In Process Citation

The novel excipient, sodium N-[8-(2-hydroxybenzoyl)amino]caprylate (SNAC, CAS 203787-91-1) increases the oral bioavailability of co-formulated ibandronate (IBN, CAS 138926-19). The aim of this study was to investigate the effect of the IBN/SNAC formulation on the steady-state pharmacokinetics of metformin (CAS 657-24-9) and to assess safety and tolerability of IBN/SNAC when dosed in combination with metformin. Twenty-two healthy subjects received metformin on Days 1 to 6. On Day 7, subjects received metformin together with the IBN/ SNAC formulation. The safety and tolerability of IBN/SNAC co-administered with metformin was consistent with the known safety profile of the single medications. The increase in mean maximum plasma concentration (Cmax) and mean overall exposure to metformin (AUC0-tau,) was approximately 7%. The entire 90% confidence intervals for the AUC- and Cmax-ratios did fall within the acceptance region for bioequivalence (0.8-1.25). In summary, administration of the IBN/ SNAC formulation together with metformin did not lead to a significant increase in exposure to metformin. The study medication was well tolerated in healthy volunteers.     

In Process Citation

This double-blind dose-response crossover study was designed to compare the efficacy and tolerability of sustained-release (SR) and conventional diltiazem over 4 weeks in patients with stable angina pectoris. Following a 2-week placebo run-in period, 26 patients were randomised into 3 parallel groups to receive either diltiazem SR (180, 240 or 300mg once daily) or conventional diltiazem 60mg three times daily for 2 weeks. Treatments were then crossed over for a further 2-week study period. Antianginal efficacy was evaluated using submaximal treadmill exercise testing. At baseline, all 3 treatment groups were comparable for all parameters. Treatment with both conventional and SR formulations improved exercise time and reduced intensity of ischaemia, but the difference between groups at the end of each 2-week treatment phase was not statistically significant. The results did not suggest a dose-response relationship. Adverse reactions necessitated treatment discontinuation in two patients being treated with conventional diltiazem and in one patient receiving diltiazem SR 240mg. In conclusion, this study demonstrated that diltiazem SR 180, 240 and 300mg did not differ from the conventional formulation in terms of anti-ischaemic efficacy.     

In Process Citation

The development of oncological therapeutic agents is a complex and risky process and it is mainly pursued by research-based pharmaceutical companies. Academic and public research institutions, however, have contributed to the finding and evaluation of basic scientific knowledge, which were transferred to the industry for co-development. Since 1960 increasing regulatory demands have caused a prolonged development time and dramatical multiplication of costs. Oncological research in Germany began shortly after the end of war, when Bayer worked on the ethyleneimino compounds with agents like E39 and trenimon for therapeutical use. Early in the fifties this focus of research changed to Asta-Werke, Bielefeld (later ASTA Medica, Frankfurt) where cyclophosphamide (Endoxan, Cytoxan), ifosfamide (Holoxan, Ifex) and trofosfamide were developed as worldwide leading alkylating cytotoxic agents. The detection of mesna (Uromitexan, Mesnex) used for the organospecific detoxification of urotoxic metabolites caused a further increase of the cancerotoxic selectivity and an improved safety of oxazaophosphorine therapy. There has been ongoing research on alkylating agents (mafosfamide, glufosfamide), and new therapeutic principles like miltefosine (Miltex) or hormonal agents like cetrorelix (LHRH-antagonist) are in development.