Pharmacokinetics of oxprenolol in normal subjects The effect of oxprenolol administered intravenously (10 and 20 mg) and orally (20, 40, 80, and 160 mg) on plasma concentrations of the drug, resting heart rate, exercise-induced tachycardia, and arterial blood pressure was assessed as a function of time in 6 healthy subjects. The pharmacokinetics of oxprenolol following intravenous administration are best described as 2-compartnent open model with dose-dependent parameters. The mean (±SD) plasma ha(f-life for oral doses is 1.94 ± 0.37 and for intravenous doses is 2.31 ± 0.64 hr. After oral administration, peak plasma concentrations are reached within 30 to 90 min, and the area under the plasma concentration-time curve varies linearly with the dose. Comparison of oral and intravenous data reveals the variation in bioavailabilty Qf orally administered oxprenolol to range from 19% to 74%. Unlike propranolol, oxprenolol does not show a saturable "first-pass" elimination effect. Blockade of f3-receptors occurs at plasma levels in excess of 60 ng /ml as evidenced by significant reductions in resting heart rate and exercise-induced tachycardia. Higher plasma concentrations of oxprenolol are required to lower blood pressure compared to those necessary to slow heart rate. These data suggest significant pharmacokinetic d(tferences between oxprenolol and other f3-adrenergic receptor allfagonists. William D. Mason, Ph.D., and Nathaniel Winer, M.D. Kansas City, Mo.

University Qf Missouri, Kansas City School Qf Medicine and School Qf Pharmacy

The pharmacokinetics and bioavailability of several ,B-adrenergic receptor blocking drugs (alprenolol, oxprenolol, pindolol, practolol, and propranolol) have recently been reviewed,12 and it is apparent that the pharmacokinetics of oxprenolol and the effect of presystemic hepatic elimination or "first-pass" effect on the bioavailability of this drug have not been adequately studied. In particular, definitive plasma concentration (C p ) against time (t) data following both intravenous and oral administration at several dose levels in Received for publication April 20, 1976. Accepted for publication July 7, 1976. Reprint requests to: William D. Mason, Ph.D., Biopharmacomet· ric Laboratory, Room M4-211, 2411 Holmes St., University of Missouri, Kansas City School of Medicine, Kansas City, Mo. 64108.

normal subjects has not been reported. Riess and associates,10 using tritium-labeled oxprenolol, indicated that oxprenolol absorption following oral administration exceeded 70% and that the drug was extensively metabolized prior to excretion. The plasma concentration data in this study were not sufficient for a detailed pharmacokinetic analysis. In a study in which oral doses of 40, 80, and 160 mg oxprenolo1 were administered as a single dose to 7 subjects, * bioavailability and half-life were determined as functions of dose. This report suggested that the bioavailability (as indicated by the area under the plasma concentration-time 'Jack, D. B., and Imhof, P.: Plasma levels following administration of 40,80, and 160 mg Transicor as single oral doses. (Personal communication. )

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Mason and Winer

Table I. Oxprenolol plasma concentration after 10 and 20 mg intravenously Plasma concentration * Min Subject! dose

A B

C D E

F

10 20 10 20 10 20 10 20 10 20 10 20

mg mg mg mg mg mg mg mg mg mg mg mg

10

240 504 234 454 298 610 288 482 278 561 271 554

Hr

I 25 I 40 190 440 185 369 223 447 224 331 220 430 192 356

164 341 160 312 186 355 170 270 153 320 136 277

1

143 284 122 241 135 275 125 214 116 227 99 185

I

2

97 213 48 88 74 152 82 138 45 102 57 126

I

3

67 142 28 57 48 94 28 70 34 65 44 99

I

AUC~t

4

47 95 21 43 34 65 20 49 22.7 48 34 77

I

6

22 47 11 23 17 30 8 20 9.9 21 19 47

I

ng . hr

8

ml