• Archives of Pharmacal Research
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• v.19 no.5
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• pp.348-352
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• 1996

The antioxidant efficacy of aspalatone, a new antithrombotic agent, has been recognized in the neurotoxic model and in the cardiotoxic model in proliminary studies. We examined the specific activity of antiosidnat enzyme in the rat blood following administrations of aspirin, maltol, aspirin together with maltol, salicylmaltol (major metabolite of aspalatone) and aspalatone, respectively. Our assessment showed that salicylmaltol, maltol, aspalatone enhanced antiperoxidative activity. In addition, neither aspirin nor combination of aspirin and maltol, showed any significant effect on the activity of antioxidant enzyme. Because $H_{2}$$O_{2}$ accumulation may stimulate the thrombogenesis in blood, the result suggests that the induction of blood antiperoxidative activity produced by aspalatone may have beneficial effects on the thrombogenesis.

• Biomolecules & Therapeutics
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• v.6 no.2
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• pp.151-158
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• 1998

Aspalatone, a new antithrombotic agent, was administered orally to pregnant Sprague-Dawley rats during the organogenetic period at dose levels of 0, 20, 100 and 500 mg/kg/day. All dams were subjected to caesarean section on day 20 of pregnancy. Effects of test substance on dams and embryonic development of F1 fetuses were examined There were treatment-related decreases in body weight and food consumption in the 500 mg/kg group. There was a increase in the spleen weight in the 100 and 500 mg/kg groups. Develo-pmental toxicity was evident as decreased fetal body weights and increased fetal malformations in the 500 mg/ kg group. External and skeletal malformations of fetuses occurred at an incidence of 1 and 8.2%, respectively. In addition, there was a delay in ossification of sternebrae and sacrocaudal vertebrae in the 500 mg/kg group. The results show that the no observed adverse effect dose level (NOAEL) for maternal toxicity was 20 mg/kg/ day and for developmental toxicity was 100 mg/kg/day.

• Biomolecules & Therapeutics
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• v.8 no.4
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• pp.332-337
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• 2000

Physicochemical properties of aspalatone (acetylsalicylic acid maltol ester, AM), which has been recently found to have an antithrombotic effect, were studied in terms of solubility, dissolution, partition coefficient (Pc) and stability. The solubility of AM at 37$^{\circ}C$ was about 1.2 mg/ml and the P$_{c}$ value for n-octanol/water and chloroform/water was 11.4 and 382.6, respectively. Dissolution rates of AM at pH 1.2 and 6.8 were more than 80% within 30 min. The degradation of AM followed apparent first-order kinetics, and was dependent on temperature, pH and ionic strength. From the pH-rate profile, the optimal pH was found to be at around 4.0. Half-lives at pH 1.2 and 6.8 were 33.5 and 44.4 hr, respectively. The degradation rate of AM at pH 1.2 was somewhat faster than that of aspirin, but at pH 7.0, the degradation rate of AM was slower than that of aspirin.n.

• Journal of Pharmaceutical Investigation
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• v.29 no.4
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• pp.355-360
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• 1999

Triflusal is a new antithrombotic agent which inhibits both platelet cyclooxygenase and c-AMP phosphodiesterase activity. The purpose of the present study was to evaluate the bioequivalence of two triflusal capsules, $Disgren^{TM}$ (Myung-In Pharmaceutical Co., Ltd.) and $Tigriri^{TM}$ (Hana Pharmaceutical Co., Ltd.) according to the guidelines of Korea Food and Drug Administration (KFDA). Eighteen normal male volunteers, $22.94{\pm}1.83$ in age and $63.7l{\pm}10.43$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one capsule containing 300 mg of triflusal was orally administered, blood was taken at predetermined time intervals and the concentrations of triflusal in serum were determined using HPLC method with UV detector. Pharmacokinetic parameters such as $AUC_t$ $C_{max}$ and $T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters. The results showed that the differences in $AUC_t$ $C_{max}$ and $T_{max}$ between two capsules were -0.30%, 0.81 % and -3.03%, respectively when calculated against the $Disgren_{TM}$ capsule. The powers $(1-{\beta})$ for $AUC_t$ $C_{max}$ and $T_{max}$ were 98.29%,84.73% and 81.02%, respectively. Minimum detectable differences $({\Delta})$ at ${\alpha}=0.1$ and $1-{\beta}=0.8$ were all less than 20% (e.g., 12.91%, 18.46% and 19.65% for $AUC_t$ $C_{max}$ and $T_{max}$ respectively). The 90% confid,ence intervals were all within ${\pm}20%$(e.g., $-8.97{\sim}8.37$, $-11.58{\sim}13.22$ and $-16.23{\sim}10.17$ for $AUC_t$ $C_{max}$ and $T_{max}$, respectively). All of the above parameters ($1-{\beta}, {\Delta}$ and 90% confidence intervals) met the criteria of KFDA for bioequivalence, indicating that $Tigriri^{TM}$ capsule is bioequivalent to $Disgren^{TM}$ capsule.