Malondialdehyde (MDA) is a product of lipid peroxidation and prostaglandin biosynthesis. It is mutagenic and carcinogenic and the major adduct formed by reaction with DNA, a highly fluorescent pyrimidopurinone (M1-dG), has been detected in healthy human liver and leukocyte DNA. Analytical methods used so far for the detection of M1-dG have not been applied to a large number of individuals or variety of samples. Often, only a few microg of DNA from human tissues are available for analysis and a very sensitive assay is needed in order to detect background levels of M1-dG in very small amounts of DNA. In this paper, the development of an immunoslot blot (ISB) assay for the measurement of MI-dG in 1 microg of DNA is described. The limit of detection of the assay is 2.5 adducts per 10(8) bases. A series of human samples were analysed and levels of 5.6-9.5 (n = 8) and 3.1-64.3 (n = 42) of M1-dG per 10(8) normal bases were detected in white blood cell and gastric biopsy DNA, respectively. Results on four human samples were compared with those obtained using an HPLC/32P-post-labelling (HPLC/PPL) method previously developed and indicated a high correlation between M1-dG levels measured by the two assays. The advantages of ISB over other assays including HPLC/PPL, such as the possibility of analysing 1 microg DNA/sample and the fact that it is less time-consuming and laborious, means that it can be more easily used for routine analysis of a large number of samples in biomonitoring studies.

A strong and similar inhibition of plasma DHT was found after 1 week of treatment with the topical and tablet finasteride ormulations, albeit finasteride plasma exposure was significantly lower with the topical than with the oral product (p < 0.0001).

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Background/Aims: Absorption, biotransformation and elimination of safinamide, an enantiomeric α-aminoamide derivative developed as an add-on therapy for Parkinson's disease patients, were studied in healthy volunteers administered a single oral dose of 400 mg ¹⁴C safinamide methanesulphonate, labelled in metabolically stable positions. Methods: Pharmacokinetics of the parent compound were investigated up to 96 h, of ¹⁴C radioactivity up to 192/200 h post-dose. Results/Conclusions: Maximum concentration was achieved at 1 h (plasma, median T_max) for parent drug and at 7 and 1.5 h for plasma and whole blood ¹⁴C radioactivity, respectively. Terminal half-lives were about 22 h for unchanged safinamide and 80 h for radioactivity. Safinamide deaminated acid and the N-dealkylated acid were identified as major metabolites in urine and plasma. In urine, the β-glucuronide of the N-dealkylated acid and the monohydroxy safinamide were also characterized. In addition, the glycine conjugate of the N-dealkylated acid and 2-[4-hydroxybenzylamino]propanamide were tentatively identified as minor urinary metabolites.