Studies on hydralazine. II. Elimination rate and steady-state concentration in patients with impaired renal function

Following a single 50 mg dose of hydralazine (Apresoline) in 13 patients with impaired renal function, a decrease in glomerular filtration rate (GFR) was correlated with an increase in serum half-life (T1/2) of the drug (r=-0.69; p less than 0.01). The T1/2 was 15.8 h in one patient with a GFR of 16 ml-min-1, as compared to a T1/2 of 1.7-3.0 h found previously in 16 healthy volunteers. In 49 patients on long-term antihypertensive treatment with hydralazine, the ratio between the minimum steady-state drug concentration and the daily dose of hydralazine (Cminss : Dose) increased as the GFR decreased. This accumulation of the drug was particularly evident in patients with a GFR less than 30 ml-min-1 (r=-0.63; p less than 0.01; n=19). As renal excretion of unchanged hydralazine is generally regarded as unimportant, the slower elimination rate in chronic renal failure was probably caused by a slower rate of metabolic conversion. It was found, however, that the renal excretion of hydralazine could easily have been underestimated, as only 12.7% of an initial hydralazine concentration of 200 ng-ml-1 in urine could be recovered after storage of the samples at room temperature for 24 h.