Association between genetic variants of transmembrane transporters and susceptibility to anthracycline-induced cardiotoxicity: Current understanding and existing evidence.

Anthracyclines remain the cornerstone of numerous chemotherapeutic protocols, with beneficial effects against haematological malignancies and solid tumours. Unfortunately, the clinical usefulness of anthracyclines is compromised by the development of cardiotoxic side effects, leading to dose limitations or treatment discontinuation. There is no absolute linear correlation between the incidence of cardiotoxicity and the threshold dose, suggesting that genetic factors may modify the association between anthracyclines and cardiotoxicity risk. And the majority of single nucleotide polymorphisms (SNPs) associated with anthracycline pharmacogenomics were identified in the ATP-binding cassette (ABC) and solute carrier (SLC) transporters, generating increasing interest in the pharmacogenetic implications of their genetic variations for anthracycline-induced cardiotoxicity (AIC). This review focuses on the influence of SLC and ABC polymorphisms on AIC and highlights the prospects and clinical significance of pharmacogenetics for individualised preventive approaches.

Retrospective analysis of tigecycline shows that it may be an option for children with severe infections.

AIM: This study assessed the efficacy and safety of tigecycline in children with life-threatening infections. METHODS: We retrospectively reviewed the clinical records of patients treated with tigecycline from June 2012 to May 2014 in a Chinese tertiary centre. RESULTS: The study comprised 24 patients (14 male) with a median age of four years (range, 50 days-12 years). The most frequently isolated microorganism, most common isolation site and type of infection were Acinetobacter baumannii, tracheal aspirate fluid and ventilator-associated pneumonia, respectively. Tigecycline was administered at a loading dose of 1.5 or 2.0 mg/kg and 1.0 mg/kg every 12 hours after that. The average duration of treatment was 11.6 ± 5.8 days. The clinical response and microbiological eradication rate were 37.5% and 29.2%, respectively. Six of the patients we studied (25.0%) died, and three of these deaths were considered to be infection related. Adverse drug reactions were identified in four patients (16.7%) during the treatment, including abnormal liver function, prolonged prothrombin time and diarrhoea. CONCLUSION: Our findings suggest that tigecycline may be an option for children with severe infections. However, more prospective, controlled trials are required to objectively evaluate the efficacy and safety of tigecycline in children.

Thymosin-loaded enteric microspheres for oral administration: preparation and in vitro release studies.

Thymosin, a water-soluble polypeptide compound, was encapsulated within enteric microspheres of acrylic acid resin II by modified oil in oil (o/o) emulsion solvent evaporation method. The mixture emulsifier composed of lecithin and Span 80 was critical to the formation of sphere-shaped thymosin microparticles. Optimizing process parameters, such as the volume ratio of organic solvent to water, initial drug feed and polymer concentration, resulted in high drug encapsulation efficiency of 89.7% (6% polymer concentration and 0.5% initial drug feed). In vitro release studies suggested that thymosin release from microspheres exhibited pH dependent profiles. For formulation with 6% polymer concentration and 0.5% initial drug feed, 68.7% thymosin was released within 4h in pH 6.8 PBS buffer, while only 6.5% was observed in acid medium.