Observations on the pharmacokinetics of acebutolol

Abstract

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.

Multi-functional scaling methodology for translational pharmacokinetic and pharmacodynamic applications using integrated microphysiological systems (MPS)

“…The test set of five drugs used in the multi-functional scaling approach to evaluate the resulting design parameters for multi-MPS platform I included: acetaminophen 45 , clozapine 46 , imipramine 47 , oxazepam 48 and sildenafil 49 ; for multi-MPS platform II: acebutolol 50 , alprazolam 51 , indomethacin 52 , ketoprofen 53 and nadolol 54 . References indicate source of time-concentration profiles and administered dose.…”

Acebutolol metabolite plasma concentration during chronic oral therapy.

“…Several recent studies have provided data on the plasma concentration of acebutolol (Gibbons, Lant, Ashford, Collins & Pinder, 1976; Kaye, Kumana, Leighton, Hamer & Turner, 1976;Kumana, Leighton, Kaye, Turner & Hamer, 1975; Kaye & Long, 1976;Kaye & Dufton, 1976;Roux, Flouvat & Delaveau, 1975;Collins, 1975). These studies, however, use non-specific methods of assay which measure acebutolol and potential metabolites as a single species.…”

“…Treatment with the ,B-adrenoceptor-blocking drug acebutolol is effective for a variety of cardiac conditions (Lewis, Bakst, Kitchiner & Gotsman, 1973;Ricks, Harrison, Bell & Winkle, 1976;Lewis, Mitna & Gotsman, 1974;Biron, Proulx, Lapointe, Nadeau & Tremblay, 1975). Several recent studies have provided data on the plasma concentration of acebutolol (Gibbons, Lant, Ashford, Collins & Pinder, 1976; Kaye, Kumana, Leighton, Hamer & Turner, 1976; Kumana, Leighton, Kaye, Turner & Hamer, 1975;Kaye & Long, 1976;Kaye & Dufton, 1976;Roux, Flouvat & Delaveau, 1975;Collins, 1975). These studies, however, use non-specific methods of assay which measure acebutolol and potential metabolites as a single species.…”

Acebutolol saliva excretion.

“…For example theoretical S/P ratio for propranolol can change in a 30-fold range when saliva pH varies in the physiologic range from 6.5 to 8. Recently, Kaye et al (1977) reported a S/P ratio of0.815 for acebutolol but on the one hand no saliva pH values were given and on the other hand the analytical method used (Kaye, Kumana, Leighton, Hamer & Turner, 1976) was not specific, detecting not only acebutolol but also its metabolites, including the acetyl analogue.…”