The effect of oxprenolol dosage time on its pharmacokinetics and haemodynamic effects during exercise in man

We have studied the effect of dosage time of oxprenolol (Trasicor) on its pharmacokinetics and pharmacodynamics in six healthy volunteers. The drug effects measured were heart rate and systolic blood pressure during exercise. Oxprenolol was taken orally at 08.00 h, 14.00 h, 20.00 h, and 02.00 h in r...

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Published inEuropean journal of clinical pharmacology Vol. 44; no. 2; p. 171
Main Authors Koopmans, R, Oosterhuis, B, Karemaker, J M, Wemer, J, van Boxtel, C J
Format Journal Article
LanguageEnglish
Published Germany 01.03.1993
Subjects
Adult
Blood Pressure - drug effects
Blood Pressure Determination
Circadian Rhythm - drug effects
Exercise - physiology
Half-Life
Heart Rate - drug effects
Hemodynamics - drug effects
Humans
Male
Oxprenolol - administration & dosage
Oxprenolol - pharmacokinetics
Oxprenolol - pharmacology
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Summary:We have studied the effect of dosage time of oxprenolol (Trasicor) on its pharmacokinetics and pharmacodynamics in six healthy volunteers. The drug effects measured were heart rate and systolic blood pressure during exercise. Oxprenolol was taken orally at 08.00 h, 14.00 h, 20.00 h, and 02.00 h in randomized order, with 1 week between successive doses. There were differences in the pharmacokinetics of oxprenolol for the ratio between the apparent volume of distribution and systemic availability (P = 0.04) and for elimination half-life (P = 0.006). Both were lowest after administration at 14.00 h (163 (77) l and 1.2 (0.6) h; mean (SD)) and highest after administration at 02.00 h (229 (100) l, and 1.7 (0.6) h). The systolic blood pressure during exercise before oxprenolol did not vary with dosage time, but heart rate during exercise before intake was lowest before dosage time 08.00 h and highest before dosage time 20.00 h (P = 0.03). The time-course of heart rate during exercise after oxprenolol was described by a model that incorporated the factors drug concentration and spontaneous diurnal variation. EC50 and Emax did not vary between dosage times. The spontaneous diurnal variation in heart rate during exercise was unaffected by oxprenolol, leading to an apparently greater effect of oxprenolol during the night than during the day.
ISSN:0031-6970
DOI:10.1007/BF00315476