Ro 3–4787, A NEW β‐ADRENOCEPTOR BLOCKING AGENT: STUDIES IN NORMAL VOLUNTEERS

Kilborn, J. R.; Turner, Paul

doi:10.1111/j.1365-2125.1974.tb00223.x

Cited by 10 publications

(4 citation statements)

References 6 publications

(9 reference statements)

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“…A previous study which compared the (Fothergill et al, 1975) which possesses partial effects of intravenous bufuralol and propranolol agonist activity at the 13-adrenoceptor (Hamilin volunteers showed that the two drugs had ton & Parkes, 1977). Although, partial agonist similar potency in decreasing an exercise tachyactivity is of questionable therapeutic importance cardia (Kilborn & Turner, 1974). In this study, (McDevitt, 1983) bufuralol has been found to we have compared the effects of five oral doses Correspondence: Professor R. G. Shanks of bufuralol and two doses of propranolol and placebo on heart rate and blood pressure in healthy subjects.…”

Section: Introductionmentioning

confidence: 90%

Pharmacodynamic and pharmacokinetic studies on bufuralol in man.

Pringle¹,

Francis²,

East³

et al. 1986

Brit J Clinical Pharma

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1 Observations were made in eight subjects who exercised before and at 1, 2, 4, 6, 8 and 24 h after the double-blind oral administration of placebo, bufuralol 7.5, 15, 30, 60 and 120 mg and propranolol 40 and 160 mg. 2 The exercise heart rate remained constant after placebo. Bufuralol 7.5 mg and propranolol 40 mg reduced exercise heart rate up to 6 and 8 h respectively after dosing but bufuralol 15, 30, 60 and 120 mg and propranolol 160 mg were still active at 24 h. 3 The lowest exercise heart rate occurred at 2 h after all active treatments. Bufuralol 60 and 120 mg produced similar reduction in exercise tachycardia as propranolol 40 mg but less than propranolol 160 mg. 4 Plasma levels of bufuralol and its two major metabolites were measured. The peak plasma concentrations of bufuralol occurred at 1.5 h after 7.5 mg and at 2 h after the other doses of bufuralol. In six subjects the plasma elimination half-life of bufuralol was 2.61 + 0.18 h and in the other three subjects 4.85 ± 0.35 h. There was a corresponding longer time to peak concentration and plasma elimination half-life of the two metabolites in these three subjects. 5 These findings show that bufuralol is a potent ,B-adrenoceptor antagonist with partial agonist activity. It has a long duration of action and there is bimodal metabolism of the drug in man.

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Section: Introductionmentioning

confidence: 90%

Pharmacodynamic and pharmacokinetic studies on bufuralol in man.

Pringle¹,

Francis²,

East³

et al. 1986

Brit J Clinical Pharma

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“…An ortho relationship for the aromatic oxygen substituents was considered most likely because of the probable formation of this compound from the corresponding catechol by the action of catechol O-methyltransferase (17). MIO (m/e 453) was identified as the phenolicmethoxyaIcohol (+ 20H + OMe + [2][3][4][5] corresponding to the Ml2 ketone since its gc retention time was identical to that of the deuterated compound (m/e 454) produced on borodeuteride reduction of the latter.…”

Section: Metabolites Extracted At Basic Phmentioning

confidence: 99%

“…The chemistry (2) and pharmacology (3) of the compound have been described elsewhere, as well as clinical observations in normal volunteers (4) and hypertensive patients (5). A spectrofluorimetric analytical method also has been reported (6).…”

Section: Introductionmentioning

confidence: 99%

The metabolism of bufuralol: Urinary metabolite profiles in rat, dog and man

Francis

Allen

East

et al. 1976

European Journal of Drug Metabolism and Pharmacokinetics

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The metabolism of a new~-adrenoceptor blocking agent, bufuralol, 7-ethyl-iX[(tertiary butylamino)-methylj-2-benzofuran methanol. HCI, was studied in rat, dog and man. After oral administration of the labelled drug, 34 % of dose was eliminated in urine by the rat, 50 % by the dog, and 75 %by man. Examination of urine extracts by gas chromatographymass spectrometry with single-and multiple-ion monitoring indicated the presence of twelve metabolites. These were identified as mono-, di-and tri-oxygenated analogues of the parent drug. They had been formed from four main pathways, two involving aliphatic and two aromatic hydroxylation. All but one were present partly in conjugated and partly in free form. Three further metabolites were detected in dog urine. Two were conjugates with an unidentified hexuronic acid moiety, the third the hydroxy-acid resulting from degradation of the~-hydroxyamine side-chain of the parent drug.

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“…First studies in man have shown that bufuralol has a longer duration of action and a greater potency than propranolol (Kilborn & Turner, 1974;Tschopp et al, 1978). This lipophilic compound is metabolised by the liver and three metabolites of bufuralol have been identified in human plasma: an alcoholic or carbinol derivative (1'-hydroxybufuralol), a phenol derivative (4-hydroxybufuralol) and a ketone derivative (Francis et al, 1976;Balant et al, 1980).…”

Section: Defective Hydroxylation Of Bufuralol Associated With Side-efmentioning

confidence: 99%