Racial differences in response to acute dosing with hydrochlorothiazide.
Blacks demonstrate a higher response rate to diuretic therapy for hypertension than do whites. This study examined the pharmacokinetic (PK), pharmacodynamic, and neurohumoral effects of hydrochlorothiazide (HCTZ) administration in a matched group of 9 black and 9 white hypertensive patients (mean +/- SD for black and white). After a 4-week washout period and 7-day control diet, subjects received a single dose of HCTZ (25 mg at 8 AM) with serial blood and urine collections for 36 hours. After HCTZ sodium excretion increased comparably in both groups (blacks: 122 +/- 42 pre to 265 +/- 49 mEq/24 hours post; whites: 117 +/- 29 pre to 255 beta 39 mEq/24 hrs post). Potassium excretion tended to be higher at baseline and was significantly higher following HCTZ in whites (blacks: 45 beta 20 pre to 66 beta 13 mEq at 24 hours post; blacks: 57 +/- 9 pre to 86 +/- 14 mEq at 24 hours post) with most of the post-dosing difference being observed in the hours 0 to 12 after HCTZ. There were no between group PK differences for urinary HCTZ. Aldosterone excretion followed a normal circadian pattern in the whites but did not show this pattern in the blacks. Aldosterone excretion (0 to 12 hours) was generally lower post-dosing in blacks. In conclusion, whereas the PK and single-dose natriuretic response for HCTZ were not racially distinct, potassium excretion was notably less in blacks. Aldosterone excretion was also lower in blacks and without its normal circadian pattern which may, in part, explain their altered potassium excretion pattern.
Ripley
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E
Division of Nephrology, Medical College of Virginia Commonwealth University, Richmond, USA. bripley@hsc.vcu.edu
King
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K
Sica
D A
DA
D000328:Adult; D000450:Aldosterone / Q000652:urine; D044383:Black People; D001794:Blood Pressure / Q000187:drug effects; D002940:Circadian Rhythm; D004232:Diuretics; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy* / Q000208:ethnology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011188:Potassium / Q000097:blood / Q000652:urine; D012964:Sodium / Q000097:blood / Q000652:urine; D049993:Sodium Chloride Symporter Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome; D044465:White People
D004232:Diuretics; D049993:Sodium Chloride Symporter Inhibitors; D006852:Hydrochlorothiazide; D000450:Aldosterone; D012964:Sodium; D011188:Potassium