RESUMO
A randomised cross-over study in 24 postmenopausal women was selected to establish bioequivalence of two tamoxifen (CAS 10540-29-1) formulations. In addition, this study compiled pharmacokinetic parameters for the current 30 mg regimen in postmenopausal women, the target population of tamoxifen therapy. Mean Cmax values of 59.1 +/- 8.9 (T) and 63.6 +/0 11.1 (R) ng/ml were attained 3.6 +/- 1.2 (T) and 3.2 +/- 1.1 (R) h after administration of 30 mg tamoxifen for the test (T) and the reference (R) formulation. The mean AUC (0-480) of tamoxifen was calculated as 3299.7 +/- 761.2 (T) and 3370.1 +/- 701.9 (R) ng x h/ml. The corresponding AUC (0-480) of the active metabolite, N-desmethyl-tamoxifen, exceeded that of the parent drug with 4359.7 +/- 830.5 (T) and 4306.3 +/- 835.2 (R) ng x h/ml, whereas maximal concentrations of the metabolite were distinctly decreased with 14.4 +/- 3.3 (T) and 14.3 +/- 2.4 (R) ng/ml. The pharmacokinetic parameters evaluated in this study are well in line with already known pharmacokinetic data generated with young male volunteers and postmenopausal patients with breast cancer. Precise analytics and an extremely long blood sampling period facilitated an accurate determination of tamoxifen's half-life in postmenopausal women with 210.1 +/- 60.8 (T) and 209.8 +/- 59.9 (R) h. Based on the extremely long half-life, the suitability of a cross-over design is discussed and recommended for further studies.
Assuntos
Antineoplásicos Hormonais/farmacocinética , Tamoxifeno/farmacocinética , Adulto , Idoso , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/sangue , Disponibilidade Biológica , Biotransformação , Estudos Cross-Over , Feminino , Meia-Vida , Humanos , Pessoa de Meia-Idade , Tamoxifeno/administração & dosagem , Tamoxifeno/análogos & derivados , Tamoxifeno/sangue , Equivalência TerapêuticaRESUMO
The isolated liver perfusion technique was used to study the effect of therapeutic doses of paracetamol on hepatic gluconeogenesis and bromosulphthalein clearance from the perfusate and biliary excretion of the dye in the rat. Six groups of rats were studied; those in the three experimental groups were given 0.02 g kg-1 paracetamol daily for ninety days. The livers of animals in the control group and in one of the experimental groups were perfused with a medium containing pyruvate. The animals in the second experimental and control group were perfused with a medium containing bromosulphthalein (10 mg/100 mL). The livers of the third experimental and control group were subjected to histological examination. The rate of glucose formation and glucose concentrations were decreased, while, lactate levels and lactate: pyruvate ratios were increased in paracetamol-treated rats. The mean concentration of bromosulphthalein in the perfusate and biliary excretion of the dye were decreased. Macro and micro vesicular fatty change was present in the livers of paracetamol-treated rats. This study demonstrates that chronic administration of therapeutic doses of paracetamol to rats adversely affects liver function, as evidenced by impaired gluconeogenesis and bromosulphthalein clearance from the perfusate, and excretion of the dye into the bile, and provides histological evidence of hepatic damage in rats.
Assuntos
Acetaminofen/farmacologia , Fígado/efeitos dos fármacos , Fígado/fisiologia , Animais , Biópsia , Gluconeogênese/efeitos dos fármacos , Fígado/citologia , Masculino , Microscopia , Modelos Biológicos , Perfusão , Ratos , Ratos Wistar , Sulfobromoftaleína/farmacocinéticaRESUMO
Administration of an initial oral dose of hydrochlorothiazide 25 mg to healthy subjects is followed by increased 24-hour urinary outputs of sodium, chloride, and potassium. On the fourth day of once-daily dosing with hydrochlorothiazide 25 mg, 24-hour natriuresis and chloriuresis are no longer augmented, but the elevation in 24-hour kaliuresis that follows the first dose remains unchanged. Twenty-four-hour urinary calcium output is consistently reduced during repeated once-daily administration of hydrochlorothiazide 25 mg. The first oral dose of the loop diuretic torasemide augments the average natriuresis and kaliuresis in the 6 hours immediately after dosing in healthy subjects, in a dose-dependent fashion, within the 2.5 to 10-mg range. These increased urinary outputs are followed by rebounds below postplacebo values between 6 and 24 hours after dosing. As a result of this biphasic response, torasemide 2.5 mg qualifies as a nondiuretic formulation (it does not elevate 24-hour natriuresis), whereas torasemide 5 and 10 mg qualify as diuretic formulations. After the seventh dose of torasemide 5 or 10 mg during a regimen of once-daily therapy, 24-hour urinary sodium and chloride outputs no longer differ from their postplacebo counterparts. Twenty-four-hour kaliuresis tends to increase in a dose-dependent fashion after the first dose of torasemide (torasemide 2.5 and 5 mg do not augment it significantly), but this tendency is no longer present after the seventh once-daily dose, when torasemide (2.5, 5, or 10 mg) does not elevate the mean 24-hour kaliuresis. Twenty-four-hour calciuresis tends to increase in a dose-dependent manner (torasemide 2.5 mg does not elevate it significantly) after the first dose of torasemide; this calciuretic effect does not change in intensity after 7 days of once-daily treatment. The time course of natriuresis over the 24 hours following the administration of any given formulation of a loop or of an early distal tubular diuretic to healthy subjects is alike after the first and after the nth once-daily dose; therefore, it constitutes a definite characteristic of any given oral formulation. In the case of torasemide, lower doses have more protracted effects on natriuresis, to the extent that the time course of natriuresis over the 24 hours after administration of torasemide 2.5 mg to healthy subjects resembles the time course after administration of hydrochlorothiazide 25 mg, rather than the time course after administration of the overtly diuretic formulation torasemide 10 mg.
Assuntos
Diuréticos/farmacologia , Hidroclorotiazida/farmacologia , Natriurese/efeitos dos fármacos , Potássio/urina , Sódio/urina , Sulfonamidas/farmacologia , Cálcio/urina , Cloretos/urina , Diuréticos/administração & dosagem , Diuréticos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Hidroclorotiazida/administração & dosagem , Hidroclorotiazida/uso terapêutico , Hipertensão/tratamento farmacológico , Sulfonamidas/administração & dosagem , Sulfonamidas/uso terapêutico , TorasemidaRESUMO
From a clinicopharmacological standpoint, the urinary excretory potency of diuretics should be assessed comparatively on the basis of the changes in 24-hour natriuresis, with respect to 24-hour natriuresis after placebo, caused by single oral doses administered to healthy adult subjects who are in habitual and steady-state external sodium balance. The potency of various formulations of loop (e.g., furosemide), of early distal tubular (e.g., the thiazides), and of potassium-retaining diuretics, as well as of several combinations of diuretics, has been evaluated in a series of studies. Two formulations of loop diuretics (muzolimine 20 mg and torasemide 2.5 mg) are definitely nondiuretic. The majority of the other formulations of loop diuretics studied are, in general, comparatively less potent than most of the common formulations of early distal tubular diuretics studied. As a general rule, most common formulations of early distal tubular diuretics are at least not less potent than the majority of common formulations of loop diuretics. Hydrochlorothiazide 25 mg and furosemide 80 mg have similar potencies. Loop diuretics increase mean renal sodium output strikingly within the first few (0-6) hours after dosing, but this forced excretion is followed by a rebound with respect to postplacebo mean urinary sodium flow; the rebound usually takes place between 6 and 24 hours after dosing. However, no rebound in mean urinary sodium flow occurs during the 24 hours following a single dose of a distal tubular diuretic; these substances increase urinary sodium excretion with lower maximal intensity but more protractedly than loop diuretics.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Diuréticos/farmacologia , Natriurese/efeitos dos fármacos , Clopamida/farmacologia , Diuréticos/uso terapêutico , Furosemida/farmacologia , Humanos , Hidroclorotiazida/farmacologia , Muzolimina/farmacologia , Piridinas/farmacologia , Sulfonamidas/farmacologia , Torasemida , Xipamida/farmacologiaRESUMO
The isolated liver perfusion model was used to study the effects of supra-therapeutic doses of rifampicin on hepatic gluconeogenesis and bromosulphthalein (BSP) clearance from the perfusate and biliary excretion of the dye in the rat. Three groups of rats randomly assigned to a control and two experimental groups were studied; those in the experimental groups were given 4 mg rifampicin per os daily for 90 days. The control group was untreated. The livers of the control and one experimental group were perfused with a medium containing pyruvate and subsequently these livers were perfused with a medium containing bromosulphthalein. The livers of the second experimental group were subjected to histological examination. The rate and the concentration of glucose was decreased, lactate levels and lactate: pyruvate ratios were increased in the experimental animals. The mean perfusate BSP and biliary excretion of the dye was decreased in the experimental group. Fatty change was present in the livers of rifampicin treated rats. This study demonstrates that the isolated liver model has proved to be both suitable and useful for the study of the effects of drugs and that chronic administration of supra-therapeutic doses of rifampicin to rats adversely affected liver function. It also produces histological evidence of hepatic damage in rats.
Assuntos
Fígado/efeitos dos fármacos , Modelos Biológicos , Rifampina/farmacologia , Animais , Glucose/biossíntese , Fígado/metabolismo , Fígado/patologia , Masculino , Técnicas de Cultura de Órgãos , Ratos , Ratos Endogâmicos , Sulfobromoftaleína/farmacocinéticaRESUMO
Five groups of rats were studied in an investigation to determine whether changes in the ventricular fibrillation threshold (VFT) occur when ethyl alcohol (EtOH) is given alone or in combination with K+ and/or Mg2+ supplements; the first group (n = 20) served as controls, the second (n = 18) was given only EtOH, the third (n = 18) EtOH+KCl, the fourth (n = 16) EtOH+MgCl2, and the fifth (n = 18) EtOH+MgCl2 + KCl for a 9 month period. Two rats from each group were killed on each day. One rat heart was perfused using the Langendorff apparatus and the other used for tissue electrolyte analyses. A significant fall in the mean VFT (9.7 +/- SD 1.9 mA vs 4.5 +/- 1.6 mA; P less than 0.0001) was noted in the rats given EtOH solution as drinking water for 9 months, and a significant increase in the VFT levels was seen in the Mg(2+)-supplemented group (9.7 +/- 1.9 mA vs 18.9 +/- 4.1 mA; P less than 0.0001) and in the K+ + Mg2+ supplemented group (9.7 +/- 1.9 mA vs 15.8 +/- 1.3 mA; P less than 0.0001) compared to controls. In addition, an increase in the heart rate was observed in the group supplemented with Mg2+ (213 +/- 8 beats/min vs 231 +/- 10 beats/min; P less than 0.0001) as well as in the group supplemented with K+ + Mg2+ (213 +/- 8 beats/min vs 222 +/- 10 beats/min; P less than 0.002) compared to controls. There was no significant change in the coronary blood flow (CF) in any group.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Etanol/toxicidade , Sistema de Condução Cardíaco/efeitos dos fármacos , Cloreto de Magnésio/farmacologia , Potássio/farmacologia , Fibrilação Ventricular/induzido quimicamente , Animais , Circulação Coronária/efeitos dos fármacos , Eletrocardiografia , Etanol/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar/fisiologia , Fibrilação Ventricular/prevenção & controleRESUMO
The excretions of urinary sodium, potassium, magnesium, urate, and water after dosing with diuretics or the angiotensin-converting enzyme inhibitor perindopril are reported, as well as the results of other recent studies. Perindopril in low dose had no significant effect on any of these 24-hour urinary excretions and in high dose, in contrast to captopril and enalapril, does not increase magnesium loss. These effects were studied in healthy volunteers, which may not reflect urinary excretions in hypertensive patients.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Furosemida/farmacologia , Indóis/farmacologia , Urina/química , Adolescente , Adulto , Interações Medicamentosas , Humanos , Magnésio/urina , Perindopril , Valores de Referência , Sódio/urina , Ácido Úrico/urinaRESUMO
This investigation was conducted to determine the influence of hexane on the ventricular fibrillation threshold of the isolated perfused rat heart and myocardial electrolyte levels. Ventricular fibrillation threshold was measured using the Langendorff perfusion apparatus. Heart rate was measured by a universal digital counter and the cardiac flow by collecting the outflow of the heating chamber below the heart into a graduated measuring cylinder. Magnesium and zinc were measured by atomic absorption spectrophotometry and potassium by flame photometry. Two groups of rats were studied; those in the experimental group were given 0.2 ml of hexane and the control group 0.2 ml olive oil subcutaneously for 90 days. Their hearts were removed under anaesthesia. Half of the experimental and control hearts were mounted on the Langendorff perfusion apparatus and the heart rate, coronary flow and ventricular fibrillation threshold were measured. The hearts of the other half were used to measure myocardial electrolyte levels. In the experimental group the ventricular fibrillation threshold decreased (4.72 (S.D. +/- 1.87) vs 9.48 (S.D. +/- 2.98); P less than 0.001). There was no change in the coronary flow and heart rate in between the groups. The mean myocardial potassium levels (2586 (S.D. +/- 162) vs 2968 (S.D. +/- 218) micrograms/g; P less than 0.001), magnesium levels (164 (S.D. +/- 28) vs 208 (S.D. +/- 18) micrograms/g; P less than 0.001) and zinc levels (19.6 (S.D. +/- 4) vs 33.8 (S.D. +/- 6.8) micrograms/g; P less than 0.001) were significantly lower in the hexane-treated group compared to controls. Hexane, a constituent of glue and benzine, is cardiotoxic; marked derangement in myocardial electrolytes and a reduced ventricular fibrillation threshold, indicating an increased myocardial vulnerability to arrhythmias, was noted in the experimental animals.
Assuntos
Coração/efeitos dos fármacos , Hexanos/toxicidade , Miocárdio/química , Fibrilação Ventricular/induzido quimicamente , Animais , Circulação Coronária/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Injeções Subcutâneas , Magnésio/análise , Masculino , Reperfusão Miocárdica , Potássio/análise , Ratos , Ratos Endogâmicos , Fibrilação Ventricular/metabolismo , Zinco/análiseRESUMO
Male patients with supine diastolic blood pressures above 95 mmHg after placebo therapy received twice daily isradipine (Dynacirc; Sandoz) 1.25, 2.5 or 5.0 mg for 12 weeks. Blood pressures were measured every 14 days. Doses of 2.5 or 5 mg isradipine twice daily significantly reduced supine and erect mean systolic, mean diastolic and mean arterial pressures. Isradipine 1.25 mg twice daily reduced supine mean diastolic and mean arterial pressures only. A dose of 5 mg twice daily was accompanied by an increase in adverse reactions. The recommended dose of isradipine is 2.5 mg twice daily.
Assuntos
Anti-Hipertensivos/uso terapêutico , Di-Hidropiridinas/uso terapêutico , Hipertensão/tratamento farmacológico , Anti-Hipertensivos/efeitos adversos , Di-Hidropiridinas/efeitos adversos , Humanos , Isradipino , MasculinoRESUMO
Three groups of rats were studied in an investigation to determine the influence of alcohol on myocardial electrolytes and the ventricular fibrillation threshold (VFT) levels. Drinking water was provided ad libitum; the control group received water while the other 2 groups drank a water-ethanol solution, constituted in a ratio of 75: 25, for periods of 3 and 9 months, respectively. Two rats from each of the experimental groups, together with a control rat were killed on each experimental day. One heart was studied on the Langendorff preparation and the other used for tissue electrolyte analysis. The mean myocardial Mg2+ levels (233 +/- 28 micrograms/g vs 148 +/- 23 micrograms/g and 233 +/- 28 micrograms/g vs 107 +/- 15 micrograms/g; p less than 0.0001), K+ levels (3260 +/- 437 micrograms/g vs 1779 +/- 312 micrograms/g and 3260 +/- 437 micrograms/g vs 1195 +/- 205 micrograms/g; p less than 0.0001) and Zn2+ levels (32.7 +/- 6.8 micrograms/g vs 14.0 +/- 4 micrograms/g and 32.7 +/- 6.8 micrograms/g vs 4.2 +/- 3.4 micrograms/g; p less than 0.0001) were significantly lower in alcohol fed rats than the controls. In addition, a significant fall in the mean VFT levels (10.1 +/- 1.94 mA vs 6.27 +/- 2.17 mA, p less than 0.001) was noted in rats given water: alcohol solution for 9 months. This study reveals that chronic exposure to alcohol induces a deficiency of myocardial Mg2+, K+ and Zn2+, and an increase in myocardial irritability in laboratory rats.
Assuntos
Eletrólitos/metabolismo , Etanol/toxicidade , Miocárdio/metabolismo , Fibrilação Ventricular/induzido quimicamente , Animais , Coração/efeitos dos fármacos , Técnicas In Vitro , Magnésio/metabolismo , Masculino , Miocárdio/patologia , Ratos , Ratos Endogâmicos , Sódio/metabolismo , Fibrilação Ventricular/metabolismo , Fibrilação Ventricular/patologia , Zinco/metabolismoRESUMO
Forty-five patients with supine diastolic blood pressures (DBPs) above 95 mm Hg at the end of a four-week placebo run-in period were randomized to receive either 1.25 mg, 2.5 mg, or 5 mg isradipine twice daily as monotherapy for 12 weeks. Blood pressures (BP) were measured every 14 days, always by the same observer and using standard techniques. The Montevideo Mathematical Model was used to determine the time course of the response to treatment in each dosage group. Of the 33 patients who completed the study, four of the 12 patients receiving 1.25 mg isradipine twice daily had their BP controlled by weeks 10 or 12 (supine DBP less than or equal to 90 mm Hg), seven of 11 by 2.5 mg twice daily, and five of 10 by 5 mg twice daily. Mean DBPs for each dosage group were significantly reduced by week 12 (P less than .015 in all groups). The Montevideo Model allows estimation of the time after onset of treatment by which BP is reduced by a given amount. This model indicated that, with 2.5 mg isradipine twice daily, a fall in mean arterial pressure of 10 mm Hg is to be expected within three weeks of initiating drug administration.
Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Piridinas/uso terapêutico , Administração Oral , Adulto , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipertensão/fisiopatologia , Isradipino , Masculino , Matemática , Pessoa de Meia-Idade , Modelos Biológicos , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Fatores de TempoRESUMO
The responses of urine and urinary solute outputs and flows to single doses of 80 mg furosemide, 25 mg hydrochlorothiazide, and 100 or 200 mg flosequinan were investigated in healthy subjects using a double-blind, randomized, crossover design. Treatment days were separated by 7 days. Volumes of urine passed between 0 and 3, 3 and 6, 6 and 9, 9 and 12, and 12 and 24 h after drug administration were determined and urinary concentrations of chloride, sodium, potassium, calcium, magnesium, phosphate, zinc, urate, urea and creatinine were measured. Venous blood was taken before and 6 and 24 h after dosing and the serum was analysed for the same solutes as urine. Excretions of urine and urinary solutes accumulated at the end of each collection period after each formulation were fitted by the UY function, whose derivative provided corresponding flows as functions of time. Instantaneous renal clearances of solutes 6 and 24 h after dosing were evaluated from the flows. This approach showed that 80 mg furosemide and 25 mg hydrochlorothiazide were equipotent 24-h natriuretics. Rapid urinary responses which then rebounded compared with the control responses were produced by 80 mg furosemide, whereas changes after 25 mg hydrochlorothiazide were smooth. Neither 100 or 200 mg flosequinan showed any important effect on urinary excretion.
Assuntos
Diuréticos , Furosemida/farmacologia , Hidroclorotiazida/farmacologia , Rim/efeitos dos fármacos , Quinolinas/farmacologia , Vasodilatadores/farmacologia , Adolescente , Adulto , Relação Dose-Resposta a Droga , Humanos , Masculino , Modelos Estatísticos , Urina/análiseRESUMO
A double-blind, parallel-group study was performed to assess the antihypertensive effects and tolerability of felodipine and hydrochlorothiazide (HCT) in black patients with mild to moderate uncomplicated hypertension [entry supine diastolic blood pressure (DBP) of 96-116 mm Hg]. The medicines were given as monotherapy and the additional effect of metoprolol was assessed in patients unresponsive to felodipine or HCT alone. After a 4-week placebo period, 45 patients were randomly allocated to treatment with felodipine (21) or HCT (24). Initial doses of felodipine 2.5 mg or HCT 12.5 mg twice daily were doubled after 1 week and doubled again after week 4 in cases with supine DBP above 90 mm Hg. At week 8, metoprolol 100 mg twice daily was added to the regimen of uncontrolled patients (supine DBP greater than 90 mm Hg) and maintained for the remaining 4-week trial period. Felodipine significantly reduced supine and erect systolic BP (SBP) and DBP after 4, 8, and 12 weeks of treatment. Responses to HCT were similar although standing diastolic BP at week 4 and standing SBP at week 8 were not significantly reduced. After 4 weeks, the mean fall in supine DBP was significantly greater for the felodipine than the HCT group. Eight patients on felodipine and 14 in the HCT group required additional metoprolol to achieve BP control. A significantly greater number of adverse effects were associated with HCT than felodipine treatment. Monotherapy with felodipine produced a more rapid control of hypertension, was more frequently effective, and was associated with a lower incidence of side effects than HCT.
Assuntos
Felodipino/uso terapêutico , Hidroclorotiazida/uso terapêutico , Hipertensão/tratamento farmacológico , Adulto , África , População Negra , Pressão Sanguínea/efeitos dos fármacos , Método Duplo-Cego , Felodipino/administração & dosagem , Felodipino/efeitos adversos , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hidroclorotiazida/administração & dosagem , Hidroclorotiazida/efeitos adversos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
The acute renal excretory actions of several antihypertensive agents were assessed in healthy volunteers. Rilmenidine (1 mg) did not affect water and electrolyte balance. Beta-adrenergic blockers had little effect upon urinary composition, whereas diuretics caused significant urinary losses of fluid, sodium, potassium, and magnesium as expected. The vasodilators ketanserin and flosequinan did not affect water and electrolyte excretion. Ketanserin increased urate output in common with angiotensin-converting enzyme inhibitors, which may act as facultative diuretics. Combining the angiotensin-converting enzyme inhibitor captopril (100 mg) or rilmenidine (1 mg) with hydrochlorothiazide (25 mg) had little influence upon the known actions of the diuretic. When the beta-blocker pindolol (10 mg) was given with the diuretic clopamide (5 mg), beneficial effects were noted; potassium and magnesium losses were markedly reduced, whereas the natriuretic and diuretic effects of clopamide were unchanged. These short-term studies in healthy volunteers provide useful pointers to some possible pharmacodynamic effects of antihypertensive drugs in patients.
Assuntos
Anti-Hipertensivos/farmacologia , Rim/efeitos dos fármacos , Oxazóis/farmacologia , Adolescente , Antagonistas Adrenérgicos beta/farmacologia , Adulto , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Diuréticos/farmacologia , Método Duplo-Cego , Interações Medicamentosas , Eletrólitos/urina , Humanos , Hidroclorotiazida/farmacologia , Masculino , Rilmenidina , Vasodilatadores/farmacologiaRESUMO
The efficacy of diltiazem (DTZ) (Tilazem; Parke-Davis) 90-180 mg twice daily was compared with that of hydrochlorothiazide (HCT) 25-50 mg once daily in the monotherapy of mild-to-moderate essential hypertension using a double-blind, double-dummy technique. Twenty-nine patients were randomly assigned to two groups and after a 4-week placebo period treated with HCT 25 mg once daily or DTZ 90 mg twice daily for 12 weeks. Dosage was doubled at week 8 in non-responders. Cross-over of therapy took place after a 4-week placebo washout. Both drugs effectively reduced raised arterial pressures with little change in pulse rate. HCT caused a slight elevation of the mean serum urate level. The study confirms that diltiazem offers an effective well-tolerated monotherapy for essential hypertension.