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Titolo:
Gender-related effects on metoprolol pharmacokinetics and pharmacodynamicsin healthy volunteers
Autore:
Luzier, AB; Killian, A; Wilton, JH; Wilson, MF; Forrest, A; Kazierad, DJ;
Indirizzi:
SUNY Buffalo, Sch Pharm, Buffalo, NY 14260 USA SUNY Buffalo Buffalo NY USA 14260 ffalo, Sch Pharm, Buffalo, NY 14260 USA SUNY Buffalo, Clin Pharmacokinet Lab, Buffalo, NY 14260 USA SUNY Buffalo Buffalo NY USA 14260 harmacokinet Lab, Buffalo, NY 14260 USA SUNY Buffalo, Millard Fillmore Hosp, Dept Med, Buffalo, NY 14260 USA SUNY Buffalo Buffalo NY USA 14260 e Hosp, Dept Med, Buffalo, NY 14260 USA
Titolo Testata:
CLINICAL PHARMACOLOGY & THERAPEUTICS
fascicolo: 6, volume: 66, anno: 1999,
pagine: 594 - 601
SICI:
0009-9236(199912)66:6<594:GEOMPA>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROPRANOLOL; METABOLISM; HYPERTENSION; CLEARANCE; TRIAL;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
19
Recensione:
Indirizzi per estratti:
Indirizzo: Luzier, AB SUNY Buffalo, Sch Pharm, 313 Cooke Hall, Buffalo, NY 14260 USA SUNY Buffalo 313 Cooke Hall Buffalo NY USA 14260 , NY 14260 USA
Citazione:
A.B. Luzier et al., "Gender-related effects on metoprolol pharmacokinetics and pharmacodynamicsin healthy volunteers", CLIN PHARM, 66(6), 1999, pp. 594-601

Abstract

Objective: To determine whether there are gender-specific differences in the pharmacokinetics and pharmacodynamics of metoprolol enantiomers. Methods: Twenty normal volunteers (10 men and 10 women) received 100 mg oral metoprolol tartrate twice daily for a total of nine doses. Pharmacokinetics and pharmacodynamics were studied after the last dose. Subjects also completed a control pharmacodynamic study; the order of drug and control studies was randomized. Measurements of heart rate and systolic blood pressure were obtained during peak submaximal bicycle exercise testing. (R)-Metoprolol and (S)-metoprolol concentrations were determined by stereospecific HPLC, The percentage difference in exercise heart rate and systolic blood pressure (metoprolol versus control), and (R)- and (S)-metoprolol plasma concentrations were comodeled,Results: Men and women showed stereoselective pharmacokinetics; (S)-metoprolol concentrations were significantly greater than those for (R)-metoprolol for both groups, Women had greater drug exposure than men (higher maximumconcentration and area under the plasma concentration-time curve), No differences were observed between genders with respect to elimination half-life, Females had a greater reduction in exercise heart rate and systolic bloodpressure; however, the area under the effect curve was significantly greater for heart rate only. Pharmacodynamic data were best fitted by the Kill equation with the effect site in the central compartment, The fitted maximumeffect and the concentration at one-half of the maximum effect for heart rate and systolic blood pressure did not differ between men and women (P > .20). Conclusions: Gender-related differences exist in the pharmacokinetics of metoprolol enantiomers, resulting in greater drug exposure in female subjects. However, concentration-effect relationships did not differ between men and women. Therefore the observed differences in drug effects were the result of gender-specific differences in metoprolol pharmacokinetics.

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Documento generato il 23/10/20 alle ore 11:56:28