Effect of powder substrate on the dissolution properties of methyclothiazide liquisolid compacts.

The effects of powder substrate composition on the in vitro release properties of methyclothiazide liquisolid compacts were evaluated. The dissolution patterns of this water-insoluble drug formulated in liquisolid tablets were also compared to those of commercial products. According to the new liquisolid technique, liquid medications such as solutions or suspensions of water-insoluble drugs in suitable nonvolatile liquid vehicles can be converted into acceptably flowing and readily compressible powders by a simple admixture with certain powder substrates, which are selected powders referred to as the carrier and coating materials. Enhanced release profiles may be exhibited by such systems due to the increased wetting properties and surface of drug available for dissolution. Liquisolid tablets of methyclothiazide containing a 5% w/w drug solution in polyethylene glycol 400 were prepared using powder substrates of different excipient ratios. The release rates of such products were assessed using the USP dissolution test and were compared to those of their commercial counterparts. It was observed that maximum drug dissolution rates can be exhibited by systems that have powder substrates with optimum carrier-to-coating ratios. In addition, liquisolid tablets displayed significantly enhanced dissolution profiles compared to those of marketed products.

Antihypertensive and metabolic effects of concomitant administration of terazosin and methyclothiazide for the treatment of essential hypertension.

The efficacy and safety of once-daily 2.5- or 5.0-mg methyclothiazide (MCTZ) added to once-daily 5.0-mg terazosin (TRZ) versus 5.0-mg TRZ alone was evaluated in this double-blind, multicenter study. All patients received TRZ during a 6-week titration period. Hypertensive patients (222) (mean blood pressure of 159/104 mm Hg) were randomized to one of three treatment groups: TRZ alone (N = 76); TRZ+MCTZ-2.5 mg (N = 74); and TRZ+MCTZ-5.0 mg (N = 72) for the 8-week double-blind period. Changes in the supine and standing SBP/DBP from preTRZ period were: TRZ alone (-4.8/-8.1 and -2.6/-6.1 mm Hg); TRZ+MCTZ-2.5 mg (-17.3/-12.4 and -16.0/-11.2 mm Hg); and TRZ+MCTZ-5.0 mg (-20.6/-14.4 and -23.3/-14.6 mm Hg). Blood pressure changes in the combination groups were significantly greater than those in the TRZ alone group. However, there were no statistically significant differences between the TRZ+MCTZ-2.5-mg and TRZ+MCTZ-5.0-mg groups. The combination of TRZ and MCTZ tends to mitigate the adverse effects on serum glucose, uric, potassium and lipids usually associated with thiazide diuretics. Thus, combination treatment that begins with TRZ and adds MCTZ is effective in lowering blood pressure without any significant adverse metabolic effects.

The effects of terazosin and methyclothiazide on blood pressure and serum lipids.

This study compared the antihypertensive efficacy and the effects on serum lipids of terazosin, a new selective alpha 1-adrenergic antagonist, of methyclothiazide (MCTZ), and of the two drugs used as combination therapy. Adult patients with supine diastolic blood pressure ranging from 95 to 120 mm Hg were eligible to enter this double-blind, randomized, parallel-group study. Analyses of the blood pressure data from the 194 evaluable patients revealed that all three treatments produced significant (p less than 0.001) reductions in supine and standing systolic and diastolic blood pressures from baseline values. Moreover, combination therapy resulted in significantly greater mean blood pressure reductions than were observed with either drug used as monotherapy. In the group receiving terazosin monotherapy, the total serum cholesterol level, low-density lipoprotein plus very-low-density lipoprotein cholesterol fraction, and triglyceride level fell significantly (median changes of 3.7%, 5.0%, and 16.3%, respectively, p less than 0.05). However, in the group receiving MCTZ monotherapy, the total serum cholesterol level, low-density lipoprotein plus very-low-density lipoprotein cholesterol fraction, and triglyceride level increased significantly (4.7%, 7.1%, and 12.5%, respectively, p less than 0.001). In contrast, no significant changes from baseline values were observed for any lipid variable in the group receiving terazosin/MCTZ combination therapy. We conclude that terazosin is effective antihypertensive therapy that has a potentially beneficial effect on the serum lipid profile when used as monotherapy and that it counteracts the negative impact of MCTZ monotherapy on the serum lipid profile when used concurrently with this thiazide diuretic.

Influence of dosage and duration of therapy on the rate of response to methyclothiazide in essential hypertension.

One hundred twenty patients with essential hypertension were studied to determine whether patients who had not responded to the usual dose of a thiazide (methyclothiazide, 5 mg daily during a six-week drug trial) would respond to a higher dose (10 mg daily). The 14-week study was divided into three periods: (1) a two-week placebo period; (2) a six-week single-blind trial; and (3) a six-week period for double-blind dose comparison. Among the 77.3 percent of patients who responded to the drug, diastolic blood pressure was reduced to 90 mm Hg or lower. Two types of thiazide responders were identified-early and late. The early responders (50 percent of study patients), showed a significant reduction in diastolic blood pressure within four weeks; the late responders (27.3 percent) showed a modest reduction in diastolic blood pressure during the first four weeks of therapy, followed by a plateau lasting about two weeks, then a further significant reduction in blood pressure during the ensuing six weeks. Hypokalemia was more common in early responders. There were no significant differences in late response among patients who continued on the usual dose of methyclothiazide compared to those whose dosage was doubled, suggesting that the late response was not due to increasing the dose of the drug.