Identification of the reactive metabolites of fenclozic acid in bile duct cannulated rats.

Fenclozic acid (Myalex) was developed by ICI pharmaceuticals in the 1960s for the treatment of rheumatoid arthritis and was a promising compound with a good preclinical safety profile and efficacy. While it did not show adverse hepatic effects in preclinical animal tests or initial studies in man [ Chalmers et al. Ann.

The stability of amitriptyline N-oxide and clozapine N-oxide on treated and untreated dry blood spot cards.

Procedures for drug monitoring based on Dried Blood Spot (DBS) sampling are gaining acceptance for an increasing number of clinical and preclinical applications, where ease of use, small sample requirement, and improved sample stability have been shown to offer advantages over blood tube sampling. However, to-date, the vast majority of this work has described the analysis of well characterized drugs. Using amitriptyline, clozapine, and their potentially labile N-oxide metabolites as model compounds, we consider the merits of using DBS for discovery pharmacokinetic (PK) studies where the metabolic fate of test compounds are often unknown.