PubMed · 3892259
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1985-07-05. Acebutolol.. https://pubmed.ncbi.nlm.nih.gov/3892259/
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Acebutolol (AC) is a chiral beta-adrenergic receptor-blocking agent, which has been shown to be clinically effective in hypertension. The plasma concentration-time profiles of AC exhibit two peaks following oral administration of racemate for both R- and S-enantiomers. In the present study, the absorption of AC after a single dose was studied as a function of gastric pH in male Sprague-Dawley rats. Furthermore, the effect of cimetidine (CIM) on pharmacokinetic parameters of AC and its metabolite diacetolol (DC) was evaluated. CIM (50 mg kg(-1)) was administered via jugular vein 30 min prior to AC administration to elevate the intragastric pH. AC (50 mg kg(-1)) was administered orally by gavage and serial blood samples were collected before and for 8h after AC administration. Plasma samples were assayed for AC and DC, pharmacokinetic parameters were estimated and compared with those of control. The concentration-time profiles and the pharmacokinetics of AC were unchanged after co-administration of CIM. The oral absorption of AC, as assessed by the area under the plasma concentration-time curve (AUC) and the amount of unchanged drug recovered in the urine were not affected by CIM. The amount of metabolite recovered in the urine and the rate of absorption, however, were significantly altered. These are unlikely to be of clinically importance as we have found that the extent of absorption was not changed. We, therefore, concluded that intragastric elevation of pH has no effect either on generation of multiple peaking or on pharmacokinetic parameters of AC.
Because physiological changes that potentially alter pharmacokinetics occurs in diabetes mellitus patients, pharamacokinetics of drugs used in the treatment of hypertension was studied using acebutolol as a model anti-hypertensive drug. Thus, the pharmacokinetics of acebutolol was investigated after oral administration of acebutolol (15 mg/kg) to control rabbits and rabbits with acute or chronic diabetes mellitus induced by alloxan. Kidney and liver functions were documented for acute and chronic diabetes mellitus groups based on plasma chemistry data. After oral administration of acebutolol to acute and chronic groups, the plasma concentrations appeared higher; As a result, area under the plasma concentration-time curve from time zero to time infinity10575 and 8668 microg x h/mL for acute and chronic group, respectively. In comparison, the area was apparently smaller in the control group (i.e., 7132 microg x h/mL). The half-life in acute groups was significantly prolonged 8.45 h compared with the half-life in the control group (i.e., 6.30 h). Alteration in acebutolol pharmacokinetics was more pronounced in the acute group as evidenced by the significantly higher values the area under the plasma concentration time curve, absorption rate constant and maximum plasma concentration compared with chronic or control group. Therefore, these observations indicate that acebutolol pharmacokinetics may be affected in patients with diabetes mellitus, especially in the early stage of the disease.
BACKGROUND: Hypertension is a major health problem in both developed and developing countries. It is hypothesized that high blood pressure is associated with loss of balance between peroxidation and antioxidant factors. MATERIAL/METHODS: 40 patients with essential hypertension were studied to ascertain the effects of a selective b1-blocker (acebutolol, 400 mg/day) on serum lipids, antioxidant status, antioxidant enzyme activity in red blood cells (RBC), and membrane fatty acids composition. Each subject was screened by physical examination, ECG, echocardiography, and laboratory tests. The period of observation was 24 weeks, and the data were tested by 2-way ANOVA followed by Bartlett's least significant difference test. RESULTS: At 12 weeks, serum triacylglycerol was more elevated (+26%). At 24 weeks, apolipoprotein A-1 levels remained more elevated (+41%) in hypertensive subjects compared to controls. In hypertensive patients, total antioxidant status and total plasma antioxidant capability were lower at 12 weeks than controls, and increased after 24 weeks of treatment. At 12 weeks, superoxide dismutase, catalase and glutathione reductase activities in erythrocytes remained lower in hypertensive subjects compared to controls (-32%, -40% and -24%, respectively). At 24 weeks, these values were increased compared to those obtained at 12 weeks (+26%, +36% and +37%, respectively). At 12 and 24-weeks, total n-3 and n-6 fatty acids were decreased by 26%, 18% and 29%, 25%, respectively. CONCLUSIONS: These findings demonstrate the beneficial influence of a beta1-blocker (acebutolol) at 24 weeks by its action on serum lipids, antioxidant status and RBC antioxidant enzyme activities.