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  • Title: Comparison of single-dose pharmacokinetic and pharmacodynamic properties of two metoprolol Oros systems with different initial zero-order release rates.
    Author: Warrington SJ, Barclay SP, John VA, Shotton PA, Good W.
    Journal: Br J Clin Pharmacol; 1985; 19 Suppl 2(Suppl 2):225S-230S. PubMed ID: 4005127.
    Abstract:
    Plasma concentrations and haemodynamic effects at rest and during exercise have been measured in six healthy volunteers after single oral dosing with two Oros drug delivery systems containing 190 mg metoprolol fumarate but with initial release rates of 14 and 19 mg/h, respectively. Sub-maximal exercise heart rates were attenuated by both Oros systems throughout most of the 30 h study period but no significant differences were detected between the 14/190 and 19/190 forms. Resting pulse rates and blood pressure were similarly affected by the Oros preparations. Approximately the same amount of drug reached the circulation from the Oros systems, but the 19/190 form produced higher peak concentrations at earlier times after dosing. At 24 h higher plasma concentrations were observed for the 14/190 preparation, reflecting its longer duration of drug release. There was no apparent advantage of one form over the other as regards haemodynamic response. The reduced peak plasma concentration with 14/190 Oros may, however, be an advantage in terms of tolerability.
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