Microzide
Simultaneous determination of hydrochlorothiazide and amiloride hydrochloride by ratio spectra derivative spectrophotometry and high-performance liquid chromatography.

Kartal M, Erk N.

Department of Pharmacognosy, Faculty of Pharmacy, University of Ankara, Turkey.

Rapid, precise, accurate and specific ratio spectra derivative spectrophotometry and high-performance liquid chromatographic procedures were described for the simultaneous determination of hydrochlorothiazide and amiloride hydrochloride in combined pharmaceutical dosage forms. For the first method, ratio spectra derivative spectrophotometry, the signals were measured at 285.7 nm for hydrochlorothiazide and at 302.5 nm for amiloride hydrochloride in the mixture, in the first derivative of the ratio spectra. The second method is based on high-performance liquid chromatography (HPLC) on LiChrosorb RP-C18 column (5 microm, 20 cm x 4.6 mm) using 0.025 M orthophosphoric acid (adjusted to pH 3.0 with triethylamine (TEA)), acetonitrile (84:16 v/v) as a mobile phase at a flow rate of 1.2 ml/min(-1). Detection was carried out using a UV detector at 278.0 nm. Commercial sugar-coated and laboratory-prepared mixtures containing both drugs in different proportions were assayed using the developed methods.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10704113&dopt=Abstract hydrochlorothiazide Microzide



Microzide
Vasodilatory effect of diuretics is dependent on inhibition of vascular smooth muscle carbonic anhydrase by a direct mechanism of action.

Puscas I, Coltau M, Baican M, Domuta G, Hecht A.

Romanian Academy of Medical Sciences, Simleu Silvaniei Center for Research and Medical Care, Salaj, Romania. ccam teli.netcompsj.ro

Five years ago, our in vitro and in vivo studies demonstrated for the first time that diuretic agents such as furosemide, hydrochlorothiazide, amiloride, triamterene and spironolactone inhibit carbonic anhydrase (CA) I, II and renal CA IV by a direct mechanism of action. In this paper we investigate the relationship between diuretics and CA I in the vasodilatory mechanism. Both in vitro (on purified CA I, erythrocyte CA I and smooth muscle CA I) and in vivo (in human and rabbits) we studied the effect of acetazolamide, hydrochlorothiazide, indapamide, furosemide, amiloride and triamterene on purified CA I, on human erythrocyte CA I, as well as on CA I isolated from vascular smooth muscle. Our results demonstrate that in vitro all diuretics inhibit CA I by a direct mechanism of action. Inhibition reached 100% with acetazolamide, 45% with hydrochlorothiazide, 82% with indapamide, 85% with furosemide, 68% with amiloride and 58% with triamterene. In vivo, similar inhibition of erythrocyte and smooth muscle CA I was obtained, being parallel with a reduction in arterial blood pressure values. Our data show that in addition to their already known mechanisms, diuretics also inhibit CA in vascular smooth muscle. Our results suggest that this mechanism is achieved by means of pH changes induced by CA I inhibition.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10713865&dopt=Abstract hydrochlorothiazide Microzide



Microzide
Statistical optimization of a reversed-phase liquid chromatographic method for the analysis of amiloride and hydrochlorothiazide in tablets.

Zecevic M, Zivanovic LJ, Agatonovic-Kustrin S, Ivanovic D, Maksimovic M.

Institute of Pharmaceutical Chemistry and Drug Analysis, Faculty of Pharmacy, Belgrade, Serbia.

A method has been developed for the separation of hydrochlorothiazide and amiloride by high-performance liquid chromatographic (HPLC) method on a C18 column with detection at 280 nm. The optimal conditions of separation were determined with the aid of 'window diagram' technique of Laub and Purnell. The effect of simultaneously varying the pH, proportion aqueous acetic acid and methanol in the mobile phase were studied to optimize the separation. A response surface diagram was used to optimize the experimental conditions for the separation. The mobile phase composition that provides an acceptable resolution hydrochlorothiazide and amiloride in a short elution time is water:methanol (60:40) and pH 3.2 (pH adjusted to 3.2 with CH3COOH). A method is applied for the quantitative analysis of Moduretic tablets (Merck Sharp & Dokme International). The powdered tablets are extracted with methanol, containing caffeine as the internal standard, and assayed by comparison of peak areas after liquid chromatography.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10727117&dopt=Abstract hydrochlorothiazide Microzide



Microzide
[Antihypertensive efficacy of monotherapy in increasing doses versus therapy associated in low doses]

[Article in Spanish]

Fasce E, Wagemann H.

Facultad de Medicina, Universidad de Concepcion, Chile.

BACKGROUND: When hypertension treatment does not achieve the expected reduction in blood pressure levels, experts recommended increasing the dose of the initially used drug or the addition of a new medication. AIM: To compare the efficacy of increasing doses of losartan or the addition of hydrochlorothiazide to achieve adequate blood pressure levels in patients with hypertension. PATIENTS AND METHODS: Seventy- three patients aged 64.4 +/- 5.3 years, with stage 1 or 2 essential hypertension were studied. If after four weeks of treatment with losartan 50 mg od, blood pressure levels were still high, the dose was increased to 100 mg od. After four weeks with this new schedule, the treatment was switched to losartan 50 mg and hydrochlorothiazide 12.5 mg for another four weeks. RESULTS: Thirty- seven patients normalized blood pressure with losartan 50 mg od. Of the 36 patients that did not respond, 69% achieved a normal blood pressure with losartan 100 mg od and 81% did so with the combination of losartan and hydrochlorothiazide. Combination therapy resulted in a better blood pressure lowering than monotherapy (33.2 +/- 3.2 and 29.5 +/- 3.4 mm Hg for systolic blood pressure respectively, 16.4 +/- 3.2 and 13.2 +/- 3.4 mm Hg for diastolic blood pressure, p < 0.05). No changes in blood glucose, total and HDL cholesterol, triglycerides, urea nitrogen and uric acid were observed with the combination therapy. CONCLUSIONS: In this group of patients, combination therapy achieved better blood pressure levels than monotherapy in high doses.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10752251&dopt=Abstract hydrochlorothiazide Microzide



Microzide
Increased phototoxicity of hydrochlorothiazide by photodegradation.

Han KD, Bark KM, Heo EP, Lee JK, Kang JS, Kim TH.

Department of Dermatology, College of Medicine, Gyeongsang National University, Chinju, Kyungnam, Republic of Korea.

The photodegradation products of hydrochlorothiazide produced by ultraviolet (UV) radiation were investigated for their phototoxicity utilizing the photohemolysis and Candida albicans tests. Hydrochlorothiazide was irradiated for 30, 60, 90 and 120 min with a 250 W xenon arc lamp using a WG295 cut-off filter. Irradiation of hydrochlorothiazide resulted in the gradual decrease of all three absorption bands (225, 270 and 320 nm), the blue shift of the 225 nm band, and the appearance of a new band around 290 nm. Since previous results demonstrated that photosubstitution of chloride could occur, the main product of this photolysis most likely is ethoxyhydrochlorothiazide. The photohemolysis test revealed a significant increase in photohemolysis observed in the photodegradation products produced after 60, 90 and 120 min of UV irradiation. This increase in hemolysis value directly correlated with the UV-irradiation time. However, there was no significant phototoxic killing of yeast in the Candida albicans test. This suggests photodegradation products of hydrochlorothiazide may play an important role in phototoxicity by acting on the cell membrane, but not on DNA. Considering the high in vitro phototoxicity observed in bendroflumethiazide and the data presented here, substitution of chloride seems to be responsible for the increased phototoxicity of hydrochlorothiazide.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10885441&dopt=Abstract hydrochlorothiazide Microzide