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The effects of combination hormone therapy of drospirenone (DRSP), a novel progestin with antialdosterone properties, and 17beta-estradiol (E2) on hydrochlorothiazide (HCTZ) pharmacokinetics/pharmacodynamics versus placebo were investigated in a double-blind, placebo-controlled, crossover study. Thirty-six postmenopausal women with stage 1 hypertension maintained on 25 mg of HCTZ once daily were randomized to receive either 3 mg of DRSP/1 mg of E2 or placebo once daily for 4 weeks. Plasma HCTZ, serum DRSP, E2, potassium, aldosterone, and plasma renin activity were determined at baseline and after 4 weeks. Results showed that the combination of DRSP/E2 plus 25 mg of HCTZ is safe and well tolerated in hypertensive postmenopausal women. The pharmacokinetics of HCTZ were not affected by coadministration of DRSP/E2. The geometric mean ratios and 90% confidence intervals ([HCTZ + DRSP/E2]/[HCTZ + placebo]) for HCTZ (a) area under the serum/plasma concentration-time curve from 0 to 24 hours and (b) maximum plasma concentration were 101 (90.7, 112) and 103 (92.8, 115), respectively. In the HCTZ + DRSP/E2 group, serum potassium, aldosterone, and plasma renin activity all increased in a manner marginally consistent with a beneficial antialdosterone effect, counteracting the HCTZ-induced potassium loss and lowering both systolic and diastolic blood pressure. No dose adjustment is required when DRSP/E2 is added to antihypertensive therapy with HCTZ in hypertensive postmenopausal women.

Hypoalbuminemia is a surrogate of malnutrition in patients with end-stage renal disease undergoing chronic dialysis and commonly improves with prescription of adequate nutrition and dialysis. Nevertheless, some patients remain hypoalbuminemic for poorly understood reasons. We tested the hypotheses that chronic dialysis patients who remain hypoalbuminemic despite prescription of adequate nutrition and dialysis (1) have delayed gastric emptying, and (2) that prokinetic agents will increase plasma albumin (P(alb)) levels in patients with delayed gastric emptying. We retrospectively identified 99 of 343 hemodialysis and peritoneal dialysis patients with hypoalbuminuria (P(alb) < 3.5 mg/dL) and studied those who did not (hypoalbuminemic, n =15) and did (normoalbuminemic, n = 15) increase their P(alb) levels over the subsequent 6 months and met inclusion and exclusion criteria. Gastrointestinal symptom scores determined by an administered questionnaire were not different in hypoalbuminemic and normoalbuminemic patients. Conversely, the half-time (T(1/2)) for radionuclide gastric emptying was longer in hypoalbuminemic than normoalbuminemic patients (74.5 +/- 7.4 versus 46.7 +/- 4.6 minutes; P < 0.004). Hypoalbuminemic patients were prescribed prokinetics and followed prospectively for 6 months, during which time gastric T(1/2) decreased to 53.9 +/- 3.3 minutes (P < 0.01 versus initial) and P(alb) increased from 3.1 +/- 0.2 to 3.5 +/- 0.2 mg/dL (P < 0.004). The net increase in P(alb) level correlated with the net decrease in gastric T(1/2) (r(2) = 0.4; P < 0.04) by linear regression. The data show that some persistently hypoalbuminemic chronic dialysis patients have poor gastric emptying and increase their P(alb) levels in response to prokinetic agents.