摘要:

Clinical Pharmacology and Therapeutics(1984)36,151–156; doi:10.1038/clpt.1984.1

ISSN:0009-9236    

DOI:10.1038/clpt.1984.154

年代:1984

数据来源: WILEY

摘要:

Clinical Pharmacology and Therapeutics(1984)36,156; doi:10.1038/clpt.1984.155

ISSN:0009-9236    

DOI:10.1038/clpt.1984.155

年代:1984

数据来源: WILEY

摘要:

We report on serum lipoprotein changes after antihypertensive therapy in nine subjects with type II hyperlipoproteinemia and eight subjects with normolipidemia. They received placebo for 6 wk, followed by random order crossover between methyldopa and propranolol for 6 mo. Physical activity, diet, and other drugs were monitored for constancy. No other antihypertensive drugs were used. Doses required for normalization of blood pressure ranged between 40 to 360 mg/day for propranolol and 500 to 2500 mg/day for methyldopa. Mean blood pressure was equally lowered to normal by both drugs. Triglyceride levels increased after propranolol and after methyldopa. Subjects with normocholesterolemia developed higher serum triglyceride levels after each drug, whereas such a change did not occur in patients with hypercholesterolemia. Low‐density lipoprotein cholesterol levels were reduced by methyldopa only in patients with baseline hypercholesterolemia. There was no correlation between lipoprotein level changes, dose required of either drug, or propranolol blood levels. The baseline lipoprotein metabolism disorder appears more likely to determine the type of changes in serum lipoprotein levels after these antihypertensive drugs.Clinical Pharmacology and Therapeutics(1984)36,157–162; doi:10.1038/clpt.1984

ISSN:0009-9236    

DOI:10.1038/clpt.1984.156

年代:1984

数据来源: WILEY

摘要:

Propafenone disposition kinetics were studied after intravenous and oral doses in patients with ventricular arrhythmias. Plasma concentration–time data were fit to a two‐compartment model for all but one patient, whose data required fitting to a three‐compartment model. The model‐independent calculated values of clearance, steady‐state volume of distribution, and terminal t½ were 11.2 ± 4.8 ml/min/kg, 3.6 ± 2.1 l/kg, and 5.0 ± 3.6 hr. After 5 days on oral propafenone, elimination t½ was 6.2 ± 3.3 hr. The longer t½s and the estimates of steady‐state bioavailability above 100% suggests that clearance decreases during chronic oral dosing. Considerable intersubject variability was noted in all disposition parameters.Clinical Pharmacology and Therapeutics(1984)36,163–168; doi:

ISSN:0009-9236    

DOI:10.1038/clpt.1984.157

年代:1984

数据来源: WILEY

摘要:

Ten subjects with hypertension received medroxalol, which blocks both α‐ and β‐adrenergic receptors, has intrinsic sympathomimetic β2‐agonist properties and is a direct vasodilator. Renal function tests consisting of inulin clearance and p‐amino hippuric acid (PAH) clearance, plasma renin activity (PRA) in recumbent and upright postures, and aldosterone excretion rate were performed. After intravenous medroxalol, inulin clearance and PAH clearance rose, renal vascular resistance fell, recumbent PRA was unchanged, and the rise in PRA with upright posture was blunted. After 1 mo on oral medroxalol, blood pressure was controlled while inulin clearance, PAH clearance, and renal vascular resistance were unchanged. The rise in PRA with upright posture remained blunted. Urinary aldosterone excretion was unchanged after 1 mo on medroxalol.Clinical Pharmacology and Therapeutics(1984)36,169–173; doi:10.1038/

ISSN:0009-9236    

DOI:10.1038/clpt.1984.158

年代:1984

数据来源: WILEY

摘要:

In a single‐blind, randomized study, the cardiovascular and metabolic effects of sotalol, 40 to 160 mg/day, in six patients with mild essential hypertension were compared to those of placebo at rest and during submaximal dynamic exercise. Resting blood pressure was controlled by sotalol but not the pressor response to exercise, despite reduction of tachycardia. The major metabolic finding on sotalol was an approximately 40% decrease in lipid mobilization during exercise. Alterations in muscle lactate concentrations were much like those caused by other β‐blockers. Plasma concentrations of norepinephrine and epinephrine were doubled during exercise on sotalol, epinephrine disposition more so. No effects on serum lipoproteins were observed after 6 wk on sotalol in therapeutic doses. Despite its special electrophysiologic properties, sotalol appears to induce the same cardiovascular and metabolic changes during exercise as do other β‐blockers.Clinical Pharmacology and Therapeutics(1984)36,174–182; doi:10.1038/clp

ISSN:0009-9236    

DOI:10.1038/clpt.1984.159

年代:1984

数据来源: WILEY

摘要:

To study the interaction between the calcium antagonist diltiazem and digoxin, a randomized crossover trial under steady‐state conditions was carried out in 24 healthy male subjects. Diltiazem with digoxin induced an average increase of steady‐state plasma digoxin concentration and AUC over 48 hr of 22.4%. This is caused by the prolongation of elimination t½ from 36.2 ± 11.2 to 44.5 ± 11.5 hr (X̄ ± SD) and the impairment of total digoxin clearance, dropping from 146.6 ± 37.9 to 107.9 ± 18.4 ml/min. Average reduction in renal clearance (from 102.1 ± 35.5 to 85.5 ± 42.7 ml/min) was not statistically reproducible. Apparent volume of distribution was not relevantly altered. Diltiazem kinetics did not change significantly when digoxin was concurrently given.Clinical Pharmacology and Therapeutics(1984)36,183–189; doi:10.103

ISSN:0009-9236    

DOI:10.1038/clpt.1984.160

年代:1984

数据来源: WILEY

摘要:

The imidazoline derivative idazoxan, which has been shown to be a potent, selective α2‐adrenoceptor antagonist, was injected intravenously to eight men with normotension. There was a transient small increase in blood pressure and a decrease in heart rate within 20 min of injection, with a slight increase in plasma norepinephrine levels. These effects are consistent with antagonism of prejunctional α2‐adrenoceptors. In response to infusions of the relatively selective α2‐adrenoceptor agonist α‐methylnorepinephrine, the pressor dose‐response curve shifted to the right with idazoxan. These data provide evidence for receptors with α2‐adrenoceptor characteristics on resistance vessels in man. In vitro platelet aggregation studies provide further evidence of selective α2‐adrenoceptor antagonism by idazoxan, with greater potency and affinity than α‐yohimbine. These observations are consistent with both pre‐and postjunctional peripheral α2‐adrenoceptors in man and provide further support that idazoxan is a selective α2‐adrenoceptor antagonist.Clinical Pharmacology and Therapeutics(1984)36,190

ISSN:0009-9236    

DOI:10.1038/clpt.1984.161

年代:1984

数据来源: WILEY

摘要:

Several studies have shown that 5 mg amiloride can counteract the hypokalemic effect of 50 mg hydrochlorothiazide (HCTZ). In a double‐blind study of 30 subjects with mild to moderate primary hypertension, we determined whether this effect could be obtained with half the dose of amiloride (2.5 mg) in combination with 25 mg HCTZ. The effect of twice the dosage was evaluated in subjects with unsatisfactory blood pressure (BP) on the lower dose. Both 25 mg HCTZ/amiloride 2.5 mg and 25 mg HCTZ alone lowered BP. In subjects with untreated diastolic BP between 110 and 115 mm Hg, these doses were inadequate; twice the dose resulted in a greater reduction in BP. Irrespective of dosage, a potassium‐sparing effect resulted from the combination of HCTZ and amiloride, with a reduction in serum potassium levels from HCTZ alone as well.Clinical Pharmacology and Therapeutics(1984)36,197–200; doi:10.1038/clpt.19

ISSN:0009-9236    

DOI:10.1038/clpt.1984.162

年代:1984

数据来源: WILEY

摘要:

Serum protein binding was measured in six women 38 wk pregnant and in five control subjects. Three distinct binding sites for drugs on human serum albumin have been identified. To determine whether changes in binding during pregnancy occur for common drugs or only for drugs that bind to a specific binding site, serum protein binding of three drugs—diazepam (site I), warfarin (site III), and salicylate—and four fluorescent probes—dansylsarcosine (site I), l‐anilino‐8‐naphthalenesulfonate (site I), 7‐anilinocoumarin‐4‐acetic acid (site II), and 5‐dimethylaminonaphthalene‐1‐sulfonamide (DNSA) (site III)—were determined in control and pregnant sera. Unbound fractions of diazepam and salicylate in pregnant women increased but the unbound fraction of warfarin did not change. Dissociation constants (Kd1) of all fluorescent probes but DNSA were almost the same in control and pregnant sera, while the Kd1of DNSA in pregnant serum was approximately 50% of control. Binding capacities of all probes decreased, which was attributed to decreased serum albumin concentration. We concluded that serum protein binding of drugs that bind to site I or site II on albumin decreased largely because of the reduced serum albumin concentration during pregnancy and that the binding of drugs that bind to site III changed little because of compensating effects of the decrease in serum albumin concentration and the increase in binding affinity to serum albumin. Serum concentration of α1‐acid glycoprotein and serum binding of propranolol did not change in pregnant women.Clinical Pharmacology and Therapeutics(1984)36,201

ISSN:0009-9236    

DOI:10.1038/clpt.1984.163

年代:1984

数据来源: WILEY