The quassinoid-rich standardized extract of Eurycoma longifoia extract (TAF2) was found to possess various biological activities. However, the poor oral bioavailability of the bioactive quassinoids, 13α(21)-epoxyeurycomanone (EP) and eurycomanone (EN) in TAF2 necessitated a new formulation design to be developed. A lipid-based solid dispersion was formulated and the bioavailabilities of EP and EN were significant improved compared with the conventional powder-filled capsules. A double peak phenomenon was identified in the plasma concentration-time curve. The gastric emptying and variability of GIT absorption, the probable causes of the double peak phenomenon, were studied by administering TAF2 solid dispersion to Sprague Dawley rats. As marker compounds, theophylline and sulfasalazine were used to determine the gastric emptying and variability of GIT absorption. The percentage absorbed of the markers was calculated using Wagner-Nelson method. The results showed that 50 % of theophylline was absorbed at 3 h, indicating the transit time of TAF2 solid dispersion from the stomach to the small intestine. Whereas, the 50 % of sulfapyridine, the metabolite of sulfasalazine, was absorbed at 8 h, reflected time of TAF2 solid dispersion to reach the colon. The concentration of TAF2 in colon was 74.36 % for EP and 80.27 % for EN, respectively. The results indicated that the delayed gastric emptying and colon absorption were the causes of double peak phenomenon. Thus, the delayed onset of in vivo activity of the quassinoids in E. longifolia was probably due to the delay of gastric emptying and colon absorption.
Background:
TJAB1099 is a novel, highly active inhibitor of human enterovirus 71
(HEV71), which is a most commonly found virus leading to Hand-Foot-Mouth Disease (HFMD). However,
the TJAB1099 could not be detected in the plasma using a regular HPLC-UV detection during the
pharmacokinetic study due to the poor solubility, which in turn limited the release prior to be absorbed
by the gastrointestinal tract.
Objective:
The objectives of the present study were to improve the solubility of TJAB1099 by preparing
formulation and develop an Ultra Performance Liquid Chromatography Tandem Mass Spectrometry
(UPLC-MS/MS) method applied to the pharmacokinetic study.
Methods:
The TJAB1099 was prepared as a phospholipid complex that intends to increase the watersolubility
and subsequently improving TJAB1099 exposed in the circulation system. A highly sensitive
UPLC-MS/MS method was developed for the pharmacokinetic study, in which the pharmacokinetic
parameters were determined following oral and intravenous administration of 5 mg/kg and 1 mg/kg of
TJAB1099 in rats, respectively.
Results:
The precisions for the method were less than 12.8%, while the accuracies were in the range of
90.8 - 98.0% and 96.1 - 99.6% for within-day and between-day, respectively. The mean recoveries for
TJAB1099 and terfenadine (internal-standard, IS) were 85.0 ± 5.4% and 92.4 ± 4.1%, respectively. The
pharmacokinetic study revealed that the Cmax of TJAB1099 after oral administration can reach 6.84 ±
2.43 ng/mL, while the Tmax is 0.70 ± 0.11 h. The AUC0-12 is 19.81 ± 11.07 µg/mL/h. However, the absorption
was poor with an absolute oral bioavailability of 0.62.
Conclusion:
The UPLC-MS/MS method was successfully applied in the pharmacokinetic study of
TJAB1099 in rats.
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