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.

Objective To investigate the adverse drug reactions (ADRs) induced by escitalopram and precautions. Methods Wanfang,CNKI,Pubmed databases were searched to retrieve information about escitalopram adverse reactions reported in the literature,focusing on analysis of adverse reactions in patients with age,sex,clinical manifestations,involved systems, etc. Results Totally,31 references were collected,and a total of 31 cases included in the review analysis.The adverse reaction rate was equivalent between the male and the female.The adverse reaction occurred a few hours to 6 months after medication,and it involved several organ systems,including the nervous system,circulatory system,endocrine system,alimentary system,urinary system,kinetic system,etc. Conclusion Escitalopram should be used according to the doctor's advice,and its amount should not be arbitrarily added.Regular monitoring of adverse reactions should be performed to ensure rational use of the drug.

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.

Objective:To establish an FPLC-MS/MS method for the determination of fluvoxamine in human plasma. Methods:The separation was performed on an Inertsil? ODS-SP column(2. 1 × 100 mm, 3 μm). The mobile phase was acetonitrile-2 mmol· L-1 ammonium acetate (45: 55, v/v) containing 0. 1% formic acid at a flow rate of 0. 3 ml·min-1 . Lansoprazole was used as the internal standard( IS) . Electrospray ionization ( ESI) source was applied and operated in a positive ion model. Multiple reaction moni-toring (MRM) model with the transitions of fluvoxamine m/z 319. 1→m/z 69. 8 and lansoprazole m/z 370. 2→m/z 252. 1 was used to quantify fluvoxamine and IS, respectively. Results:In human plasma, the standard curve was linear within the range of 1-100 μg· L-1 . The lower limit of quantification of fluvoxamine( LLOQ) was 1μg·L-1 . The intra-day RSD was less than 5%, the inter-day RSD was less than 10%, and the method recovery was 85%-95%. Conclusion:The method is simple, sensitive, accurate and reproduci-ble. It is applicable in the pharmacokinetic study of fluvoxamine for clinical pharmacokinetics and bioequivalence studies.

Objective To explore the clinical manifestations ,risk factors and treatment of antibiotic asso-ciated diarrhea(AAD)in senile patients with severe bacterial pneumonia. Methods Retrospective analysis was made on senile patients of bacterial pneumonia combined with antibiotic associated diarrhea. Results There were 114 patients out of 572 cases had AAD. The incidence of AAD in these senile patients was 19.93%. There were 62.28% patients more than 80 years old. The incidence AAD was 37.3% with third generation cephalosporin treat-ment,28.6% penicillin with enzyme inhibitor treatment and 19.2% with carbopenems treatment. Conclusions The high risk factors of AAD in senile patients with bacterial pneumonia include patient′s age,and time, APACHE Ⅱ,category,combination therapyof antibacterial,and invasive operations. We should pay more atten-tion to AAD and related high risk factors when using these antibiotics in clinics. Rational selection and use of anti-bacterial are important measures to stop senile patients from ADD. Pharmaceutical care could help to optimize the treatment plan and reduce its adverse reaction of antibacterial in senile patients.

Objective:To establish an FPLC-MS/MS method for the determination of fluvoxamine in human plasma. Methods:The separation was performed on an Inertsil? ODS-SP column(2. 1 × 100 mm, 3 μm). The mobile phase was acetonitrile-2 mmol· L-1 ammonium acetate (45: 55, v/v) containing 0. 1% formic acid at a flow rate of 0. 3 ml·min-1 . Lansoprazole was used as the internal standard( IS) . Electrospray ionization ( ESI) source was applied and operated in a positive ion model. Multiple reaction moni-toring (MRM) model with the transitions of fluvoxamine m/z 319. 1→m/z 69. 8 and lansoprazole m/z 370. 2→m/z 252. 1 was used to quantify fluvoxamine and IS, respectively. Results:In human plasma, the standard curve was linear within the range of 1-100 μg· L-1 . The lower limit of quantification of fluvoxamine( LLOQ) was 1μg·L-1 . The intra-day RSD was less than 5%, the inter-day RSD was less than 10%, and the method recovery was 85%-95%. Conclusion:The method is simple, sensitive, accurate and reproduci-ble. It is applicable in the pharmacokinetic study of fluvoxamine for clinical pharmacokinetics and bioequivalence studies.

Objective To understand the clinical characteristics, treatment and prognosis of tenofovir (TDF)-induced Fanconi syndrome (FS).Methods The related databases were electronically searched for the cases of FS induced by TDF before November 2016.The related data of the patients were recorded and summarized.The results of detection of related laboratory parameters before and after the treatment for FS induced by TDF were compared.The clinical characteristics, and prognosis of FS induced by TDF were analyzed.The correlation of TDF and FS was analyzed by using Naranjo probability scale.Results A total of 59 cases were collected comprising 42 males (71.2%) and 17 females (28.8%) with age from 17 to 82 years, and the average age (46±13) years.The number of cases with human immunodeficiency virus (HIV) infection, hepatitis B virus (HBV) infection, and HIV with HBV infection were 48 (81.4%), 8 (13.6%), and 3 (5.1%), respectively.Eight patients (13.6%) were treated with TDF only, 51 patients (86.4%) were treated with TDF combined with other antiviral drugs.The top 3 of combined drugs were lopinavir/ritonavir (26 cases) , lamivudine (21 cases), and abacavir (14 cases).The dose of TDF was 300 mg/d in 24 patients with HIV infection, and 245 mg/d in 3 patients with HBV infection.The other patients′ dose of TDF was not reported.The time from medication of TDF to FS occurrence was 1 to 60 months in the patients with HIV infection, 3 to 45 months in the patients with HBV infection.The main clinical manifestations were diuresis (16 cases), polydipsia (10 cases), loss of weight (10 cases), fatigue (9 cases), and lower limb joint pain (8 cases), etc.The abnormities of laboratory parameters included increased serum creatinine concentration (51 cases), positive urine glucose (50 cases), positive urine protein (49 cases), decreased blood phosphate (46 cases), hypokalemia (23 cases), decreased blood bicarbonate (21 cases), increased blood urea nitrogen (12 cases), hypocalcemia (9 cases), and hyponatremia (9 cases), etc.The number of cases with acute renal failure, nephrogenic diabetes insipidus, osteoporosis, halisteresis, hypokalemic periodic paralysis, and stress fracture were 12, 7, 4, 3, 3, and 2, respectively.TDF was withdrawn in all patients after the occurrence of FS.The patients received the symptomatic treatments including intravenous hydration, supplement of potassium, phosphorus and calcium.Forty-five patients changed to use other antiviral drugs.Symptoms in 45 patients with FS were improved within 3 days to 5 months, and the laboratory indicators returned to normal within 2 weeks to 24 months.Thirteen patients′ serum creatinine concentration was still at high levels after drug withdrawal, prescription change, and 1 to 24 months of symptomatic treatments.A patient died from severe sepsis 2 months after drug withdrawal.The results of association analysis showed that FS in 11 patients (18.6%) were probably related to TDF and in 48 patients (81.4%) were possibly related to TDF.ConclusionsThe clinical manifestations of FS due to TDF are similar to primary FS.Most of the patients can return to normal after drug withdrawal and symptomatic treatment, some patients suffer irreversible renal damage.

Objective To understand the clinical characteristics, treatment and prognosis of tenofovir (TDF)-induced Fanconi syndrome (FS).Methods The related databases were electronically searched for the cases of FS induced by TDF before November 2016.The related data of the patients were recorded and summarized.The results of detection of related laboratory parameters before and after the treatment for FS induced by TDF were compared.The clinical characteristics, and prognosis of FS induced by TDF were analyzed.The correlation of TDF and FS was analyzed by using Naranjo probability scale.Results A total of 59 cases were collected comprising 42 males (71.2%) and 17 females (28.8%) with age from 17 to 82 years, and the average age (46±13) years.The number of cases with human immunodeficiency virus (HIV) infection, hepatitis B virus (HBV) infection, and HIV with HBV infection were 48 (81.4%), 8 (13.6%), and 3 (5.1%), respectively.Eight patients (13.6%) were treated with TDF only, 51 patients (86.4%) were treated with TDF combined with other antiviral drugs.The top 3 of combined drugs were lopinavir/ritonavir (26 cases) , lamivudine (21 cases), and abacavir (14 cases).The dose of TDF was 300 mg/d in 24 patients with HIV infection, and 245 mg/d in 3 patients with HBV infection.The other patients′ dose of TDF was not reported.The time from medication of TDF to FS occurrence was 1 to 60 months in the patients with HIV infection, 3 to 45 months in the patients with HBV infection.The main clinical manifestations were diuresis (16 cases), polydipsia (10 cases), loss of weight (10 cases), fatigue (9 cases), and lower limb joint pain (8 cases), etc.The abnormities of laboratory parameters included increased serum creatinine concentration (51 cases), positive urine glucose (50 cases), positive urine protein (49 cases), decreased blood phosphate (46 cases), hypokalemia (23 cases), decreased blood bicarbonate (21 cases), increased blood urea nitrogen (12 cases), hypocalcemia (9 cases), and hyponatremia (9 cases), etc.The number of cases with acute renal failure, nephrogenic diabetes insipidus, osteoporosis, halisteresis, hypokalemic periodic paralysis, and stress fracture were 12, 7, 4, 3, 3, and 2, respectively.TDF was withdrawn in all patients after the occurrence of FS.The patients received the symptomatic treatments including intravenous hydration, supplement of potassium, phosphorus and calcium.Forty-five patients changed to use other antiviral drugs.Symptoms in 45 patients with FS were improved within 3 days to 5 months, and the laboratory indicators returned to normal within 2 weeks to 24 months.Thirteen patients′ serum creatinine concentration was still at high levels after drug withdrawal, prescription change, and 1 to 24 months of symptomatic treatments.A patient died from severe sepsis 2 months after drug withdrawal.The results of association analysis showed that FS in 11 patients (18.6%) were probably related to TDF and in 48 patients (81.4%) were possibly related to TDF.ConclusionsThe clinical manifestations of FS due to TDF are similar to primary FS.Most of the patients can return to normal after drug withdrawal and symptomatic treatment, some patients suffer irreversible renal damage.

Objective:To evaluate the anti-infective therapy in a patient with multi-site infections after brain surgery and explore the role of clinical pharmacist in the treatment. Methods:With the applications of PK/PD characteristics of drugs and the coping strategies of resistant , vancomycin combined with fosfomycin were used to treat the intracranial infection caused by methicillin-resistant Staphylococcus epidermidis with vancomycin MIC of 2 mg·L-1 , and the dynamic adjustment of antibiotics was applied to treat the pulmonary infection caused by two kinds of pathogens including MDR bacteria. Results:The intracranial infection was successfully controlled, the pulmonary infection was also under control, and the overall condition of the patient was significantly improved. Conclusion: In the medical team, clinical pharmacists should make full use of their advantages in drug characteristics to carry out clinical pharmaceutical care.

A 45-year-old woman received an intravenous injection of levofloxacin( 0. 4 g,once daily),Suhuangzhike(苏黄止咳)capsules(3 capsules,thrice daily)by mouth,and montelukast sodium (10 mg at bedtime,once daily)by mouth for acute attack of chronic bronchitis. About 30 min after the first administration of montelukast sodium,the patient developed numbness of extremities and tremor,dyspnea, and generalized weakness,followed by nausea and vomiting and the symptoms lasted for about 2 hours without alleviating. Montelukast sodium was discontinued,levofloxacin and Suhuangzhike capsules were applied continuously,and symptomatic treatments were given at the same time. The numbness of extremities and tremor and dyspnea relieved,nausea and vomiting did not recur until 16 :00 of the following day.