RESUMO
The bioavailability of clopidogrel bisulfate (CAS 135046-48-9) form I was compared with that of clopidogrel bisulfate form II in 12 male Sprague-Dawley rats. The rats, randomly divided into two groups, received a single oral dose of 8 mg/kg clopidogrel (CP) bisulfate form I and form II, respectively, under fasting condition. The plasma concentrations of CP and its inactive carboxylic acid metabolite (CAS 144457-28-3, IM) were simultaneously determined by a sensitive, specific LC-MS/MS method. The pharmacokinetic parameters included C(max), T(max), t1/2, AUC(0-t), AUC(0-infinity). The AUC(0-infinity) of CP was 13.78 +/- 0.67 and 11.46 +/- 1.98 ng/ mL x h for CP form I and form II, respectively. The AUC(0-infinity) of IM was 33.08 +/- 5.76 and 21.67 +/- 8.95 microg/mL x h for CP form I and form II, respectively. The maximum plasma concentration (C(max)) of CP was 3.81 +/- 0.54 ng/mL for CP form I and 3.18 +/- 0.31 ng/mL for CP form II, the C(max) of IM was 3.42 +/- 0.41 and 2.08 +/- 0.68 microg/ mL for the CP form I and form II, respectively. There was an obvious difference between form I and form II for C(max) and the area under the plasma concentration time curve for both CP and IM after a t-test. This study shows that CP form I has better bioavailability in rats than CP form II.
Assuntos
Inibidores da Agregação Plaquetária/química , Inibidores da Agregação Plaquetária/farmacocinética , Ticlopidina/análogos & derivados , Animais , Área Sob a Curva , Atorvastatina , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão , Clopidogrel , Meia-Vida , Ácidos Heptanoicos/química , Ácidos Heptanoicos/farmacocinética , Inibidores de Hidroximetilglutaril-CoA Redutases/química , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacocinética , Masculino , Pirróis/química , Pirróis/farmacocinética , Ratos , Ratos Sprague-Dawley , Padrões de Referência , Reprodutibilidade dos Testes , Espectrometria de Massas por Ionização por Electrospray , Espectrofotometria Ultravioleta , Espectrometria de Massas em Tandem , Ticlopidina/química , Ticlopidina/farmacocinéticaRESUMO
AIM: To study the NMR phenomena of cetirizine hydrochloride and assign all proton and carbon signals in NMR spectra. METHODS: To record the 1D and 2D NMR spectra of cetirizine hydrochloride while changing the experimental temperature and adding D2O into the solution. RESULTS: More than one NMR signal or broad peak resulting from piperazine and the attached groups with N atom were given in DMSO-d6 solution at room temperature. "Coalescence" or narrowing had occurred for the proton and carbon signals when the experimental temperature was increased or D2O was added into the solution. CONCLUSION: Compared with the NMR "time scale", there are more than one conformation of cetirizine hydrochloride in DMSO-d6 solution at room temperature. The different conformation will be exchanged fast while temperature rise and the stable conformation will be existed while D2O was added into the solution.
