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Titolo:
THE PHARMACODYNAMICS AND PHARMACOKINETICS OF THE 5HT(1B 1D)-AGONIST ZOLMITRIPTAN IN HEALTHY-YOUNG AND ELDERLY MEN AND WOMEN/
Autore:
PECK RW; SEABER EJ; DIXON RM; LAYTON GR; WEATHERLEY BC; JACKSON SHD; ROLAN PE; POSNER J;
Indirizzi:
GLAXO WELLCOME RES & DEV LTD,GREENFORD RD GREENFORD UB6 0HE MIDDX ENGLAND UNIV LONDON KINGS COLL,SCH MED,DEPT HLTH CARE ELDERLY LONDON WC2R 2LSENGLAND
Titolo Testata:
Clinical pharmacology and therapeutics
fascicolo: 3, volume: 63, anno: 1998,
pagine: 342 - 353
SICI:
0009-9236(1998)63:3<342:TPAPOT>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
RECEPTOR AGONIST; SUMATRIPTAN; MIGRAINE; AGE; PROPRANOLOL; INHIBITION; VOLUNTEERS; 311C90;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
31
Recensione:
Indirizzi per estratti:
Citazione:
R.W. Peck et al., "THE PHARMACODYNAMICS AND PHARMACOKINETICS OF THE 5HT(1B 1D)-AGONIST ZOLMITRIPTAN IN HEALTHY-YOUNG AND ELDERLY MEN AND WOMEN/", Clinical pharmacology and therapeutics, 63(3), 1998, pp. 342-353

Abstract

Objective: Zolmitriptan is a selective 5HT(1B/1D)-agonist for the treatment of migraine. In this study we investigated the cardiovascular and central nervous system effects and the pharmacokinetics of zolmitriptan in young and elderly adults. Methods: Twelve young adult and 12 elderly volunteers received single doses of 5, 10, and 15 mg zolmitriptan during a randomizd, double-blind, placebo-controlled study. Blood pressure, heart rate, ECG, and central nervous system effects were monitored, and pharmacokinetic parameters of zolmitriptan and its metabolites calculated. Results: Zolmitriptan did not affect heart rate and had little effect on systolic blood pressure in the young adults. In theelderly, mean peak supine systolic blood pressure values were 9 to 16mm Hg higher after zolmitriptan than after placebo. Mean peak diastolic pressure was 6 to 10 mm Hg higher in both age groups. These changeswere transient. Postural changes in blood pressure were unaffected. These was a dose-related increase in sedation, but the magnitude of theeffects was small. Mean observed peak plasma concentration (C-max) and area under the plasma concentration-time profile [AUC-(0-infinity)] for zolmitriptan and its active N-desmethyl metabolite were similar inboth age groups but higher in young women than in young men. Metabolite/parent ratios were higher in young men, No such differences were apparent in the elderly. The gender-related difference is probably the result of greater first-pass metabolism in young men. Zolmitriptan half-life was 2.8 to 3.6 hours in the elderly compared with 2.7 to 2.9 hours in young adults. Mean C-max and AUC(0-infinity) for the inactive, N-oxide, and the indole acetic acid metabolites were higher in the elderly, associated with lower renal clearance Conclusions: Zolmitriptan was well tolerated, with an effect of age on its effects on blood pressure and the pharmacokinetics of its metabolites. The data suggest no need for dose adjustment for age. In young subjects, concentrations were higher in women than in men, but the difference were insufficient tojustify dosage adjustment.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/12/20 alle ore 21:42:19