Lack of correlation between acetylator status and the production of the acetyl metabolite of acebutolol in man.

Gulaid, A.A.; Im, James; Kaye, C M; Lewellen, OR; Roberts, Elizabeth S.; Sankey, M. G.; Smith, Jordan N.; Templeton, R. D.; Thomas, R. J.

doi:10.1111/j.1365-2125.1978.tb01634.x

Cited by 27 publications

(3 citation statements)

References 10 publications

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“…Since the metabolite (diacetolol) persists in the circulation longer than the parent drug (acebutolol) (Meffin et al, 1976(Meffin et al, , 1978Winkle et al, 1977), it is possible that diacetolol may make a major contribution to the long 'pharmacological' half-life of oral acebutolol that has been observed in man (Martin et al, 1978;Watson & Littler, 1979). It has been previously shown in man that the metabolic production of diacetolol from acebutolol is not under genetic control (Gulaid et al, 1978). The results of this study strongly suggest that the metabolic conversion of acebutolol to diacetolol is not responsible for any inter-patient variation seen in the clinical response to oral acebutolol, since the parent drug and its metabolite have a similar spectrum of pharmacological activity in man.…”

Section: Discussionsupporting

confidence: 50%

Observations on the clinical pharmacology and plasma concentrations of diacetolol, the major human metabolite of acebutolol.

Ohashi¹,

Warrington²,

Kaye³

et al. 1981

Brit J Clinical Pharma

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1 The pharmacological effects and plasma levels of diacetolol, the major human metabolite of acebutolol, were measured in a double-blind, balanced study in which five healthy men received single oral doses of diacetolol 100, 200, 400 and 800 mg, or placebo, at weekly intervals.2 Resting and exercise heart rate (HR), forced expiratory volume in 1 second (FEVy), resting and exercise peak expiratory flow rate (PEFR), and plasma concentrations of diacetolol were determined at 0, 2, 4, 6, 8 and 24 h after each treatment. 3 Diacetolol caused a slight dose-related reduction in resting HR and a substantial dose-related reduction in exercise HR. At the same time it was found that diacetolol had no significant effects on FEV, and resting and exercise PEFR. 4 Mean highest observed plasma concentrations (ng/ml) of diacetolol were 177 at a mean of 4.4 h after the 100 mg dose, 243 at 4.0 h after the 200 mg dose, 807 at 5.2 h after the 400 mg dose, and 1,306 at 4.4 h after the 800 mg dose. 5 Using the mean data, there was a strong correlation (r = 0.90) between % reduction in exercise HR and the logarithm of the plasma concentration of diacetolol. 6 Diacetolol exhibits marked cardiac -adrenoceptor blocking activity in man which is still evident 24 h after the administration of the higher doses of the drug. No adverse effects on pulmonary function could be detected.

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Section: Discussionsupporting

confidence: 50%

Observations on the clinical pharmacology and plasma concentrations of diacetolol, the major human metabolite of acebutolol.

Ohashi¹,

Warrington²,

Kaye³

et al. 1981

Brit J Clinical Pharma

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“…For instance hydralazine-induced lupus reactions supervene more frequently in slow acetylators of the drug (Perry et al, 1970). However a report from Gulaid et al (1978) suggests that the overall process of acetyl metabolite production from acebutolol in man does not appear to be under genetic control. Preliminary studies in animals and in man of the acetyl metabolite of acebutolol, diacetolol (Flouvat et al, 1981a) suggest that this drug is pharmacologically active, possesses 83-adrenoceptor antagonist properties and acts with relative cardioselectivity.…”

Section: Discussionmentioning

confidence: 99%

Antihypertensive effect of diacetolol in essential hypertension.

Thibonnier¹,

Flabeau²,

Thouvenin³

et al. 1982

Brit J Clinical Pharma

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1 Diacetolol is the N‐acetylated metabolite of acebutolol and possesses beta‐adrenergic receptor blocking properties. 2 Its antihypertensive action was assessed in accordance with a double‐blind randomised cross‐ over scheme in 17 patients with moderate essential hypertension previously well controlled with acebutolol. 3 Significant reductions in lying mean arterial blood pressure were observed with daily doses of 200 mg (‐ 9%), 400 mg (‐ 10%) and 800 mg (‐ 14%), and were associated with significant decreases in heart rate and plasma renin activity. 4 The diacetolol mean plasma level measured 8 to 10 h after drug ingestion was proportional to the dose (207 +/‐ 27, 394 +/‐ 63 and 823 +/‐ 135 ng/ml for respectively 200, 400 and 800 mg/day).

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“…It should be noted, however, that not every drug that is acetylated will display a polymorphism (e.g. acebutolol) (69).…”

Section: Generic Factorsmentioning

confidence: 99%

Factors Contributing to Variability in Drug Pharmacokinetics. Iii. Metabolism

Jack

2008

Journal of Clinical Pharmacy and Therapeutics

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Lack of correlation between acetylator status and the production of the acetyl metabolite of acebutolol in man.

Cited by 27 publications

References 10 publications

Observations on the clinical pharmacology and plasma concentrations of diacetolol, the major human metabolite of acebutolol.

Observations on the clinical pharmacology and plasma concentrations of diacetolol, the major human metabolite of acebutolol.

Antihypertensive effect of diacetolol in essential hypertension.

Factors Contributing to Variability in Drug Pharmacokinetics. Iii. Metabolism

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