As expected from previous studies about the pharmacokinetics and biodisposition of different PVAs [30,31], in the present investigation, short-chained PVA was completely harmless in vivo during an observation VX-770 time of 4 h. The authors gratefully acknowledge the excellent technical assistance by Angela Wensing. Furthermore, the authors would like to thank Tanja Hinkeldein from the Department of Nephrology of the University Hospital Essen for help with the frozen section procedure and the team of the department of Pathology of the University Hospital Essen for hematoxylin–eosin staining of histological sections. “
“Prodrugs are compounds that
undergo a biological transformation prior to achieving their pharmacological effect and have been known for more than 50 years [1]. According to this definition, prodrugs are xenobiotics that are inactive per se, but are transformed into one or more active metabolites [ [2], [3] and [4]]. Although there is no universal definition of a prodrug, recent definitions also describe prodrugs as bioreversible derivatives
of active drug molecules that undergo enzymatic and/or chemical transformation in vivo to produce the pharmacological active compound, which can then exert the intended pharmacological effect [ 5, 6]. Ideally, the prodrug should be converted to the active parent compound, followed by a subsequent rapid elimination of the released promoiety [ 7]. Furthermore, it has been suggested that prodrugs should either be inactive or much less potent (1000-times) than the parent MS-275 cell line drug [ 8]. Different functional groups are amenable to
prodrug design, as recently reviewed [ 9]. In both drug discovery and drug development, the design of prodrugs is an established tool for improvement of the physicochemical, biopharmaceutical, and/or pharmacokinetic properties of pharmacologically active compounds. Prodrugs have been applied in a number Abiraterone of different situations to overcome various barriers to drug formulation and delivery, including poor aqueous solubility [ 10, 11], chemical or metabolic instability [ 12], insufficient absorption [ [13], [14] and [15]], local delivery as nasal [ 16] and lymphatic transport [ 17]. In 2004, Stella estimated that 5–7% of drugs worldwide could be classified as prodrugs [ 18] and in 2009, 13 of the 100 top-selling pharmaceuticals were prodrugs [ 4], including the statins, Mevacor® and Zocor®, which are cyclic prodrugs that have to be metabolised to the acyclic form that acts as the active compound [ 3]. Utilization of the prodrug approach may provide a life cycle management option for established drugs and thus the application of the concept is intriguing but also challenging. Despite similarity to the established drug the prodrug must be considered as a new chemical entity and its development planned and conducted accordingly.