• Proceedings of the PSK Conference
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• 2001.10a
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• pp.311.2-312
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• 2001

• Mass Spectrometry Letters
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• v.14 no.4
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• pp.141-146
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• 2023

Liraglutide is a medication prescribed for the management of type 2 diabetes and chronic obesity. A simple, sensitive, and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantitative analysis of liraglutide in rat plasma. After a simple protein precipitation step, liraglutide was chromatographically separated using the ACQUITY Premier Peptide BEH C18 Column with mobile phases comprising 50% acetonitrile and 50% methanol, and water with 0.3% FA. Positive ion electrospray ionization in multiple reaction monitoring mode was used to achieve detection. Good linearity was observed in the 5-600 ng/mL concentration range (R² > 0.99). Liraglutide had intra- and inter-day precision values of 2.13%-9.86% and 4.14%-8.36%, respectively. The accuracy ranged from -2.36% to 2.58%. The recovery and matrix effect were within acceptable limits. This selective LC-MS/MS method was used to study the pharmacokinetic properties of liraglutide after subcutaneous administration in rats.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.04a
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• pp.106-106
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• 1997

Cinmetacin, one of the candidate of NSAID of arylacetate group was developed into a prodrug SJ-151 with butendiol group to minimize its gastrointestinal side effects. We studied its excretion and distribution after single oral administration in rats. Male rats were orally administered with 30, 60, 80 or 120mg/kg of SJ-151 and their urine and stool were collected at 0, 6, 12, 24 and 48 hour after administration. To evaluate its tissue distribution, 120mg/kg of SJ-151 was orally given and samples of blood, liver, kidney and brain were taken at 0.5, 1, 2, 4, 8, 24, and 48 hour of administration. As results, less than 0.1% of administered SJ-151 was detected in 48 hour collected urine as its metabolite cinmetacin. 33-50% of administered SJ-151 was observed in 48 hour collected stool as SJ-151. 3-7% of excreted SJ-151 was observed in 48 hour collected stool as cinmetacin. SJ-151 and cinmetacin were not detected in the brain regardless of dosage. SJ-151 was detected neither in kidney nor in liver. Only cinmetacin was observed in both organs with kidney concentrations higher than liver throughout the observation period. On the whole, organ concentration of cinmetacin fluctuated through 0.1-1.5 times that of plasma. As no reports on the metabolism of SJ-151 or cinmetacin in specific organs has been published yet, any detailed explanation of these results needs further study and the plasma concentration profile of rats showed remarkable interspecies difference with dogs.

• Journal of Nutrition and Health
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• v.38 no.5
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• pp.335-343
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• 2005

Rodent models have been used to study the anticarcinogenic properties of the soy isoflavones, particularly genistein, but there is little information regarding the pharmacokinetics of the absorption and excretion of genistein. In this study, rats were given a single oral dose of genistein (20 mg/kg body wt) or an equivalent dose as Myougjoonamul-kong and Myoungjoonamul soy sprouts. Concentrations of genistein were measured in plasma, urine and feces at intervals up to 48hr after dosing. Maximum peak of plasma genistein concentration is 8 hr after dosing, and its concentration is 13.2, 7.4mol/L in soy and soy sprout-treated rats, respectively. In pure genistein treated rats, maximum peak of plasma genistein concentration is 2hr after dosing (5.7 mol/L). The percentage of dose recovered in urine over 48hr was not different between groups ($21.2\%$ soy treated; $18.2\%$ soy sprout treated; $16.1\%$ pure genistein treated). There were no significant differences between groups in the recovery of genistein in feces ($19.5\%,\;7.5\%\;and\;15.7\%$ of doses, respectively). $6.9\%\;and\;6.07\%$ of the daidzein from the soy and soy sprout treated was recovered in the feces.

• Archives of Pharmacal Research
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• v.17 no.2
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• pp.124-130
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• 1994

Plasma phamacokinetics and renal excretion of theophylline (TP) and its metabolities were ivnestigated in rats. Plasma concentrations of TP declined in a monoexponential manner, while those of 1-methyluric (MU) and 1,3-dimethyluric(DMU) declined in a biexponential manner upon respective iv bolus injection of each compound at 6mg/kg dose. The total body clearances $(CL_r)$ of the metabolites were 4-6 fold larger than that of TP, while the distribution volumes of them at steady-state $(Vd_{ss})$ were 40-50% smaller than that of TP. The metabolites showed their plasma peaks in 30 min after iv injection of TP indicating than that to MU. Renal excretion of TP and its metabolites was studied in urine flow rate (UFR)-controlled rats. The renal clearance $(CL_r)$ of TP was inversely related to pasma TP concentrations, and much smaller than the glomerular filtration rate (GFR) suggesting tubular secretion and profound reabsorption in the renal tubule. The $(CL_r)$ of each metabolite also showed that inverse relationship, but far exceeded GFR suggesting that tubular secretion than GFR by ip injection of probenecid (142.7 mg/kg). It supports that the metabolies are secreted in the renal tubule, and suggests that they share a common transport system in their sectrtion processes with probenecid. On the other hand, the $(CL_r)$ of TP was not affected significantly by the probenecid treatment. Considering the inverse relationship of TP between the $(CL_r)$ and its ploasma concentrations,no effect of probenecid on $(CL_r)$ of TP is most likely due to negligible contribution of the secretion to the overall $(CL_r)$ of TP.

• YAKHAK HOEJI
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• v.36 no.6
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• pp.591-597
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• 1992

The organ distribution of $[^3H]$-methotrexate-lactosaminated bovine serum albumin conjugates ($[^3H]$-MTX-LBSA) was investigated to examine their role as a liver-specific anticancer drug. Synthesis of lactosaminated bovine serum albumin(LBSA) with BSA, lactose and sodium cyanoborohydride through reductive amination was followed by its conjugation with methotrexate (MTX) and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC), thereby synthesizing [$[^3H]$-MTX-LBSA conjugates. Organ distribution and plasma elimination profiles were studied in male Wistar rats after intravenous injection of [$[^3H]$-MTX-LBSA conjugates. The fates of $[^3H]$-MTX and the $[^3H]$-MTX-BSA conjugates´fates were also investigated for comparison. The results showed that the plasma level of $[^3H]$-MTX-LBSA conjugates declined more rapidly than those of $[^3H]$-MTX-BSA and their liver concentration was significantly higher than those of other treatment (p<0.01). In addition, their uptake compared to the amount taken up by the liver (1 : 33.1 at 10 min, 1 : 24.1 at 120 min). All these suggested that MTX-LBSA conjugate is one of the drug delivery system (DDS) that is advanced in concentrating MTX in the liver and minimizing the renal toxicity of MTX.

• Korean Journal of Clinical Pharmacy
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• v.23 no.4
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• pp.322-326
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• 2013

Purpose: Telmisartan, an angiotensin receptor blocker has been known to be a potent blocker of both CYP2J2 and P-glycoprotein (P-gp) in vitro. This study aims to investigate the drug-drug interactions between telmisartan and ebastine, a CYP2J2 and P-gp substrate in rats. Method: Ebastine (10 mg/kg) was orally given in the presence and absence of telmisartan (4 mg/kg, p.o.). Heparinized blood was serially taken and the plasma concentrations of ebastine and its three metabolites (hydroxyebastine, carebastine and desalkylebastine) were determined using LC-MS/MS, and their pharmacokinetic parameters were compared. Results: Peak concentrations ($C_{max}$) and AUC of ebastine were significantly (p<0.05) increased in the presence of telmisartan by 2.1 and 1.9 times, respectively. While $C_{max}$ of hydroxyebastine was significantly increased by 1.9 times, the half-life of hydroxyebasteine was decreased significantly with telmisartan (p<0.05). There was no change in the pharmacokinetic parameters of carebastine, the active metabolite of ebastine, and desalkylebastine was not detected in plasma. The systemic exposure of ebastine was significantly augmented by telmisartan, indicating that telmisartan may enhance the absorption of ebastine by blocking P-gp. Conclusion: Although telmisartan may also partially contribute to inhibit the biotransformation to hydroxyebastine, the inhibitory action seemed to be overridden by the enhancement of absorption, because the generation of hydroxyebastine was not diminished. In spite of such interactions between telmisartan and ebastine, no clinical consequence could be expected due to no significant change of the active metabolite, carebastine.

• Korean Journal of Veterinary Research
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• v.35 no.4
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• pp.691-698
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• 1995

We used rats as the experimental animal for the elucidation of metabolic patterns and pharmacokinetic profiles of SMZ in the rat, by use of the urine and plasma from predetermined intervals, respectively. Information herefrom would give some insight into species differences and sex differences in the metabolism and pharamcokinetics of drugs, at least SMZ in particular. Results would be summarized as follows: 1. There were two hydorxy metabolites(5-hydroxysulfamethazine and 6-hydroxyethylsulfamethazine) and an acetyl derivative($N_4$-acetyl sulfamethazine) in the 24h-collected urine, on confirmation with each standard materials. There were also two unknown metabolites therein. 2. In the viewpoint of quantitative aspect, $N_4$-acetylsulfamethazine was the largest, hence it is assumed that the acetyl pathway is the major one in the metabolism of SMZ in the rat. 3. As regards sex difference in the rat, the male had more metabolic capacity than the female in metabolism of SMZ. 4. The concenteration-time curves of sulfamethazine(20mg/kg, po) in the plasma compartment were fitted to a one-compartment open model by use of a computer program(NONLIN). 5. There were significant differences(P<0.05) in the pharmacokinetics of sulfamethazine between two sexes in the rat, with higher disposition rate in the male. 6. The emergence of $N_4AcSMZ$ metabolized from SMZ was fast in the plasma of the rat. Half-life of $N_4AcSMZ$ was also. significantly different(P<0.05) between two sexes, suggesting differences in the eliminatory capacity of $N_4AcSMZ$.

• Journal of Pharmaceutical Investigation
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• v.30 no.1
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• pp.21-26
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• 2000

Bioavailability of ipriflavone (3-phenyl-7-isopropoxy-4H-I-benzopyran-4-one, IP), an antiosteoporotic drug with poor water-solubility, was studied for various types of pharmaceutical preparation in SD rats. The IP preparation types included (1) intact IP, (2) freezer milled IP (FIP), (3) freezer milled IP physically mixed with freezer milled poly-N-vinylpyrrolidone (PVP) (FIP+FPVP) and (4) spray-dried IP with PVP (SIP). Upon oral administration, SIP showed significantly higher absorption and elimination half-lives and the lag time $(t_{lag})$ than those of FIP+FPVP (approximately 2-fold). These results may be due to a sustained releasing effect of IP in the gastrointestinal tract by spray-drying with PVP. The $C_{max}$ of SIP was about 2 and 10 times higher than those of FIP+FPVP and FIP, respectively. The AUC of SIP was about 6 times higher than that of FIP+FPVP and 60 times that of FIP. Scanning electron microscopy (SEM) showed that SIP consisted of the finest particle size and minimal aggregation than other IP preparations. It is concluded that the IP formula prepared by the spray-drying method with PVP is the most effective approach to the improvement of bioavailability of IP.

• Korean Journal of Environmental Agriculture
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• v.30 no.2
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• pp.196-201
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• 2011

BACKGROUND: Bioavailability enhancement by solubilization of lipophilic drugs in nano-emulsion has been reported and it may be useful in pharmaceutical and nutraceutical products. This study was performed to compare in vivo bioavailability of nano-emulsion formulation with that of the general product as control. METHODS AND RESULTS: The pharmacokinetics assessment of Vitamin A, D and E complex of nanoemulsion formulation (LaVita), in comparison to the general product, was performed in the male rat plasma by a single oral dose at 20 mL/kg body weight (n=3/group). For nano-emulsion formulation (LaVita), $C_{max}$ of vitamin A and E in plasma were much higher and the area under the curve (AUC) of vitamin A, D and E were 14-63% higher, and the half-life of vitamin E was 2-fold longer than the general product. According to statistical analysis, each $C_{max}$ of vitamin A, D & E was significantly higher (p<0.01, 0.05 and 0.01, respectively) than that of general product. Half-life of vitamin A was significantly higher (p<0.01) and AUC of vitamin A and D were also significantly higher than the general product. CONCLUSION(s): Considering significant increment of $C_{max}$ and AUC, LaVita made of nano-emulsion could be more effective the absorption rate and extent for bioavailability of vitamin A, D & E than those of general product.