Cmax were (66±16)and (68±13)μg/L, t1/2 were(10.1±1.3) and (10.4±2.4)h, AUC0-36 were (592±88) and (601±94)μg·h·L-1, respectively. The relative bioavailability of test tablets was (99±13)%. CONCLUSION: The results indicate that the two formulations of EPN hydrochloride tablets are bioequivalent in the rate and extent of absorption.
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AIM: To compare the bioavailability of the test and reference formulation of secnidazole (2 g) tablets under fasting conditions. METHODS: This bioequivalence study was carried out in 20 healthy male Chinese volunteers according to a single dose, two-sequence, crossover randomized design. Fifteen blood samples per period were collected over 96 h, and plasma secnidazole concentrations were determined by locally validated high performance liquid chromatography (HPLC) assay and pharmacokinetic parameters were analyzed by the non-compartmental and compartmental methods. RESULTS: Plasma concentration-time profiles were adequately described by a one-compartment open model with first-order absorption. The main pharmacokinetic parameters of secnidazole test and reference tablets were as follows: tmax were (2.30±1.06) and (2.28±1.10) h, Cmax were (49.63±6.35) and (46.17±4.24) mg/L, t1/2 were (28.84±3.41) and (29.05±4.01) h, AUC0-96 were (1832.06±180.15) and (1847.14±204.14) mg·h-1·L-1, respectively. The relative bioavailability of test tablets was (99.99±11.92)%. CONCLUSION: The results indicate that the two formulations of secnidazole tablets are bioequivalent in the rate and extent of absorption.