Cardiac and Pulmonary Effects of Acebutolol

Kumana, CR; Leighton, Monica; Kaye, C M; Turner, Paul; Hamer, John

doi:10.1016/s0140-6736(75)90001-x

Cited by 45 publications

(16 citation statements)

References 37 publications

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“…15 Since elimination appeared to become monoexponential soon after both oral and intravenous administration of acebutolol and the calculated elimination rate was of the same order at quite different plasma levels, the elimination characteristics of the parent drug and its metabolite are likely to be very similar and involvement of saturation kinetics improbable. Fig.…”

Section: Discussionmentioning

confidence: 99%

Observations on the pharmacokinetics of acebutolol

Kaye

Kumana

Leighton

et al. 1976

Clin Pharma and Therapeutics

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Using a balance, randomized, crossover design, single intravenous (1 mg/kg) or oral (3 X 100 mg) doses of acebutolol were administered at weekly intervals to 6 healthy volunteers. For each subject venous blood samples and timed urine collections were obtained after each treatment. Plasma and urinary acebutolol levels were measured by a spectrophotometric method that measures acebutolol and its N-acetyl metabolite (which has equivalent cardiac activity). Using a computer program, various pharmacokinetic parameters were estimated from the date of each subject. From the intravenous data (obtained up to 6 hr after dosing), the following mean (+/-SD) values were found: distribution half-life (T 1/2D), 0.60 (+/-0.43) hr, plasma elimination half-life (T 1/2El), 3.2 (+/-1.1) hr, apparent volume of distribution (VD), 224 (+/-69) L, and apparent VD/kg, 3.0 (+/-0.8) L/kg. Using the oral data (obtained up to 10 hr after dosing), the value for T 1/2El was 3.2 (+/-0.9) hr. The mean cumulative urinary recovery (expressed as % dose) after the intravenous route was about 60%, while that after the oral route was of the order of 35%, suggesting that about half of the oral dose reached the systemic circulation. The mean creatinine clearance of the 6 subjects was 103 (+/-7) ml/min, while the value (obtained between 2 and 4 hr after intravenous dosing) for renal clearance of acebutolol as measured was 298 (+/-68) ml/min and the corresponding plasma clearance was 818 (+/-64) ml/min. These results support the occurrence of substantial nonrenal elimination and renal tubular secretion.

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Section: Discussionmentioning

confidence: 99%

Observations on the pharmacokinetics of acebutolol

Kaye

Kumana

Leighton

et al. 1976

Clin Pharma and Therapeutics

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“…Acebutolol is a new,-adrenoceptor blocking agent effective in man (Lewis, Bakst, Kitchiner & Gotsman, 1973a;Cuthbert & Collins, 1975); Kumana, Kaye, Leighton, Turner & Hamer, 1975), which may be useful in the treatment of hypertension, angina pectoris (Lewis, Bakst, Kitchiner & Gotsman, 1973b;, and cardiac arrhythmias (Biron, Proulx, Lapointe, Nadeau & Tremblay, 1975). The use of 13-adrenoceptor blocking drugs in the control of hypertension is now well established, and it is therefore likely that this drug may be prescribed for patients who have hypertension associated with severe renal impairment.…”

Section: Preliminary Observations On the Elimination Of Acebutolol Inmentioning

confidence: 99%

Preliminary observations on the elimination of acebutolol in severe chronic renal failure [letter].

Kaye¹,

Dufton²

1976

Brit J Clinical Pharma

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“…The least effort dependent of these measurements, namely V50 (Bouhuys, 1974) gave rise to significant differences at rest, but not during exercise; much greater variation being evident during exercise. Previous reports had indicated that exercise was helpful in distinguishing between the selectivity of different drugs (Kumana, Marlin, Kaye & Smith, 1974;Kumana, Kaye, Leighton, Turner & Hamer, 1975) and it is of interest that in our study, only an exercise measurement, (Figure 2). Thus any differences between their effects on indices of airway function was likely to be pertinent with respect to relative 'selectivity'.…”

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confidence: 90%