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 T_1/2β and CL of S(+)-HTA, T_1/2βof R(—)-HTA and CL, MRT of RS (±)-HTA were found to have circadian rhythm. Circadian rhythms were also found in the T_1/2 β 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 T_1/2β 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.