ISSN:
0899-0042
Keywords:
atenolol
;
enantiomers
;
pharmacokinetics
;
Chemistry
;
Organic Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
The purpose of this study was to describe the pharmacokinetics of and heart rate and blood pressure responses to (S)-atenolol (SATN) and (R)-atenolol (RATN) after oral administration of (S)-atenolol and (R,S)-atenolol (Tenormin™) in man. Eight male subjects were given single oral doses of 50 mg of SATN as a single enantiomer formulation (SEF) and 100 mg of Tenormin™ (TMN) using a randomized, double-blind, 2-period, complete crossover study design. Subjects performed exercise tolerance tests (Bruce Protocol) before and 2, 4, 6, 8, 12, and 24 h after drug administration. Plasma samples were obtained 2 min before and 30 min, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 h after dosing. Urine was collected for the first 48 h after dosing. Plasma and urine samples were analyzed for SATN and RATN by an enantioselective HPLC method. SEF and Tenormin™ attenuated exercise-induced increases in heart rate and systolic blood pressure. Mean changes in exercise heart rates 4 h after dosing were -38 ± 3 bpm and -37 ± 3 bpm for SEF and TMN, respectively, P = 0.792. Mean changes in exercise systolic blood pressure were -42 ± 12 mm Hg and -55 ± 14 mm Hg for SEF and TMN, respectively, P = 0.484. Mean area under the plasma level time curve (AUC0-24) and mean Cmax for SATN for SEF were significantly lower than for SATN after TMN. Mean SATN AUCs0-24 were 1867 ± 261 and 2543 ± 223 ng · h/ml (P = 0.005) and mean Cmaxs were 225 ± 29 and 333 ± 30 ng/ml, for SEF and TMN, respectively (P = 0.011). Mean Tmax for SATN occurred significantly earlier after SEF than after TMN (2.9 ± 0.3 and 3.3 ± 0.3 h, P = 0.028). The amount of SATN excreted in urine was significantly lower after SEF than after TMN (18.7 ± 2.7 and 24.2 ± 2.0 mg, P = 0.017). AUC, Cmax, and amount excreted in urine (Au) were significantly higher for RATN than SATN after TMN. Mean AUCs, Cmaxs, and Aus for RATN compared to SATN were 2806 ± 239 vs 2543 ± 223 ng ± h/ml (P 〈 0.0001), 360 ± 31 vs 333 ± 30 ng/ml (P 〈 0.0001), and 25 ± 2.1 vs 24 ± 2 mg (P = 0.004), respectively. SEF and TMN are equieffective in attenuating exercise-induced increases in heart rate and systolic blood pressure. The SEF has lower bioavailability compared to TMN and RATN plasma levels are higher than SATN after TMN administration. © 1994 Wiley-Liss, Inc.
Additional Material:
2 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/chir.530060303
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