[Stereoselective chronopharmacokinetics of hydratropic acid in rats]

The circadian rhythms of hydratropic acid (HTA) pharmacokinetic parameters were studied by using consinor method. Under standard light-dark cycle, the T1/2 beta and CL of S(+)-HTA, T1/2 beta of R(-)-HTA and CL, MRT of RS (+/-)-HTA were found to have circadian rhythm. Circadian rhythms were also found in the T1/2 beta and AUC of S (+)-HTA, CLS of R(-)-HTA and RS(+/-)-HTA under reverse light--dark cycle. Stereoselective circadian rhythms were found in CL of S(+)-HTA under standard light-dark cycle and in T1/2 beta and AUC of S(+)-HTA and CL of R(-)-HTA under reverse light-dark cycle. After ip administration of RS(+/-)-HTA to rat under two different light-dark cycles, the peak phases of circadian rhythms in the biotransformation of R(-)-HTA to S(+)-HTA in rat were both at the end of the dark phase. This suggests that administration of the drug at early morning is a recommendable scheme for chronotherapy with HTA.