Absolute bioavailability and dose proportionality of betaxolol in normal healthy subjects

T. M. Ludden, D. A. Boyle, D. Gieseker, G. T. Kennedy, M. H. Crawford, L. K. Ludden, W. A. Clementi

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Abstract

The absolute bioavailability and dose proportionality of betaxolol ((±)‐1‐(p‐[2‐cyclopropylmethoxy)ethyl[phenoxy]‐3‐(isopropylamino)‐2‐propanol hydrochloride], a cardioselective beta‐adrenergic antagonist effective in the treatment of angina and hypertension, was studied in 12 healthy male subjects using a four‐way crossover Latin Square design. Each subject received a 10‐mg iv dose administered by constant‐rate infusion over a period of 30 min and three oral doses (10, 20, and 40 mg). Blood and urine were collected over a 48‐h period and analyzed for betaxolol using gas–liquid chromatography with electron capture detection. Maximum concentrations occurred 3–4 h after the dose. The maximum mean (±SD) blood concentrations normalized to the 10‐mg oral dose were 21.6 ± 3.7, 21.1 ± 3.7, and 22.5 ± 4.0 μg/L following the 10‐, 20‐, and 40‐mg doses, respectively. A significant lag time of 10–80 min was observed after oral doses but was not related to dose size. The terminal slope (ts), absolute bioavailability (F), and renal clearance (CLr) were likewise not affected to an important degree by dose (ts: 0.043 ± 0.006, 0.044 ± 0.005, 0.046 ± 0.006 h−1; F: 0.88 ± 0.08, 0.82 ± 0.06, 0.84 ± 0.07; CLr: 0.68 ± 0.22, 0.69 ± 0.19, 0.65 ± 0.22 mL/min kg). Unlike many beta‐adrenergic antagonists, betaxolol has a long half‐life (13–20 h) and high and consistent bioavailability (70–90%), and its disposition is independent of the size of the administered dose.

Original languageEnglish (US)
Pages (from-to)779-783
Number of pages5
JournalJournal of Pharmaceutical Sciences
Volume77
Issue number9
DOIs
StatePublished - Sep 1988

ASJC Scopus subject areas

  • Pharmaceutical Science

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    Ludden, T. M., Boyle, D. A., Gieseker, D., Kennedy, G. T., Crawford, M. H., Ludden, L. K., & Clementi, W. A. (1988). Absolute bioavailability and dose proportionality of betaxolol in normal healthy subjects. Journal of Pharmaceutical Sciences, 77(9), 779-783. https://doi.org/10.1002/jps.2600770913