Chlorthalidone 12.5 mg, Cilnidipine 10 mg Tablets

Chlorthalidone is a long-acting oral diuretic with antihypertensive activity. The diuretic effects of chlorthalidone and the benzothiadiazine (thiazide) diuretics appear to arise from similar mechanisms and the maximal effect of chlorthalidone and the thiazides appear to be similar. The site of the action appears to be the distal convoluted tubule of the nephron. Although the mechanism of action of chlorthalidone and related drugs is not wholly clear, sodium and water depletion appear to provide a basis for its antihypertensive effect.

Absorption — THALITONE (chlorthalidone USP) has been formulated with PVP (povidone polyvinylpyrrolidone), a bioavailability enhancer that provides 104% to 116% bioavailability relative to an oral solution of chlorthalidone [see Clinical Studies (14)]. THALITONE cannot be substituted with other formulations of chlorthalidone.

Distribution — In the blood, approximately 75% of the drug is bound to plasma proteins over a concentration range of 0.2 to 7.7 ug/mL.

Elimination — The mean plasma half-life of chlorthalidone is about 40 to 60 hours. It is eliminated primarily as unchanged drug in the urine.

Experimental findings in the reference describe inhibition of L-type calcium channels in vascular smooth muscle and N-type channels at sympathetic nerve terminals. These actions support vasodilation and reduced norepinephrine release.

In six healthy men taking 10 mg orally each day, mean peak times were 2.8–3.7 hours on the reported study days and steady state was reached by day 4. In vitro serum protein binding was 99.3%. Hepatic metabolism included CYP3A4 and CYP2C19; after repeated dosing, unchanged drug was not detected in urine and about 5.2% of the dose was recovered there as metabolites. These small reference studies do not define a different combination or release formulation.