Asian Journal of Pharmacodynamics and Pharmacokinetics

Xu HY et al. Asian Journal of Pharmacodynamics and Pharmacokinetics 2009; 9(1):11-25
difference between the main pharmacokinetic
parameters of the two enantiomers. THP showed
significant stereoselective pharmaco- kinetics in rats
after an ig dose of the racemate. [50]
selective chiral HPLC method coupled with
achiral column was developed and validated to
separate and quantify THP enantiomers in dog
plasma. Chromatography was accomplished by two
steps: (1) racemic THP was separated from biological
matrix and collected on a Kromasil C18 column (150
mmx4.6 mm, 5µm) with the mobile phase
acetonitrile-0.1% phosphoric acid solution, adjusted
with triethylamine to pH 6.15 (47:53); (2)
enantiomeric separation was performed on a
Chiralcel OJ-H column (250 mmx4.6 mm, 5µm) with
the mobile phase anhydrous ethanol. The detection
wavelength was set at 230 nm. (+)-THP and (-)-THP
were separated with a resolution factor (Rs) of at
least 1.6 and a separation factor (alpha) greater than
1.29. Linear calibration curves were obtained over
the range of 0.025-4 µg·mL -1 in plasma for each of
(+)-THP and (-)-THP (R 2 >0.999) with a limit of
detection (LOD) of 0.005 µg·mL -1 and the recovery
was greater than 88% for each enantiomer. The
method was used to determine the pharmacokinetics
of THP enantiomers after oral administration of
racemic THP. The results presented herein showed
the stereoselective disposition kinetics of THP in
dogs and were a further contribution to the
understanding of the kinetic behavior of THP
analogues. [51]
The main objective of this study was to
determine the brain pharmacokinetics and tissue
distribution of THP enantiomers in rats after oral
administration of racemic THP (rac-THP). Rats (5
animals/group/per time) were given a single oral dose
of rac-THP and killed after different post-treatment
times. The concentrations of THP enantiomers in
plasma, cortex, cerebellum, diencephalon, brain stem,
striatum and hippocampus were measured using a
validated chiral HPLC method coupled with an
achiral column. The pharmacokinetic profiles of the
two enantiomers in six brain regions were
significantly different. The peak concentrations (C max )
and AUC 0-infinity values of the (-)-enantiomer were
significantly greater than the corresponding values
for the (+)-enantiomer while the striatum contained
the highest peak concentrations compared with the
plasma and other brain regions. The tissue
distribution studies also revealed significant
differences between the two enantiomers in all tissues
except the lung. The highest concentrations of both
enantiomers were found in the liver. The (-)/(+)-THP
ratios in six brain regions and other tissues were
consistent with that observed in plasma indicating
that the stereoselective disposition of THP in rat brain
and other tissues reflects the situation in plasma. [52]
THP is the active component in Rhizoma
corydalis and the medicine Yuanhu-Baizhi (YB),
which consists of Rhizoma corydalis and Radix
angelicae dahuricae. The aim of this work was to
compare pharmacokinetic features of THP
enantiomers in rats dosed with racemic THP
(rac-THP), Rhizoma corydalis, or YB extracts. A
single dose of rac-THP (5 mg·kg -1 ) or extracts of
Rhizoma corydalis and YB (both equivalent to 5
mg·kg -1 of rac-THP) was given orally to three groups
of Sprague-Dawley rats, respectively. Blood samples
were collected periodically and plasma
concentrations of THP enantiomers were determined
using an achiral-chiral HPLC method previously
reported, with some modifications. The C max ratio
(-/+) of THP was 2.91, 1.38, and 1.19, and the AUC 0
approximately infinity) ratio (-/+) of THP was 2.84, 1.50, and
1.35 in rats after dosed with rac-THP, extracts of
Rhizoma corydalis and YB, respectively. The mean
AUC 0 approximately infinity and C max of (+)-THP dosed with
YB extracts were 0.652 ± 0.30 µg·h·ml -1 and 0.148
±0.09 µg·ml -1 , significantly higher (P < 0.05) than
those dosed with rac-THP and Rhizoma corydalis
extracts. The mean AUC 0 approximately infinity and T max of
rac-THP dosed with YB extracts were 1.500 ± 0.56
µg·h·ml -1 and 2.12 ±1.1 h, significantly higher (P <
0.05) than those dosed with rac-THP or Rhizoma
corydalis extracts. These findings suggested the
stereoselectivity in pharmacokinetics of THP
enantiomers in rats was decreased when dosed in
plant form, while the AUC 0-approximately infinity of
rac-THP increased when YB extracts were dosed,
confirming the compatibility in drug combination of
Rhizoma corydalis and Radix angelicae dahuricae. [53]
The main objective of this study was to
determine the brain pharmacokinetics and tissue
distribution of THP enantiomers in rats after oral
administration of racemic THP (rac-THP). Rats (5
animals/group/per time) were given a single oral dose
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