摘要:

A study of adherence to treatment was conducted by 179 general practitioners in elderly outpatients with geriatric cerebral symptomatology treated with pentoxifylline. The drug was provided in 2 different randomized packages, with or without memory‐aid stickers (also randomized). Compliance was assessed by pill count after 1 mo of treatment. Clinical evolution was assessed by a digit‐span test, and by filling in 9 “relative” visual analogue scales of aggravation—improvement. Side effects were recorded from patient complaints. Leftover drug was brought back by 83.1% of patients, and this proportion was influenced neither by packaging type nor memory‐aid stickers. Compliance was considered good (fewer than 30 tablets returned) in 62% of patients, and was not influenced by either packaging types or stickers. Peaks of pill count were evident at multiples of packaging units (10 or 40 according to type). Compliance was not related to age or sex, but was related to memory score. There was a correlation between compliance and clinical improvement, and a significant inverse correlation between the former and the frequency of side effects.Clinical Pharmacology and Therapeutics(1980)27,1–8; doi:10.10

ISSN:0009-9236    

DOI:10.1038/clpt.1980.1

年代:1980

数据来源: WILEY

摘要:

In 26 patients with essential hypertension who were on continuous chlorthalidone therapy, 1 and 3 daily doses of propranolol were compared in a crossover study. Plasma propranolol levels and heart rates had larger daily fluctuations on single‐dose therapy than on 3 times daily; plasma renin activity was more constant. There was no significant difference in blood pressures. Once‐daily propranolol dosage was well tolerated and possibly gave less rise to the troublesome side effect of vivid dreaming.Clinical Pharmacology and Therapeutics(1980)27,9–15; doi:10.1038/clpt.

ISSN:0009-9236    

DOI:10.1038/clpt.1980.2

年代:1980

数据来源: WILEY

摘要:

3H‐digoxin‐12α and unlabeled digoxin were administered down a nasogastric tube and digoxin, digoxigenin and its mono‐ and bis‐digitoxosides, and pH were assayed in gastric fluid of 6 healthy subjects at intervals for 90 min each under 4 conditions: pentagastrin infusion 6 μg/kg/hr with the subjects ambulatory and supine, and saline infusion ambulatory and supine, intragastric hydrolysis occurred at roughly the same rate as reported in vitro. At 90 min, an average of 12.5% of the radioactivity that remained in the gastric fluid was recovered as digoxin for the 2 conditions when pentagastrin was infused, compared with 52.5% for the 2 conditions when saline was infused. The main glycosidic metabolite was digoxigenin and the amount correlated closely with the hydrogen ion activity in gastric fluid at 90 min (r = 0.83, p<0.01). Only minor differences were found between the supine and ambulatory conditions. The clinical significance of these results remains to be determined.Clinical Pharmacology and Therapeutics(1980)27,16–21; doi:10.1038

ISSN:0009-9236    

DOI:10.1038/clpt.1980.3

年代:1980

数据来源: WILEY

摘要:

The disposition of the pharmacologically active 4‐hydroxypropranolol (HO‐P), its glucuronic acid conjugate (HO‐P‐G), and propranolol were compared after single intravenous and oral doses of propranolol in 6 normal subjects and after long‐term therapy in 32 patients with hypertension or coronary artery disease. The areas under the plasma concentration/time curves (AUC∞, ng · hr/ml) after 4‐mg intravenous doses of propranolol were 6.6 ± 2.2 (mean ± SEM) for HO‐P and 55 ± 11 for propranolol. After 20‐ and 80‐mg oral doses the AUC∞for HO‐P were 59 ± 9 and 162 ± 21 and for propranolol were 72 ± 9 and 306 ± 46. Peak HO‐P concentrations were reached at 1 to 1.5 hr after the oral doses. Although there was a rapid decline in plasma HO‐P between 1.5 and 3 hr when HO‐P‐G was still rising to levels above HO‐P levels 3.5‐ to 5‐fold, the apparent half‐lifes (t½s) after 3 hr were in the same range for HO‐P, HO‐P‐G, and propranolol (3.0 to 4.2 hr). While during long‐term therapy plasma HO‐P rose over the whole dose range (40 to 960 mg daily) in an apparently linear fashion, the HO‐P/propranolol plasma level ratio fell from 1.07 ± 0.13 at 40 mg daily to only 0.09 ± 0.01 at 640 mg daily. Plasma HO‐P‐G rose exponentially with dose and demonstrated significant cumulation. HO‐P and HO‐P‐G in urine accounted for about 9% of long‐term propranolol doses. This study suggests a significant contribution of HO‐P to pharmacologic effects, in particular at low single and long‐term oral doses of propranolol and saturation of naphthalene ring oxidation as a main determinant of propranolol bioavailabilit

ISSN:0009-9236    

DOI:10.1038/clpt.1980.4

年代:1980

数据来源: WILEY

摘要:

Patients undergoing surgical procedures using sodium nitroprusside‐induced hypotension were studied to determine the role of the renin‐angiotensin system in the pathogenesis of rebound hypertension (RH) after discontinuing sodium nitroprusside (SNP) infusion. Retrospective observations documented RH in 9 of 12 patients (group I) with a systolic blood pressure (SBP) increase from 112 ± 3.92 before SNP to 144 ± 5.60 torr 10 min after SNP (p<0.001). In 12 patients (group II), plasma renin activity (PRA) rose from 950 ± 432 to 3,611 ± 1,874 pg/ml/hr (p<0.0005) during SNP and remained elevated (2,504 ± 792 pg/ml/hr) 30 min after cessation of SNP. SBP rose from a control (pre‐SNP) value of 112 ± 5.24 to 129 ± 8.52 torr after discontinuation of SNP (p<0.05). Significant PRA and SBP changes did not occur in a matched group of patients (group III) who did not receive SNP. That RH after cessation of SNP infusion was associated with persistent elevation of PRA leads us to suggest that RH may be attributable to the unopposed effects of the renin‐angiotensin system after the rapid plasma disappearance of SNP.Clinical Pharmacology and Therapeutics(1980)27,32–36; doi:10

ISSN:0009-9236    

DOI:10.1038/clpt.1980.5

年代:1980

数据来源: WILEY

摘要:

The serum levels of methyldopa and its principle metabolites were assessed in 22 hypertensive children, of whom 13 had impaired renal function. A significant correlation was found between the magnitude of the renal dysfunction and the serum levels of methyldopa, α‐methyldopa‐sulfate, α‐methyldopamine, and α‐methyldopamine‐sulfate. The patients were divided into 2 groups: those with normal (serum creatinine ≤ 1.0 mg/100 ml) and those with abnormal (serum creatinine>1.0 mg/100 ml) renal function. The serum level of α‐methyldopa‐sulfate and not of methyldopa was elevated in those with renal dysfunction. The serum levels of α‐methyldopamine and, in particular, its 3‐0‐sulfate conjugate were markedly elevated in patients with renal disease. These data suggest that the enhanced sensitivity to methyldopa in patients with impaired renal function may be due in part to α‐methyldopamine.Clinical Pharmacology and Therapeutics(1980)27,

ISSN:0009-9236    

DOI:10.1038/clpt.1980.6

年代:1980

数据来源: WILEY

摘要:

Capsules containing either 16 or 32 mg of14C‐guanabenz were given to 8 hypertensive patients. Maximum concentrations of guanabenz in plasma (1.2 to 5.2 ng/ml) were reached at 2 to 5 hr after dosing.14C elimination into urine was 79.7 ± 10.6% (SD) and 76.7 ± 7.4% of the dose after the 16‐ and 32‐mg doses, respectively, while guanabenz accounted for less than 1% after either dose. Kinetic parameters for guanabenz were estimated by fitting the plasma and urinary data to a 2‐compartment model. After the 16‐mg dose, the elimination half‐life (t½) was 14 ± 5 hr, volume of distribution in the central compartment (Vc) was 5.0 ± 2.2 kl, and total plasma clearance (Clp) was 8 ± 4l/min. After the 32‐mg dose, t½ was 12 ± 3 hr, Vcwas 7.5 ± 1.8 kl, and Clp, was 17 ± 6l/min. No statistically significant difference, except of total plasma clearance, was observed between any of the parameters followed after the 2 doses. (E)‐p‐Hydroxyguanabenz (unconjugated and as a glucuronide) was the major metabolite and accounted for 35.4 ± 3.0% of the urinary radioactivity. Minor amounts of guanabenz and 2,6‐dichlorobenzyl alcohol after β‐glucuronidase hydrolysis indicated thatN‐glucuronidation and cleavage at the benzol carbon were minor metabolic pathways. The drug effectively lowered blood pressure in the hypertensive patients; no other significant effects were noted.Clinical Pharmacology and Therapeutics(19

ISSN:0009-9236    

DOI:10.1038/clpt.1980.7

年代:1980

数据来源: WILEY

摘要:

The effects of 2 potassium‐retaining diuretics on arterial pressure, intravascular volume, responses of the renin‐angiotensin‐aldosterone system, serum electrolytes, and renal function were compared by means of an 8‐wk double‐blind, crossover trial in 13 patients with “volume‐dependent” essential hypertension. The fall in systolic, diastolic, and mean arterial pressures in the supine and erect positions (all p<0.005) induced by spironolactone was greater than that by triamterene. The pressure fall induced by spironolactone was also associated with a persistent contraction in plasma volume (p<0.05) and a secondary hyperaldosteronism that was not accompanied by hypokalemic alkalosis. The pressure fall induced by triamterene was not associated with reduced plasma volume, effect on plasma renin activity, or aldosterone excretion. Both drugs produced significant rises in blood urea nitrogen and creatinine levels that never exceeded normal limits.Clinical Pharmacology and Therapeutics(1980)27,53–56; doi:1

ISSN:0009-9236    

DOI:10.1038/clpt.1980.8

年代:1980

数据来源: WILEY

摘要:

Nadolol, a nonselective beta adrenoceptor antagonist, was evaluated in 9 normal subjects with essential hypertension for ability to inhibit exercise‐induced changes in double‐product (systolic pressure × heart rate). Propranolol and placebo were included as positive and negative controls. The beta antagonists were administered orally in single doses at 10, 20, 40, and 80 mg on a crossover basis. Both nadolol and propranolol induced comparable dose‐related inhibition of double‐product. Duration of beta receptor blockade was greater with nadolol than with propranolol; significant inhibition of double‐product occurred 24 hr after a single 80‐mg dose of nadolol. The antihypertensive effect of nadolol was evaluated in another series of 46 subjects with essential hypertension. The dose of nadolol ranged from 80 to 320 mg once daily. Consistent decreases in supine heart rate (20%) and diastolic blood pressure (9%) from baseline were observed. During steady state, the oral daily dose of nadolol was proportional to the minimum steady‐state serum concentration (Cmin) of nadolol (r = 0.75, p<0.001) obtained just before the next dose of nadolol. Statistically significant correlation was observed between the antihypertensive effect and the Cminfor nadolol (r = 0.45, p<0.05).Clinical Pharmacology and Therapeutics(1980)27,57–63; doi:10

ISSN:0009-9236    

DOI:10.1038/clpt.1980.9

年代:1980

数据来源: WILEY

摘要:

Tocainide is structurally related to lidocaine but may be used orally as well as intravenously. A therapeutic plasma concentration range of 25 to 45 μmole/lhas been suggested. Tocainide kinetics were studied in 6 healthy subjects and 16 patients with acute myocardial infarction. There was good accordance in kinetics of healthy subjects and patients. After intravenous administration the mean t½ was about 14 hr, volume of distribution about 3.0l/kg, and corrected renal clearance about 140 ml/min. An average of 35% of the dose was recovered unchanged in urine. After oral administration the absorption rate was rapid relative to the elimination rate, extent of bioavailability was complete, and the apparent volume of distribution was the same as that after intravenous injection. A dose regimen of 750 mg intravenously directly followed by 800 mg orally and subsequently 400 mg 3 times daily resulted in therapeutic plasma levels within 15 min. The plasma levels remained within the therapeutic range throughout a period of observation from 48 to 168 hr.Clinical Pharmacology and Therapeutics(1980)27,64–71; doi:10.1038/clpt.198

ISSN:0009-9236    

DOI:10.1038/clpt.1980.10

年代:1980

数据来源: WILEY