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Titolo:
A double-peak phenomenon in the pharmacokinetics of alprazolam after oral administration
Autore:
Wang, YX; Roy, A; Sun, L; Lau, CE;
Indirizzi:
Rutgers State Univ, Dept Psychol, Piscataway, NJ 08854 USA Rutgers State Univ Piscataway NJ USA 08854 chol, Piscataway, NJ 08854 USA Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Environm & Occupat Hlth Sci Inst, Piscataway, NJ 08854 USA Univ Med & Dent New Jersey Piscataway NJ USA 08854 scataway, NJ 08854 USA Rutgers State Univ, Dept Chem, Piscataway, NJ 08854 USA Rutgers State Univ Piscataway NJ USA 08854 Chem, Piscataway, NJ 08854 USA
Titolo Testata:
DRUG METABOLISM AND DISPOSITION
fascicolo: 8, volume: 27, anno: 1999,
pagine: 855 - 859
SICI:
0090-9556(199908)27:8<855:ADPITP>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
RELATING DRL PERFORMANCE; DIFFERENTIAL REINFORCEMENT; INDEPENDENT INTERACTION; NEWER BENZODIAZEPINES; CAFFEINE; METABOLITES; ABSORPTION; MIDAZOLAM; EFFICACY; RATS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
24
Recensione:
Indirizzi per estratti:
Indirizzo: Lau, CE Rutgers State Univ, Dept Psychol, 152 Frelinghuysen Rd, Piscataway, NJ 08854 USA Rutgers State Univ 152 Frelinghuysen Rd Piscataway NJ USA 08854 SA
Citazione:
Y.X. Wang et al., "A double-peak phenomenon in the pharmacokinetics of alprazolam after oral administration", DRUG META D, 27(8), 1999, pp. 855-859

Abstract

The pharmacokinetics of alprazolam (ALP) after i.v. and p.o. administration in rats were characterized. ALP decayed biexponentially after the i.v, dose (1.25 mg/kg), but the concentration-time profiles after the p.o. doses (7 and 12.5 mg/kg) exhibited a double-peak phenomenon. The presence of two peaks was confirmed by statistical analysis of the serum concentration data of ALP, as well as by observed double peaks in the serum concentration-timeprofiles of the two active metabolites (alpha-hydroxyalprazolam and 4-hydroxyalprazolam). An absorption model incorporating a delay site is proposed to describe the data, and the absolute oral bioavailability is estimated tobe about 30%, The two peaks were similar to 80 to 115 min apart, and therewas a delay in the absorption of close to 80% of oral ALP, regardless of dose, We hypothesize that the mechanism underlying the double-peak phenomenon is due to reduction in gastric motility caused by the muscle relaxant effect of ALP, This hypothesis is supported by the observed longer delay in the appearance of the second peak at the higher p.o. dose, Enterohepatic recycling is precluded from being the underlying mechanism, because of the presence of double peaks after the p.o. doses but not after the i.v. dose, Thisis the first reported case of double peaks for oral ALP, and this phenomenon has not been reported for other benzodiazepines, The double-peak phenomenon caused by the hypothesized mechanism may have important therapeutic anddrug interaction implications, especially because benzodiazepines are commonly coadministered with other drugs.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/04/20 alle ore 01:29:51