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Titolo:
Pharmacokinetics of dihydrocodeine and its active metabolite after single and multiple oral dosing
Autore:
Ammon, S; Hofmann, U; Griese, EU; Gugeler, N; Mikus, G;
Indirizzi:
Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-70341 Stuttgart, GermanyDr Margarete Fischer Bosch Inst Clin Pharmacol Stuttgart Germany D-70341
Titolo Testata:
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
fascicolo: 3, volume: 48, anno: 1999,
pagine: 317 - 322
SICI:
0306-5251(199909)48:3<317:PODAIA>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
POOR METABOLIZERS; O-DEMETHYLATION; HUMAN-LIVER; CODEINE; DEBRISOQUINE; CYP2D6; DIHYDROMORPHINE; SPARTEINE; MORPHINE;
Keywords:
dihydrocodeine; dihydromorphine; multiple dose; pharmacokinetics; single dose;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
20
Recensione:
Indirizzi per estratti:
Indirizzo: Ammon, S Dr Margarete Fischer Bosch Inst Clin Pharmacol, PO Box 501120, D-70341 Stuttgart, Germany Dr Margarete Fischer Bosch Inst Clin Pharmacol PO Box 501120 Stuttgart Germany D-70341
Citazione:
S. Ammon et al., "Pharmacokinetics of dihydrocodeine and its active metabolite after single and multiple oral dosing", BR J CL PH, 48(3), 1999, pp. 317-322

Abstract

Aims The pharmacokinetics of dihydrocodeine (DHC) and its active metabolite dihydromorphine (DHM) were assessed after a single oral dose of DHC and after increasing doses of DHC at steady-state. Methods Twelve healthy male volunteers (18-45 years, CYP2D6 extensive metabolizers (EMs), MR<1 took a single oral dose (s.d.) of DHC 60 mg after breakfast. After 60 h DHC 60 mg was administered twice daily for 3 days, the dose was increased to 90 mg twice daily for 3 days, the final dose of 120 mg was administered twice daily for 3 days (multiple dose: m.d.). Blood sampling and urine collection: during 60 h after s.d. and during 12 h after m.d. Results No significant differences in the area under the curve (AUC) of both, DHC and DHM could be detected after a single oral dose of 60 mg DHC (AUC (0,infinity)) and during steady-state doses of 60 mg DHC (AUC(0,12 h)). During increasing steady-state doses of DHC, the data showed a dose linearity of AUG, maximal serum concentration (C-max) and minimal steady-state serum levels (C(ss)min) of both, DHC and DHM (P<0.0001), point estimates of DHCdose corrected AUCs were well within the bioequivalence range (60 mg: 0.989; 90%CI 0.951-1.028, 90 mg: 0.997; 90%CI 0.959-1.036, 120 mg: 0.977; 90%CI0.940-1.016). O-demethylation from DHC to DHM remained constant within theincreasing steady-state doses of DHC in the 12 extensive metabolizers of CYP2D6. Conclusions In the studied dose range (60-120 mg) the pharmacokinetics of DHC and its active metabolite DHM are linear in EMs of CYP2D6.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 18/01/20 alle ore 10:43:16