Studies on differences of pharmacokinetic behavior and tissue distribution of nimodipine and its two enantiomers in rats using achiral and chiral liquid chromatography / 药学学报
Acta Pharmaceutica Sinica
;
(12): 603-608, 2003.
Artigo
em Inglês
| WPRIM
| ID: wpr-266627
ABSTRACT
<p><b>AIM</b>To investigate the differences of pharmacokinetic behavior and tissue distribution of nimodipine and its two enantiomers in rats.</p><p><b>METHODS</b>A high-performance liquid chromatographic method with an ODS column (150 mm x 4.6 mm ID) and a mobile phase of methanol-water (7030) was used for racemic nimodipine assay. Another method with a Chiralcel OJ column (250 mm x 4.6 mm ID) and a mixture of n-haxane-ethanol (8515) as mobile phase was used to determine its two enantiomers. Nimodipine was monitored at 236 nm wavelength.</p><p><b>RESULTS</b>The linearity, recoveries and the detection limits of the methods were found to be suitable for the determinations. The average results of within-day and between-day RSDs were 5.64% and 7.85% respectively, the mean recovery was 97.66% for the concentration ranges studied. The pharmacokinetic parameters Tmax, Cmax, AUC and CLs were S-(-)-nimodipine (2.1 +/- 0.3) h, (197 +/- 5) microgram.L-1, (656 +/- 18) mL.min-1, (0.30 +/- 0.03) microgram.h.L-1, and R-(+)-nimodipine (1.7 +/- 0.5) h, (128 +/- 4) microgram.L-1, (381 +/- 4) mL.min-1, (0.53 +/- 0.03) microgram.h.L-1, respectively. The S-(-)-nimodipine concentration was 2.23 and 1.97 times as high as that of R-(+)-nimodipine in heart and in cerebrum respectively and there was almost only S-(-)-nimodipine in cerebellum. But R-(+)-nimodipine concentration was 1.57, 3.69 and 4.20 times as high as that of S-(-)-nimodipine in major excretion organs such as kidney, spleen and liver respectively.</p><p><b>CONCLUSION</b>The experimental results obtained by using the achiral and chiral liquid chromatography showed that the differences between enantiomers were apparent for the pharmacokinetics in rat plasma, and very significant for the distributions in major target tissues heart, cerebrum and cerebellum, and main elimination tissues kidney, spleen and liver.</p>
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Estereoisomerismo
/
Sangue
/
Farmacocinética
/
Bloqueadores dos Canais de Cálcio
/
Distribuição Tecidual
/
Nimodipina
/
Química
/
Cromatografia Líquida de Alta Pressão
/
Área Sob a Curva
/
Métodos
Tipo de estudo:
Estudo prognóstico
Limite:
Animais
Idioma:
Inglês
Revista:
Acta Pharmaceutica Sinica
Ano de publicação:
2003
Tipo de documento:
Artigo
Similares
MEDLINE
...
LILACS
LIS