The kinetics of vitamin E was followed in serum, liver and kidney of 10- and 55-day-old rats after the administration of a single i.m. dose of 100 mg alpha-tocopherol acetate/100 g body wt. The basal levels without vitamin E administration were significantly higher in serum and liver of 10- than 55-day-old rats. The effect of vitamin E on cisplatin (CP; 0.6 mg/100 g body wt., i.p.) nephrotoxicity was investigated by determining urinary volume and protein excretion, as well as the concentration of blood urea nitrogen (BUN) and lipid peroxides in renal tissue (LPO). Previously described age differences in CP nephrotoxicity were confirmed. The administration of vitamin E, 12 h prior to CP, diminished the toxic effect of CP in young and adult rats. This effect could not be enhanced by a second administration of vitamin E. The simultaneous administration of vitamin E and C 12 h prior to CP intensified the protective effect of a single administration of vitamin E in 10- and 55-day-old rats without influencing the concentration of platinum in renal tissue.

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The nephrotoxicity of three platinum (CPL, KP734, KP735) and three ruthenium coordination complexes (KP418, KP692, KP1019) was tested in rats in comparison to cisplatin (CP). Renal functional changes (excretion of water, protein, p‐aminohippurate (PAH) and osmolytes) were not observed after the administration of 10% of the LD50 of the compounds given twice a week for up to 5 weeks. After a relatively high single dose of the substances (50% of the LD50), signs of nephrotoxicity on the day of maximal renal damage decreased in the following order: CP, KP418, CPL, KP734, KP735, KP692 and KP1019. In comparison to CP, proteinuria was significantly lower after the administration of any of the compounds, especially KP692 and KP1019. Neither renal lipid peroxidation (TBARS) nor glutathion status (GSH, GSSG) was affected. In summary, KP735 in the group of platinum complexes and KP1019 in the ruthenium group had the lowest nephrotoxicity. Other investigators have shown that all complexes induced anti‐neoplastic activity under analogous experimental conditions. © 1998 John Wiley & Sons, Ltd.

The nephrotoxicity of three platinum (CPL, KP734, KP735) and three ruthenium coordination complexes (KP418, KP692, KP1019) was tested in rats in comparison to cisplatin (CP). Renal functional changes (excretion of water, protein, p-aminohippurate (PAH) and osmolytes) were not observed after the administration of 10% of the LD 50 of the compounds given twice a week for up to 5 weeks. After a relatively high single dose of the substances (50% of the LD 50 ), signs of nephrotoxicity on the day of maximal renal damage decreased in the following order: CP, KP418, CPL, KP734, KP735, KP692 and KP1019. In comparison to CP, proteinuria was significantly lower after the administration of any of the compounds, especially KP692 and KP1019. Neither renal lipid peroxidation (TBARS) nor glutathion status (GSH, GSSG) was affected. In summary, KP735 in the group of platinum complexes and KP1019 in the ruthenium group had the lowest nephrotoxicity. Other investigators have shown that all complexes induced anti-neoplastic activity under analogous experimental conditions.

Until now, no optimal local anaesthetic drug with long lasting effect and low toxicity has been developed. Fomocaine (CAS 17692-39-6), introduced in the German extrapharmacopoela (DAC) in 1979, is a local anaesthetic, which is largely in accordance with these aspects. Now the basic ether fomocaine, its metabolites O/Se 9 (CAS 3006-96-0), O/Se 10 (CAS 31719-76-3), O/Se 11, O/Se 12 (CAS 64264-21-7) and M5 and its chiralic derivatives O/G 3 and O/G 5 were compared with procaine (CAS 59-46-1) and characterised more in detail in rats. The metabolism of fomocaine was investigated earlier with 14C-fomocaine in rats and beagle dogs. Rac-O/G 3 and Rac-O/G 5 could be separated into the enantiomers via the diastereomeric salts. Basing on standard methods for the testing of the local anaesthetic effects (estimation of infiltration and conduction anaesthesia in rat tail, measurement of corneal anaesthesia) and using a couple of tests characterising the side effects and toxicity of local anaesthetic (paresis of the N. ischiadicus, tissue irritation, determination of the approximative i.p. LD50) it can be concluded that: a) The very good surface anaesthesia caused by fomocaine could be stated, but, as expected, concerning conduction anaesthesia, procaine is better qualified for clinical use. b) Fomocaine is much more effective in conduction and surface anaesthesia than its chiralic derivatives O/G 3 and O/G 5. c) Differences between the two enantiomers of the O/G-substances have been found, but these little discrepancies are without practical relevance. In the case of O/G 5, agonistic effects of both enantiomers could be shown. d) Fomocaine undergoes extensive biotransformation with subsequent formation of 14 metabolites. Five of them (O/Se 9-O/Se 12; M5) are N-free and do not show any pharmacological activity. e) Compared to other local anaesthetics, fomocaine is relatively non-toxic (nearly no tissue irritation, high approximative LD50), however, surprisingly the toxicity of the reference substance procaine has been found to be lower after i.p. administration instead of i.v. administration in comparison with fomocaine.