Abstract:
The circadian rhythms of hydratropic acid (HTA) pharmacokinetic parameters were studied by using consinor method. Under standard light—dark cycle, the
T1/2β and CL of
S(+)-HTA,
T1/2βof
R(—)-HTA and CL, MRT of
RS (±)-HTA were found to have circadian rhythm. Circadian rhythms were also found in the
T1/2 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
T1/2β 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.