Klinische Untersuchungen zur Pharmakokinetik von Thiaminderivaten
The main topic of the thesis is dedicated to the description of the pharmacokinetics of thiamin after a single oral administration of either 100 mg thiamin nitrate or 100 mg S-benzoylthiamin-O-monophosphate (BTMP), a synthetic thiamin prodrug. In each case, ten patients with terminal renal insufficiency received the test dose after an overnight fast. Pharmacokinetic parameters are given (AUC, Cmax, tmax, oral and renal clearance). A complex representation of the distribution and interaction of thiamin and its phosphoric acid esters in blood, plasma, and erythrocytes was achieved with the aid of an open multi-compartment model including submodels. The apparent volumes of distribution, the mean residence time and the distribution and/or elimination rate constants were derived from the model. In another paragraph, the relative bioavailability of thiamin after a single intramuscular injection of 100 mg thiamin hydrochloride and/or a single oral application of 150 mg BTMP in the blood and the cerebrospinal fluid is described. In context of a post-marketing surveillance study, forty-two patients of a neurological hospital unit were given the test dose.