Because of the low levels of captopril in breastmilk, amounts ingested by the infant are small and would not be expected to cause any adverse effects in breastfed infants.

Hydrochlorothiazide doses of 50 mg daily or less are acceptable during lactation. Intense diuresis with large doses may decrease breastmilk production.

Clinical effectiveness and tolerability of o.d. use of fixed dose combinations of perindopril (4 mg) with indapamide (1.25 mg) (Noliprel forte) and captopril (50 mg) with hydrochlorothiazide (25 mg) (Capozide) were compared in a randomized study on 40 patients with I-II degree high and very high risk hypertension. Study duration was 6 months, number of patients in each of parallel groups -- 20. Antihypertensive activity, ability to decrease left ventricular hypertrophy, to improve arterial elasticity and T/P parameter of perindopril (4 mg) -- indapamide (1.25 mg) combination was found to be superior to those of captopril (50 mg) -- hydrochlorothiazide (25 mg) combination.

Clinical effectiveness and tolerability of o.d. use of fixed dose combinations of enalapril (10 mg) with hydrochlorothiazide (25 mg) (Enap H) and captopril (50 mg) with hydrochlorothiazide (25 mg) (Capozide) were compared in a randomized study on 60 patients with I-II degree high and very high risk hypertension. Study duration was 6 months, number of patients in each of parallel groups -- 30. Antihypertensive activity, ability to improve arterial elasticity and T/P parameter, cost/efficacy index of enalapril (10 mg) plus hydrochlorothiazide (25 mg) combination was found to be superior to those of captopril (50 mg) plus hydrochlorothiazide (25 mg) combination.

Monotherapy with caposide-50 (C-50) was compared to combined therapy C-50 + melatonin in 22 patients with essential hypertension stage II (mean age 60 years). The patients were divided into two groups. Group 1 received C-50 at 8.00 a.m., group 2 received C-50 at 8.00 a.m. and melatonin at 10.00 p.m. in a dose 3 mg. Before the treatment and 14 days after it echo-CG was made to assess hemodynamics. Also, 24-h monitoring of arterial pressure was performed. The findings were analysed with variance statistics and cosinor-analysis. Group 1 achieved a moderate hypotensive effect. Circadian rhythm of systolic blood pressure was abnormal. Group 2 patients achieved more pronounced decline of systolic, diastolic and mean arterial pressures. Circadian rhythm of these pressure did not return to normal.

The main parameters considered in optimizing the liquid extraction and quantitative assay were the yield, precision, limit of quantification, time required for extraction and concentration, and quantity of solvent. The influence on these parameters of the following factors was examined: nature of the extracting solvent, quantity of solvent, co-extraction solvent, and duration of stirring. Instead of equilibrium parameters of the involved thermodynamic system, a kinetic approach was preferred in terms of the effective partition 'constant', which is not really constant but a function of time and extraction conditions. The final selected method, considered to be rapid and simple, was applied to determine the pharmacokinetics of hydrochlorotiazide (HCT) after administration of Capozide (Bristol-Myers Squibb) tablets containing 50 mg Captopril and 25 mg HCT, to 4 healthy volunteers. The results obtained were in accordance with the pharmacokinetic parameters of HCT reported in the literature.

This study compared the antihypertensive efficacy and tolerability of a combination tablet containing the vascular-selective calcium antagonist felodipine and the beta1-selective adrenergic antagonist metoprolol, with a combination tablet of captopril-hydrochlorothiazide in a randomized, double-blind trial involving 109 patients with mild to moderate hypertension. After 2 weeks on placebo, patients with a supine diastolic blood pressure of 95-115 mm Hg were randomized to felodipine-metoprolol, 5/50 mg o.d. (Logimax) or captopril-hydrochlorothiazide, 25/25 mg o.d. (Capozide). After a further 4 weeks, there was a mandatory dose increase to felodipine-metoprolol 10/100 mg o.d., and captopril-hydrochlorothiazide, 50/25 mg o.d., and treatment then continued for a another 4 weeks. At the end of the study, felodipine-metoprolol reduced supine blood pressure significantly more than captopril-hydrochlorothiazide. The mean differences in change in supine systolic and diastolic blood pressure between treatments after 8 weeks were 5.2 and 3.4 mm Hg, respectively, in favour of felodipine-metoprolol (p<0.05). Standing blood pressure also showed trends in favour of felodipine-metoprolol. The proportion of responders was similar in both groups. Both treatments were well tolerated. Two patients treated with felodipine-metoprolol and 5 with captopril-hydrochlorothiazide discontinued treatment due to adverse events. Felodipine-metoprolol combination reduced supine blood pressure significantly more than captopril-hydrochlorothiazide with maintained tolerability.

Only approximately 40% to 50% of hypertensive patients will achieve goal blood pressures of <140/ 90 mm Hg with monotherapy, regardless of the medication used. Fixed-dose combination therapy with two different classes of antihypertensive agents will achieve goal pressures in more than 70%. The sixth Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure has suggested that the use of combination therapy is appropriate as initial treatment. The advantages of combinations include: 1) greater blood pressure decrease and response rates than monotherapy; 2) fewer side effects with small doses of two drugs than with large doses of one agent; 3) improved adherence to treatment; and 4) possibly lower cost of therapy. Many different combinations of diuretics and beta-blockers, angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists, as well as ACE inhibitors and calcium antagonists are available. Two of these, Ziac and Capozide, have been approved as initial therapy. It is possible that the number of hypertensive individuals controlled at goal blood pressure levels will be increased if combination therapy is used as initial treatment.

The renin-angiotensin system is associated with a variety of pathophysiological processes in many organ systems, and is known to be involved in the normal regulation of blood pressure and in the pathogenesis of renovascular hypertension. Angiotensin II is a multifunctional hormone that manifests its properties by interacting with two major subtypes of cell surface receptors (AT1 and AT2). Angiotensin converting enzyme (ACE) inhibitors are able to modify the actions of the renin-angiotensin system, and are indicated for the treatment of hypertension and heart disease. The antihypertensive effects of ACE inhibiting drugs are related to their ability to block the conversion of the decapeptide, angiotensin I, to the potent pressor octapeptide, angiotensin II. ACE inhibitors have been implicated in fetopathies in humans and perinatal mortality in rats, rabbits, sheep and baboons. Human fetopathies were seen when ACE inhibitors were given around the 26th week of gestation. The major adverse effects in babies include: oligohydramnios, renal tubular dysgenesis, neonatal anuria, calvarial and pulmonary hypoplasia, mild to severe intrauterine growth retardation, persistent patent ductus arteriosus and fetal or neonatal death. These developmental anomalies are thought to be partly due to a direct action of ACE inhibitors on the fetal renin-angiotensin system and partly due to the ischemia resulting from maternal hypotension and decreases in fetal-placental blood flow and oxygen/nutrient delivery to the fetus. The purpose of this review is to briefly discuss the pathophysiological role of the renin-angiotensin system, the therapeutic uses of ACE inhibitors in pregnant patients and to focus primarily on the major fetotoxic effects of ACE inhibitors encountered in humans and animal models. I will also review our recent data which show that capozide (captopril + hydrochlorothiazide) not only produces oligohydramnios but also disturbs the balance of glucose and NaCl in the maternal plasma and amniotic fluid of the rat.

The effect of Capozide, the combination of captopril with a hydrochlorothiazide diuretic, on voluntary alcohol intake was assessed in two experiments. In experiment 1 naive rats who were maintained on ad libitum food and water were given daily 40-min access to a 6% (w/v) alcohol solution and water. Daily intraperitoneal injections of captopril (10 mg/kg) reduced alcohol intake, but the combination of captopril (5 and 10 mg/kg) and hydrochlorothiazide (2.5, 5, and 10 mg/kg) enhanced the reduction in intake. In experiment 2, captopril alone, hydrochlorothiazide alone, and the combination of captopril and hydrochlorothiazide were again administered daily in the limited access procedure. Captopril (10 mg/kg) again reduced alcohol intake as did all three doses of hydrochlorothiazide (2.5, 5, and 10 mg/kg). Compared with the individual effects of captopril and hydrochlorothiazide, Capozide exerted a supra-additive reduction in alcohol intake. These effects were not due to drug-induced changes in the pharmacokinetics of alcohol. Taken together these results demonstrate an enhanced potency of Capozide in suppressing alcohol intake and invite their testing in a population of hypertensive alcoholics and alcohol abusers.

An open multicenter trial involving 7,232 participating physicians, was performed to assess the anti-hypertensive efficacy and tolerance of a fixed combination of captopril and hydrochlorothiazide (Capozide) given once daily to 34,976 patients (mean age 58.5 +/- 11.4 years) with mild-to-moderate hypertension inadequately controlled by previous anti-hypertensive treatment. After 8 weeks, the response rate to a daily dose of Capozide 25 or 50 was 87.2%. Within this period, the mean systolic/diastolic blood pressure dropped from 175 +/- 16/103 +/- 5 mmHg to 150 +/- 13/88 +/- 7 mmHg (p less than 0.001). In 81% of the questionnaires, treatment with the combination was rated superior to the previous treatment; in only 5% was it considered inadequate. Side effects, for the most part mild, were reported by 7.4% of the patients. Treatment with Capozide was discontinued, or another form of treatment substituted in 12.9% of the cases.

Three simple, rapid and sensitive methods for the assay of captopril which is an effective alternative to digitalis were developed. These methods are based on the oxidation reaction in aqueous solution of captopril with either ferric chloride or iodine. The indirect quantitation of the product was carried out at 523, 351 and 620 nm for ferro-bipyridyl, residual iodine and residual iodine-starch complex, respectively. All variables were studied to optimize the reaction conditions. Regression analysis of Beer's plot showed good correlation in a general concentration range of 0.25-25 mug captopril/ml. No interference was observed from hydrochlorothiazide diuretic which was recently introduced in combination with captopril or other common pharmaceutical adjuvants. The validity of the methods was tested by analysing capoten and capozide tablets. Recoveries were 99.1-102.8%.