• The Korean Journal of Pharmacology
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• v.22 no.2
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• pp.128-134
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• 1986

To determine the relationship between hydrochlorothiazide-induced diuretic action and cyclic nucleotides, the effects of hydrochlorothiazide (5 mg/kg, i.v.) on the renal tissue level of cyclic nucleotides and the renal adenylate cyclase and guanylate cyclase activity were investigated. Hydrochlorothiazide elecitied the maximal diuretic effect between 10 and 20 min after the injection of drug. The increased urine flow and urinary electrolytes excretion returned to the control levels 60 min after the injection of drug. 5 and 15 min after drug administration the cAMP level of renal tissue was significantly decreased, but 60 min after the cAMP level was not different from the control level. The cGMP level of renal tissue was not affected by hydrocholorothiazide. Hydrochlorothiazide $(5\;{\times};10^{-4}\;M)$ inhibited the renal adenylate cyclase but not affected the renal guanylate cyclase. These results suggest that cAMP may be involved in the renal action mechanism of hydrochlorothiazide and the involvement of cGMP is uncertain.

• YAKHAK HOEJI
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• v.50 no.5
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• pp.301-307
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• 2006

A simple and sensitive high-performance liquid chromatographic method for quantitation of hydrochlorothiazide in human plasma was developed and bioavailability parameters of hydrochlorothiazide were assessed in Korean healthy male volunteers. Caffeine was used as an internal standard. Hydrochlorothiazide and internal standard in plasma sample were extracted using tert-butylmethylether (TBME). A centrifuged upper layer was then evaporated and reconstituted with mobile phase of acetonitrile-25 mM phosphate buffer (20/80, pH 2.5). The reconstituted samples were injected into a Luna C18 column $(250{\times}4.6\;mm,\;5{\mu}m)$ at a flow-rate of 1.0 ml/min. The wavelength was set at 230 nm and no endogenous substances were found to interfere, A linear relationship for hydrochlorothiazide was found in the range of $10{\sim}300\;ng/ml$. The lower limit of quantitation (LLOQ) was 10 ng/ml with acceptable precision and accuracy. Assayed in plasma, the intra- and inter-day validation for all coefficients of variation (R.S.D.%) were found less than 15%. Main pharmacokinetic parameters of 50mg of hydrochlorothiazide were revealed as follows: $AUC_t\;1761{\pm}509.0\;ng{\cdot} hr\;ml,\;C_{max}\;296.5{\pm}95.5\;ng/ml,\;T_{max}\;1.94{\pm}0.85hr,\;K_{el}\;0.12{\pm}0.04\;hr^{-1}\;and T_{12}\;6.81{\pm}2.92\;hr.\;C_{max}\;and\;T_{max}$ were in accordance with the values $(270{\sim}350\;ng/ml\;and\;1.9{\sim}2.7\;hr)$ of Caucasian.

• Journal of Pharmaceutical Investigation
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• v.40 no.3
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• pp.167-173
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• 2010

Repeated oral administration of hydrochlorothiazide, a loop diuretic, due to transient high blood levels, may cause adverse effects such as gastric disturbance, nausea, high blood sugar, and hyper lipidemia. Transdermal administration could avoid some of these systemic side effects and gastric disorders. We have developed a matrix using ethylene-vinyl acetate (EVA), a heat-processible and flexible material, for transdermal delivery of hydrochlorothiazide. Drug solubility was highest at 40% PEG-400 volume fraction. Drug release increased as concentration increased with a linear relationship between the release rate and the square root of loading dose. Increasing temperature increased drug release from the EVA matrix. The activation energy, measured from the slope of log P versus 1000/T, was 11.9 kcal/mol for a 2.5% loading dose from EVA matrix. Diethyl phthalate had the highest plasticizing effects on the release of hydrochlorothiazide. To increase the skin permeation of hydrochlorothiazide from the EVA matrix, enhancers such as the saturated fatty acids, the unsaturated fatty acids, and the non-ionic surfactants were added to the EVA matrix, and skin permeation was evaluated using a modified Keshary-Chien diffusion cell fitted with intact excised rat skin. Polyoxyethylene 23-lauryl ether showed the highest enhancing effects. In conclusion, transdermal delivery of hydrochlorothiazide could be improved from an EVA matrix containing plasticizer and permeation enhancer.

• Journal of Pharmaceutical Investigation
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• v.18 no.1
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• pp.1-3
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• 1988

Effect of hydrochlorothiazide on serum potassium level was studied in the hypokalemia-induced rats by the oral administration of glycyrrhiza extract (GE) for 4 weeks. According to the concentration of GE, serum potassium levels were found to be $5.8{\pm}0.2,\;5.4{\pm}0.2\;and\;5.5{\pm}0.2\;mM/l$ after oral administration of 0.1, 0.2 and 0.5% GE solutions for 4 weeks, respectively, comparing $6.4{\pm}0.2\;mM/l$ in normal rats. The i.p. administration of hydrochlorothiazide (100mg/kg) showed no significant difference $(5.1{\pm}0.3-5.2{\pm}0.3\;mM/l)$ in the decrease of serum potassium levels between these hypokalemia-induced rats and normal rats, regardless of the concentration of pretreated GE solutions. Therefore it was considered that the administration of hydrochlorothiazide did not worsen the hypokalemia induced by the long term administration of GE in rats.

• The Journal of Korean Medicine
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• v.15 no.2 s.28
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• pp.198-211
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• 1994

After giuing some anti-high blood pressure medicine of boiled-compressed fluid and 5-Kinds factors(Hydralazine, Verapamil, Clonidine, Furosemide and Hydrochlorothiazide with Kangsimsan to animals in single or together. I got the following conclusion in comparing blood-pressure and pulse of circulating system with urinating operation. 1. By joint-use of Kangsimsan and Hydralazine. it was found out that the effect of blood-pressure lowering continues longer in together-use than in single. And I coule see that the number of pulse increased. 2. By joint-use of Kangsimsan and Verapamil. the blood-pressure lowering operation was kept better in together-use than in single. the number of pulse was not affected any. 3. By joint-use of Kangsimsan and Clonidine the blood-pressure lowering operation was not found out any concrete result. 4. By joint-use of Kangsimsan and Furosemide. the Remarkble effect of Urinization was recognized to be much better in joint-use than in single. 5. By joint-use of Kangsimsan and Hydrochlorothiazide. the suppressing effect of urinization was recognized to be much better in joint-use than in single. Therefore in consideration of the above study and observation. when the joint-use of Kangsimsan and the blood-pressure lowering medicine. Hydralazine and Verapamil. the period of blood-pressure lowering was kept and I can conclude that in case of joint-use of Furosemide, a kind of good urinization. the effect of urinization by Furosemide is increased, but that of Hydrochlorothiazide is disturbed.

• Archives of Pharmacal Research
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• v.7 no.1
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• pp.47-52
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• 1984

Four polymorphic forms (I, II, III and IV) of hydrochlorothiazide have been characterized on the basis of x-ray diffractometry and differential thermal analysis. Form I was obtained by crystallization from N, N-dimethylformamide and Form II was crystallized from hot methanol. Form III was precipitated from sodium hydroxide aqueous solution by treatment with hydrochloric acid and Form IV was crystallized from 50% methanol. The metastable form I was a most stable form among four polymorphs, which was stable more than ten months at room temperature. The thermodynamic parameters such as heat of solution, enthalpy, entropy, free energy difference and transition temperature were determined by the measurement of intrinsic dissolution rate. The transition temperature and the heat of transition between the metastable Form I an Form II were determined to be $299.15^{\circ}$K and 5.03 Kcal/mole, respectively and free energy difference ($\delta$ F) was 302. 13 cal/mole. Diuretic action of these four polymorphic forms was also evaluated by monitoring the difference in urinary excretion of sodium, potassium and magnesium in rats.

• YAKHAK HOEJI
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• v.27 no.2
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• pp.149-154
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• 1983

The effect of hydrochlorothiazide on the pharmacokinetics of carteolol in rabbits was studied. Animals were divided into two groups (group I and group II). Group I received carteolol (12mg/kg) and group II received carteolol (12mg/kg) with hydrochlorothiazide (20mg/kg) orally. The carteolol concentration in serum was measured by spectrofluorometric method and its pharmacokinetic parameter values were calculated. The serum concentration of carteolol in group II was significantly increased when compared with those in group I at 10min (p<0.01), and at 30min (p<0.05) after p. o. administration. In addition, the absorption rate constant of carteolol in group II was slightly increased and Tmax of carteolol in group II was significantly shortened (p<0.05) and Cmax of carteolol in group II was significantly increased (p<0.02) when compared with those in group I. But elimination rate constant and biological half-life of carteolol were similar in both groups.

• Clinical and Experimental Pediatrics
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• v.45 no.3
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• pp.413-417
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• 2002

Gitelman's syndrome is an autosomal recessive disorder characterized by hypokalemic metabolic alkalosis, hypomagnesemia, and hypocalciuria that has recently been reported to be linked to thiazide- sensitive Na-Cl cotransporter gene mutation. In this study, we performed renal clearance studies to differentiate Gitelman's from Bartter's syndrome and to confirm the diagnosis in two patients clinically diagnosed with Gitelman's syndrome. Each patient was hydrated by 20 mL/kg body weight of oral water within 30 minutes, which was followed by intravenous half saline. When urinary flow reached 10 mL/min, samples of urine and serum were obtained to calculate the osmolar clearance, free water clearance, chloride clearance, and distal fractional chloride reabsorption. Subsequently, furosemide or hydrochlorothiazide was administered. Samples were collected and the same parameters were calculated. In our patients, chloride clearance was increased more than 10 times after furosemide administration(2.1 : 25.7 and 2.2 : 27.4 mL/min/100 mL GFR), but not increased after hydrochlorothiazide treatment(2.1 : 1.6 and 2.2 : 2.6 mL/min/100 mL GFR). And the distal fractional chloride reabsorption was significantly decreased by furosemide injection (73% : 15% and 75% : 4.6%), whereas hydrochlorothiazide had no effect on it(73% : 63% and 75% : 78%). These findings indicate that our patients have a defect in thiazide-sensitive Na-Cl cotransporter in the distal tubule, which is compatible with the pathophysiology of Gitelman's syndrome.

• 대한임상약리학회:학술대회논문집
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• 1998.12a
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• pp.38-38
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• 1998

• Clinical and Experimental Pediatrics
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• v.48 no.6
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• pp.669-674
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• 2005

Nephrogenic diabetes insipidus (NDI) is a disorder in which the secretion of antidiuretic hormone is normal, but the response of the renal collecting tubules to vasopressin is impaired. Compared with acquired NDI (a-NDI), which is secondary to chronic bilateral incomplete urinary tract obstruction with hydronephrosis, congenital NDI (c-NDI) is a very rare heritable disorder that usually follows the X- linked recessive pattern. Clinical symptoms of c-NDI can be non specific, and often the disease ultimately results in failure to thrive, or mental retardation. Recently, the diagnosis can be confirmed by direct sequencing analysis of the peripheral blood specimens. The long-term results of treatment for c-NDI are not satisfactory. Reports on the follow up of c-NDI cases are rare and there is no report on the cases treated with combinations of three drugs. We report herein a case of severe c-NDI in an 8 year-old-boy with a severely dysconfigurated urinary tract system. The patient and his mother showed a frameshift mutation on the AVPR2 gene on chromosome Xq28:.847_851delTGCTG (p.C283fsX90). The patient showed normal growth and development by treatment with combinations of hydrochlorothiazide ($65mg/m^2$), amiloride (0.3 mg/kg/d) and indomethacin ($100mg/m^2$), yet after five years he needed adjuvant cystostomy to relieve him from the residual symptoms of urgency with polyuria.