Variability of plasma hydralazine concentrations in male hypertensive patients.

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Ludden TM, McNay JL Jr, Shepherd AM, Lin MS

Variability of plasma hydralazine concentrations in male hypertensive patients.

Arthritis Rheum. 1981 Aug;24(8):987-93. doi: 10.1002/art.1780240802.

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7284051 [ View in PubMed
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Abstract

The efficacy and toxicity of hydralazine differ widely among individual patients, possibly because of different sensitivities to drug effect or as a reflection of pharmacokinetic differences. Therefore, the variability in plasma hydralazine concentrations after single intravenous and single and multiple oral doses was studied in 9 male hypertensive patients. After an intravenous dose of 0.3 mg/kg the area under the plasma concentration time curve (AUC) varied over less than a twofold range 17.5-29.5 muM-minute. However, after a single oral dose, 1 mg/kg, and after at least the fifth dose of a regimen consisting of 1 mg/kg given every 12 hours, there were much wider variations in AUC values: 4.0-30.4 and 3.2-38.5 muM-minute, respectively. Similar ranges in peak hydralazine concentration, Cp, were also noted, 0.12-1.31 muM after single oral dose and 0.10-1.39 muM after the multiple dose regimen. A significant portion of the observed interpatient variability could be explained by differences in acetylation ability. The AUC and Cp values for both the single and multiple oral doses were significantly lower (P less than 0.001) in rapid than in slow acetylators. Therefore, determining the acetylation ability of patients requiring hydralazine may help to optimize therapeutic benefit and minimize toxicity.

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