Centralized national ethical review of clinical trials in Croatia.

Aim: To present the Croatian system of ethical review of clinical trials and assessment outcomes of the applications reviewed by the Croatian Central Ethics Committee.

Methods: Clinical trial applications reviewed by the Croatian Central Ethics Committee, which has the legal mandate to review clinical trials of medicinal products and medical devices, were retrospectively analyzed from May 2004 to the end of 2008 according to the number, research area, and type of opinion issued. Applications from 2008 were analyzed separately according to the study phase, participants (adult trials vs pediatric trials), and sponsor (commercial trials vs academic trials).

Macromolecular prodrugs. IX. Synthesis of polymer-fenoprofen conjugates.

Synthesis of several polymer-fenoprofen conjugates is described. Fenoprofen was first chemically modified into benzotriazolide 2 and amino acid amide derivatives: glycine fenoprofenamide (3a) and beta-alanine fenoprofenamide (3b) and their benzotriazolides 6a and 6b. Compounds 2 and 6 readily reacted with polyhydroxy aspartamide-type polymers, i.

Gemfibrozil ester and amide derivatives--synthesis, spectroscopic characterisation and QSPR.

The synthesis and spectroscopic characterisation of various gemfibrozil esters 3 and amides 4 are described. In the first step gemfibrozil was reacted with N-1-benzotriazolecarboxylic acid chloride (1) yielding gemfibrozil benzotriazolide (2). Compound 2 readily reacted with alcohols and amines to form the corresponding esters 3 and amides 4, potential prodrugs of the well known hypolipaemic drug gemfibrozil.

Macromolecular prodrugs. VIII. Synthesis of polymer-gemfibrozil conjugates.

Gemfibrozil is covalently linked to two similar polymers: poly[alpha,beta-(N-2-hydroxyethyl-DL-aspartamide)] and poly[alpha,beta-(N-3-hydroxypropyl-DL-aspartamide)]. The synthesised polymer drug conjugates differ in average molecular mass, type of covalent bonding, length of spacer, drug-loading and solubility.