Single shot of 17D vaccine may not confer life-long protection against yellow fever

The yellow fever (YF) vaccine has been used since the 1930s to prevent YF, which is a severe infectious disease caused by the yellow fever virus (YFV), and mainly transmitted by Culicidae mosquitoes from the genera Aedes and Haemagogus . Until 2013, the World Health Organization (WHO) recommended the administration of a vaccine dose every ten years. A new recommendation of a single vaccine dose to confer life-long protection against YFV infection has since been established. Recent evidence published elsewhere suggests that at least a second dose is needed to fully protect against YF disease. Here, we discuss the feasibility of administering multiple doses, the necessity for a new and modern vaccine, and recommend that the WHO conveys a meeting to discuss YFV vaccination strategies for people living in or travelling to endemic areas.

Pharmacokinetics and safety of repirinast tablets in healthy Chinese subjects

ABSTRACT Repirinast is a new, synthetic, disodium cromoglycate-like antiallergic agent for oral administration in humans. This study evaluated the safety, tolerability and pharmacokinetics of repirinast tablets in healthy Chinese volunteers. This was a phase I, open-label, randomized, single- and multiple-dose study. Subjects were assigned to receive a single dose of repirinast tablet at either 150, 300, or 450 mg, or multiple doses of 150 mg twice daily for 5 days. Plasma samples were analyzed with LC-MS/MS. Pharmacokinetic parameters of active metabolite MY-1250 (deesterified repirinast) were calculated using non-compartmental analysis with WinNonlin software. Statistical analysis was performed using SPSS software. All adverse events (AEs) were mild and of limited duration. No serious adverse event (SAE), death or withdrawal from the study was observed. In the single-dose study, Cmax was reached at about 0.75 hour, and the mean t1/2 was approximately 16.21 hours. Area under curve (AUC) and Cmax increased with dose escalation, but dose proportionality was not observed over the range of 150 to 450 mg. In the multiple-dose study, the steady-state was reached within 3 days with no accumulation. Repirinast tablet was well tolerated in healthy Chinese subjects.

Comparative Analysis of In-use Period after First Opening or Reconstitution of European Union Imported Sterile Products and Domestic Sterile Products in Our Hospital / 中国药师

Objective: To provide reference and suggestions for improving the in-use period information of sterile products after first opening or reconstitution in China. Methods: The package inserts of sterile products in our hospital were investigated. The sterile products needed to be reconstituted before use and with multiple-dose package were selected. The in-use period information of European imported sterile products and domestic sterile products were comparatively analyzed. Results: The presentation rate of in-use period in the package inserts of domestic sterile products was 32. 25% , which was less than 55. 56% of the other imported sterile products, and significantly less than 93. 55% of European imported sterile products. Conclusion: The relevant content of in-use period of sterile products after first opening or reconstitution is supplemented relatively late in China's stability testing guidance for drug substances and products, moreover, the specific technical proposals are absent. It is suggested that the drug administrative department and its techni-cal supportive agencies should improve the relevant guidance and guide pharmaceutical research enterprises and manufacturing enterpri-ses to carry out in-use stability studies, furthermore, gradually improve the relevant in-use period information in package inserts.

Intensive Insulin Therapy in Type 1 Diabetes / 임상당뇨병

The Epidemiology of Diabetes Interventions and Complications study, a prospective observational follow-up of the Diabetes Control and Complications Trial cohort, reported persistent benefits for micro- and macro-vascular complication in type 1 diabetes mellitus with intensive insulin therapy. It is the standard of care for most patients with type 1 diabetes. There are two modalities: continuous subcutaneous insulin infusion (CSII), so called insulin pump, and multiple dose of insulin. Both shows similar effects in frequency of severe hypoglycemia and progression of microvascular disease, but CSII provides slightly better in glycemic control. An important aspect of intensive insulin therapy is educating patients about basal insulin, and carbohydrate/insulin ratio, sensitivity index, the coordination of meals, activity, stress, and hormonal changes with frequent monitoring of blood glucose levels during pregnancy. It is important to identify and resolve emotional and attitudinal barriers of the patient and family for improving glycemic control during intensive diabetes management.

Steady-State Pharmacokinetic Properties of Tamsulosin in Healthy Male Volunteers

BACKGROUND: To evaluate the pharmacokinetic properties of daily oral doses of tamsulosin administered to fasted healthy Korean male volunteers for 5 days. METHODS: In a randomized, open-label, multiple-dose, two-period, crossover study, all 44 subjects were randomly assigned in a 1:1 ratio to receive a newly developed generic capsule formulation (test) or a branded capsule formulation (reference) of tamsulosin 0.2 mg, followed by a 10-day washout period and administration of the other formulation. Plasma concentrations of tamsulosin were assessed after administration of five-day multiple doses, using HPLC-MS/MS. Clinical and laboratory adverse events (AE) were assessed. RESULTS: The mean (SD) pharmacokinetic properties with the test and reference formulations were as follows: Css,max, 9.0 (2.9) and 8.4 (2.6) ng/mL, respectively; median (range) tmax, 4 (2-6) and 5 (2-7) hours; AUCtau, 93.7 (31.5) and 88.2 (29.3) ng x h/mL; and t(1/2), 9.5 (2.6) and 10.0 (2.7) hours. The volume of distribution and clearance after oral administration of tamsulosin were 0.5 L/kg, and 0.04 L/h/kg, respectively. The accumulation ratios for 0.2 mg once-daily dosing regimen were 1.2. The 90% CIs of the geometric mean ratios for the log-transformed AUCtau (1.005-1.131) and Css,max (1.000-1.136) values were within the acceptable range for bioequivalence. No serious AE was reported during the study. Both formulations were well tolerated. CONCLUSION: The results demonstrate that the Css,max and AUCtau values in the fasted subjects were higher than those in the fed from other study, with a shorter tmax values.

Pharmacokinetics of faropenem sodium for injection after a single and multiple intravenous dose in healthy volunteers / 中国药理学通报

Aim To study the pharmacokinetics of faropenem sodium for injection after a single and multiple intravenous dose in 12 healthy volunteers.Methods Multiple-dose regiments used 12-hour dosing intervals for 5 doses.Plasma and urine faropenem sodium concentrations were measured using high-performance liquid chromatography.The concentration-time curves of faropenem sodium were fitted to a two-compartment open model.The excretion data in urine were disposed by the method of excretion rate in urine.Results The pharmacokinetic parameters obtained from the single-dose study were as follows: C_(max) =(45.20±8.73) mg·L ~(-1); T_(1/2α) =(0.401±0.096) h; T_(1/2β) =(1.419±0.267) h;AUC_(0-12) =(59.216±11.886) mg·h·L~(-1) .The steady-state pharmacokinetic parameters were: C ss min =(0.03±0.02) mg·L~(-1) ; C ss max =(44.60±9.08) mg·L~(-1) ; C_(av)=(4.939±1.048) mg·L~(-1) ; T_(1/2α) =(0.340±0.105) h; T_(1/2β) =(1.257±0.173) h;AUC~(ss)_(0-12) =(59.268±12.571) mg·h·L~(-1) .The amount of cumulative recovery of faropenem sodium in urine for single and multiple dose within 12 h was(30.48±12.77)% and (40.55±17.53)%, respectively.The pharmacokinetic parameters in urine of the single-dose study were: T_(1/2) =(0.993±0.088) h, K_e=(0.227±0.097) h~(-1) .The steady-state pharmacokinetic parameters in urine were: T_(1/2) =(1.085±0.069) h, K_e=(0.296±0.136) h~(-1) .Conclusions The distribution and elimination rates of faropenem sodium for injection are not changed after multiple intravenous administrations.Effective concentrations in vivo can be achieved after the repeated administration with 400 mg twice a day regiment.The dosing schedule can be recommended.

Comparison of single-dose and multiple-dose systemic methotrexate treatment followed by aspiration curettage and local methotrexate injection in treatment of cervical pregnancy / 대한산부인과학회지

OBJECTIVE: To compare the clinical efficacy of systemic single-dose and multiple-dose methotrexate (MTX) regimens combined with aspiration curettage and local MTX in treatment of cervical pregnancy. METHODS: Between January 2000 and December 2006, 40 cases of cervical pregnancies were treated with combined systemic and local methotrexate therapy at the Department of Obstetrics and Gynecology, Chung-Ang University Hospital. The patients were treated with either of the two regimens:a) Single dose regimen (Group 1): 1 mg/kg of intramuscular MTX with leucovorin treatment (18 cases).b) Multiple dose regimen (Group 2): four doses of 1 mg/kg of intramuscular MTX with leucovorin treatment (22 cases). Combination treatment with aspiration curettage and local MTX injection were done in all patients after clinically indicated.Baseline characteristics, regimens used and number of doses administered, treatment outcome, presence and severity of side effects were analyzed. RESULTS: The mean age of the patients was 28+/-2.8 vs 28.4+/-2.4 years and gestational age at diagnosis was 49.4+/-8.3 vs 56.4+/-7.4 days. Initial level of serum beta-hCG ranges was 3,242.2+/-189.2 vs 2,864.3+/-172.4 IU/mL. There were no significant differences in initial beta-hCG values, gestational age between single-dose group and multiple-dose groups, The overall success rate of MTX management for an ectopic pregnancy was 82.5% (33/40) with 66.7% (12/18) and 95.5% (21/22) for single and multiple dose groups respectively. Multiple dose group had more rapid downward trend of hCG and more rapid stabilization. Side effects occurred in 20% (8/40) of the study group with 16.7% (3/18) and 22.7% (5/22) for single and multiple dose groups respectively but not significant. CONCLUSION: Systemic single-dose and multiple-dose MTX regimen combined with local MTX injection with aspiration curettage and local MTX injection is an effective and safe treatment modality for cervical pregnancies. In our study, multiple-dose regimen treatment is more effective, mild side effects comparable with single dose regimen. Further comparative studies with long-term follow-up are needed to evaluate reproductive outcome and to reduce side effects.

Contaminación extrínseca de soluciones parenterales y medicamentos en frascos multidosis / Extrinsic contamination of parenteral solutions and multiple-dose vials

Las infecciones nosocomiales ocurren durante las 48-72 horas después del ingreso a un centro de salud o luego de un periodo definido tras el alta, uno de los vehículos para este tipo de infección son las soluciones parenterales (SP) y los medicamentos en frascos multidosis (FMD). Se determinó la frecuencia de contaminación extrínseca de SP y FMD en algunos servicios de hospitalización del Complejo Hospitalario Universitario “Ruiz y Páez” en Ciudad Bolívar-Venezuela. Se analizaron 95 SP y 82 FMD para un total de 177 muestras, las cuales se cultivaron y los microorganismos aislados fueron identificados a través de pruebas bioquímicas convencionales. De las 177 muestras evaluadas, 42 (23,73%) presentaron crecimiento de microorganismos. El 27,36% de las SP y el 19,51% de los FMD resultaron contaminados. Los microorganismos más frecuentemente aislados fueron Bacillus sp. (55,30%), Candida albicans (14,88%) y Staphylococcus coagulasa negativos (8,52%). Se concluyó que durante el periodo estudiado en las soluciones parenterales predominó la contaminación por microorganismos ambientales, mientras que las levaduras predominaron en los frascos multidosis especialmente en los de sulfato de magnesio.

Nosocomial infections occur during the 48-72 hours after admission to a health centre or after a defined period after discharge, one of the vehicles for this type of infection are the parenterals solutions (PS) and parenteral drugs in multidose vials (MDV). We determinated the prevalence of extrinsic contamination of PS and MDV hospitalization in some services of the Hospital Universitario “Ruiz and Páez” in Ciudad Bolívar-Venezuela. We analyzed 95 PS and 82 MDV for a total of 177 samples, which were cultivated and isolated microorganisms were identified by conventional biochemical tests. Of the 177 samples tested, 42 (23.73%) had growth of microorganisms. The 27.36% of the PS and the 19.51% of MDV were contaminated. The most commonly isolated microorganisms were Bacillus sp. (55.30%), Candida albicans (14.88%) and coagulase negative Staphylococcus (8.52%). It was concluded that during the period studied in parenteral solutions prevailing contamination by environmental microorganisms, while yeast predominated in especially in multidose vials of magnesium sulfate.

Comparison of Clinical Progress between Single- and Multiple-dose Surfactant Treatment in Neonatal Respiratory Distress Syndrome / 소아과

PURPOSE: In the case of serious respiratory distress syndrome (RDS) or relapse of clinical appearances after single treatment, we obtained more effective results with multiple-dose surfactant replacement therapy. We carried out this investigation for comparing and observing clinical progress between single-dose (group S) and multiple-dose (group M) pulmonary surfactant treatment group of neonatal RDS. METHODS: We investigated 48 neonates who were diagnosed as RDS and treated with pulmonary surfactant (PS) replacement therapy in NICU of Kyunghee University hospital from January 2002 to March 2004, then we compared and verified clinical progress of 32 neonates in group S with that of 16 neonates in group M. RESULTS: There were no significant statistical differences in average birth weights, average gestational periods, initial pH values of birth, whether operation of resuscitation at that time of birth was made or not, whether prenatal steroid prescription for mother, RDS classification standardized by Bomsel, and ventilation index (VI) before instillation of PS of two groups. However, there was significant statistical difference in a/A PO2 (P< 0.05). We could observe changes of VI and a/A PO2 within 72 hours have been continuously improved at group S rather than group M. In spite of relapses, group M changed for the better after second dose. There were also no significant differences between the two groups in duration of ventilator therapy, mortality within 28 days after birth, intraventricular hemorrhage by complication, retinopathy of premature, necrotizing enterocolitis, chronic lung diseases, sepsis, and DIC. CONCLUSION: In these relapse cases, as there were no significant differences in the mortality rate and the occurence of complication between group S and group M, the requirement of multiple-dose PS replacement therapy which brought improvement of prognosis was emphasized.

A Study of Clinical Efficacy of GnRH Antagonist (Cetrorelix) Single and Multiple Dose Protocol for Controlled Ovarian Hyperstimulation / 대한불임학회지

OBJECTIVE: This study was performed to compare the clinical outcomes of GnRH antagonist (Cetrorelix) single dose and multiple dose protocols for controlled ovarian hyperstimulation with GnRH agonist long protocol. MATERIALS AND METHOD: From September 2001 to March 2002, 48 patients (55 cycles) were performed controlled ovarian hyperstimulation for ART using by either GnRH antagonist and GnRH agonist. Single dose of 3 mg GnRH antagonist was administered in 15 patients (17 cycles, single dose group) at MCD #8 and multiple dose of 0.25 mg of GnRH antagonist was administered in 15 patients (18 cycles, multiple dose group) from MCD #7 to hCG injection day. GnRH agonist was administered in 18 patients (20 cycles, control group) by conventional GnRH agonist long protocol. We compared the implantation rate, number of embryos, and clinical pregnancy rate among three groups. Student-t test and Chi-square were used to determine statistical significance. Statistical significance was defined as p<0.05. RESULTS: There were no significant differences in ampules of used gonadotropins, number of mature oocytes, obtained embryos between single and multiple dose group, but compared with control group, ampules of used gonadotropins, number of mature oocytes, obtained embryos were decreased significantly in both groups. Clinical pregnancy rate and implantation rate were not different in three groups. There were no premature LH surge and ovarian hyperstimulation syndrome in three groups. Multiple pregnancy were occurred 1 case in multiple dose group and 2 case in control group. CONSLUSIONS: GnRH antagonist is a safe, effective, and alternative method in the controlled ovarian hyperstimulation compared with GnRH agonist. Clinical outcomes and efficacy of both single and multiple dose protocol are similar between two groups.

A Study of Clinical Efficacy of GnRH Antagonist (Cetrorelix) Single and Multiple Dose Protocol for Controlled Ovarian Hyperstimulation / 대한불임학회지

OBJECTIVE: This study was performed to compare the clinical outcomes of GnRH antagonist (Cetrorelix) single dose and multiple dose protocols for controlled ovarian hyperstimulation with GnRH agonist long protocol. MATERIALS AND METHOD: From September 2001 to March 2002, 48 patients (55 cycles) were performed controlled ovarian hyperstimulation for ART using by either GnRH antagonist and GnRH agonist. Single dose of 3 mg GnRH antagonist was administered in 15 patients (17 cycles, single dose group) at MCD #8 and multiple dose of 0.25 mg of GnRH antagonist was administered in 15 patients (18 cycles, multiple dose group) from MCD #7 to hCG injection day. GnRH agonist was administered in 18 patients (20 cycles, control group) by conventional GnRH agonist long protocol. We compared the implantation rate, number of embryos, and clinical pregnancy rate among three groups. Student-t test and Chi-square were used to determine statistical significance. Statistical significance was defined as p<0.05. RESULTS: There were no significant differences in ampules of used gonadotropins, number of mature oocytes, obtained embryos between single and multiple dose group, but compared with control group, ampules of used gonadotropins, number of mature oocytes, obtained embryos were decreased significantly in both groups. Clinical pregnancy rate and implantation rate were not different in three groups. There were no premature LH surge and ovarian hyperstimulation syndrome in three groups. Multiple pregnancy were occurred 1 case in multiple dose group and 2 case in control group. CONSLUSIONS: GnRH antagonist is a safe, effective, and alternative method in the controlled ovarian hyperstimulation compared with GnRH agonist. Clinical outcomes and efficacy of both single and multiple dose protocol are similar between two groups.

Multiple dose methotrexate chemotherapy in suspected medical treament failure of ectopic pregnancy / 대한산부인과학회잡지

OBJECTIVE: The purpose of this study was to determine the efficacy of multiple dose methotrexate (MTX) chemotherapy approved as a primary treatment of ectopic pregnancy in suspected medical treatment failure of ectopic pregnancy. METHODS: This study included 77 hemodynamically stable high risk ectopic pregnants diagnosed from January 1995 to June 2000 at department of Obstetrics & Gynecology, Sanggye Paik hospital, Inje university. High risk criteria of our study were adnexal ectopic mass 3.5 cm or serum-hCG 4,000 mIU/ml or presence of fetal heart beat(FHB) or presence of peritoneal fluid and fresh blood on culdocentesis. Statistics were analyzed with 2-test, Student t-test and odds ratio of each risk factors. RESULTS: The response rate of multiple dose MTX chemotherapy was 85.7%(66/70). There was no statistically difference of risk factors between success and failure group except fetal heart beat. Among 11 failure patients, there were 3 patients with adnexal ectopic mass 3.5 cm (odds ratio=1.4, 0.3~5.7), 3 patients with presence of FHB, 7 patients with presence of peritoneal fluid(odds ratio=1.0, 0.3~3.8), 8 patients with serum-hCG 4,000 mIU/ml (odds ratio=2.8, 0.7~11.6). CONCLUSION: There results suggest that multiple dose MTX chemotherapy can be treated regardless of ectopic mass size, presence of pretoneal fluid, serum beta-hCG level. But we must pay attention to treat ectopic pregnancy with presence of fetal heart beat.