• 대한약리학회지
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• 제22권2호
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• pp.128-134
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• 1986

hydrochlorothiazide의 이뇨작용과 cyclic nucleotides와의 관계를 알아보기 위해 신조직내cyclic nucleotides 함량과 adenylate cyclase 및 guanylate cyclase 활성에 대한 hydrochlorothiazide의 영향을 관찰하였다. hydrochlorothiazide를 정맥내 투여시 약물투여 후 10분과 20분 사이에서 이뇨작용이 가장 강하게 나타났으며 60분 경과시는 이뇨작용이 소실되었다. 신조직 내 CAMP 함량은 약물투여 후 5분과 15분에 유의하게 감소되었으며 60분 경과시는 대조군과 차이가 없었다. 신조직내 cGMP 함량은 hydrochlorothiazide에 의해 영향받지 않았다. 신조직의 adenylate cyclase는 hydrochlorothiazide에 의해 활성이 억제되었으며 guanylate cyclase는 영향받지 않았다. 이상의 결과는 hydrochlorothiazide의 이뇨작용에 cAMP가 어떤 관련성을 가질 것을 시사하며 cGMP는 관련성이 없는 것으로 사료된다.

• 약학회지
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• 제50권5호
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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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• 제40권3호
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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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• 제18권1호
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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.

• 대한한의학회지
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• 제15권2호
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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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• 제7권1호
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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.

• 약학회지
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• 제27권2호
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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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• 제45권3호
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• pp.413-417
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• 2002

증후군은 원위세뇨관 Na-Cl 공동운반체 유전자 이상으로 발생하는 상염색체 열성 유전질환으로, 저칼륨혈증, 저마그네슘혈증, 대사성 알칼리증, 그리고 저칼슘뇨증 등의 임상적 특징을 보이는 질환이다. 저자들은 Bartter 증후군과의 감별진단과 Gitelman 증후군의 확진을 위해 임상적으로 Gitelman 증후군이 의심되는 두명의 환아에서 신장청소검사를 시행하였다. 각각의 환아는 밤사이 금식을 시킨 후 물 20 mL/kg를 30분에 걸쳐 경구 투여하였고, 곧 이어 half saline을 정맥을 통해 분당 5 mL의 속도로 투여하기 시작하였다. 소변양이 분당 10 mL에 도달했을 때의 검체로 삼투질제거율, 유리수분제거율, 염소제거율, 원위분획염소재흡수율을 계산하였다. 그 후에 첫째 날은 furosemide, 둘째 날은 hydrochlorothiazide를 각각 투여하고 나서 같은 신장청소검사를 시행하였다. 이뇨제를 투여하기 전 원위분획염소재흡수율은 각각 73%, 75%로 정상범위에서 약간 감소되어 있었다. furosemide를 투여한 후 삼투질제거율은 증가하였고 유리수분제거율은 감소하였다. 염소제거율은 10배 이상 증가하였으며, 원위분획염소재흡수율은 현저한 감소를 보였다. Thiazide를 투여한 후에는 위와 같은 청소율의 변화들을 관찰할 수 없었다. 신장청소 검사의 소견은 본 연구의 환아들이 헨레의 고리 상행각의 이상보다는 원위세뇨관 Na-Cl 공동운반체의 이상이 있음을 보여주고 있어 Gitelman 증후군의 병태 생리와 잘 일치한다고 사료된다.

• 대한임상약리학회:학술대회논문집
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• 대한임상약리학회 1998년도 제7차 추계학술대회 및 정기총회
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• pp.38-38
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• 1998

• Clinical and Experimental Pediatrics
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• 제48권6호
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• pp.669-674
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• 2005

신성 요붕증은 항이뇨호르몬의 정상적 분비에도 불구하고, 신장의 집합관의 항이뇨호르몬에 대한 반응이 저하되어 요농축능에 이상이 초래되는 질환이다. 특히 선천성 신성 요붕증은 대게 반성 열성 유전 양식을 따르는 유전 질환으로 매우 드물어 소아에서는 간헐적 보고만 있어 왔다. 어린 소아에서는 증상이 비특이적일 수 있고, 임상적 진단도 쉽지 않은데, 최근에는 항이뇨 호르몬 수용체 유전자의 돌연변이들이 확인되어 유전자 검사로 확진이 가능하게 되었다. 기존의 보고들은 선천성 신성 요붕증이 진단된 환아들에 대한 이뇨제나 비스테로이드성 항염증제 등을 포함한 치료가 이루어진 증례보고이었으나 이들의 치료 후 장기적 추적 결과 보고가 극히 드물며, 이들 약제에 의한 치료 효과는 낮은 것으로 알려져 있다. 저자들은 극심한 이뇨로 인한 이차적 요로기관의 변형이 초래되었던 8세 소아에서 환아와 엄마의 말초 혈액 유전자 분석 검사상 Xq28 염색체 부위의 AVPR2 유전자의 돌연변이가 확인되었고 hydrochlorothiazide, indomethacin 및 amiloride 병합 치료 후 배뇨량은 하루 12리터에서 4리터로 감소하였고, 성장 발육도 정상이었으나 더 이상의 호전이 없고 일상 생활에 불편함이 지속되어 보조적 방광루 형성술을 시행받은 후, 증상 호전 및 심리적 안정을 얻었던 심한 선천성 신성 요붕증 1례의 5년간의 추적 관찰 결과를 보고하는 바이다.