Accumulation of pinacidil N-oxide during chronic treatment with pinacidil

The effects of acute and chronic administration of a slow-release preparation of pinacidil have been studied in eight normotensive volunteers aged 40-57 years. Continuous administration of 20 mg b.i.d. pinacidil had no effect on serum pinacidil concentrations measured as AUC (0-9 h), but accumulation of the principal metabolite, pinacidil pyridine-N-oxide was found to occur. There were no significant changes in erect and supine blood pressure and heart rate from the pretreatment levels on days 1,15 or 29. Chronic administration of pinacidil caused a significant increase in weight over the total period of study. There were also significant changes in mean sodium (+2.38 mmol/l) and alkaline phosphatase (+15.75 iU/l) from the start to the end of pinacidil therapy but values were within the normal ranges, except for one alkaline phosphatase. There were significant changes in the following haematological parameters over the period of pinacidil therapy; leukocytes (-1.49 x 10(9)/l), haemoglobin (-0.56 g/dl), MCH (-1.1 pg), MCHC (-1.22 g/dl), platelet MCV (-0.90 fl).