Acetylator phenotype in patients with hydralazine-induced lupoid syndrome.
The acteylator phenotype has been determined (isoniazid half-life) in 31 patients, 25 of them women, who had exhibited a lupus erythematosus-like syndrome during treatment with hydralazine. Twenty-nine patients were slow acetylators, one was rapid (probably spontaneous SLE) and one uncertain. Only two patients had been given more than 200 mg of hydralazine daily. The mean duration of therapy was 32 months at the onset of symtoms. These were not serious but rather long-standing. Our study confirms that patients who risk developing hydralazine lupus are slow acetylators, especially females, treated with more than 100 mg daily. Rapid acetylators seem to develop this side-effect rarely, if at all.
In this, the first of two Letters, we describe how a P3/P4 urea linking unit was used to greatly enhance the biochemical and replicon potency of inhibitors based upon the pyrrolidine-5,5-trans-lactam template. Compound 7b demonstrated a 100 nM IC50 in the replicon cell-based surrogate HCV assay.