The effects of losartan and losartan/hydrochlorothiazide fixed combination on zinc and magnesium metabolism in patients with hypertension

Drug combinations with thiazides (TZD) are common in the treatment of hypertension. We have previously shown that treatment with ACE inhibitors increased urinary Zinc (Zn) excretion, while TZD enhance urinary Zn and magnesium (Mg) losses. The effects of angiotensin receptor blockers on Zn and Mg metabolism are unknown. Sixteen Caucasian hypertensives (10 men, age 51±3 years,(SEM), body mass index 31±2 kg/m2), received losartan (LOS) 50mg (Ocsaar, MSD) for 4 weeks and LOS 50mg+hydrochlorothiazide (HCT) 12.5mg (Ocsaar plus, MSD) for the next 4 weeks. Serum, peripheral blood mononuclears (PBMC) and 24-hour urinary Zn and Mg concentrations were determined at baseline, after LOS and after LOS+HCT treatments. LOS treatment significantly increased urinary Zn excretion (from 0.24±0.07 mcg/mg creatinine to 0.43±0.08 mcg/mg creatinine, p=0.01), and was associated with a significant decrease in PBMC Zn levels (from 13.8±0.8 mcg/mg protein to 12.4±0.8 mcg/mg protein, p=0.01). LOS+HCT further increased urinary Zn excretion (from 0.43±0.08 mcg/mg creatinine after LOS to 0.74±0.2 mcg/mg creatinine after LOS+HCT, p=0.04), but had no effect on PBMC Zn concentrations. Serum Zn concentrations remained unchanged after both treatments. Serum and PBMC Mg concentrations, and urinary excretion of Mg remained unchanged too. Treatment with LOS, induces increased urinary Zn excretion and Zn depletion in hypertensive patients. HCT has an additive effect. LOS and LOS+HCT had no effect on Mg metabolism. Clinical Pharmacology & Therapeutics (2004) 75, P12–P12; doi: 10.1016/j.clpt.2003.11.046