AIMTo investigate the differences of pharmacokinetic behavior and tissue distribution of nimodipine and its two enantiomers in rats.

METHODSA high-performance liquid chromatographic method with an ODS column (150 mm x 4.6 mm ID) and a mobile phase of methanol-water (70:30) 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 (85:15) as mobile phase was used to determine its two enantiomers. Nimodipine was monitored at 236 nm wavelength.

RESULTSThe 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.

CONCLUSIONThe 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.