• Biomolecules & Therapeutics
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• 제19권2호
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• pp.237-242
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• 2011

This study was designed to investigate the effects of glipizide on the pharmacokinetics of carvedilol after oral or intravenous administration of carvedilol in rats. Clinically carvedilol and glipizide can be prescribed for treatment of cardiovascular diseases as the complications of diabetes, and then, Carvedilol and glipizide are all substrates of CYP2C9 enzymes. Carvedilol was administered orally or intravenously without or with oral administration of glipizide to rats. The effects of glipizide on cytochrome P450(CYP) 2C9 activity and P-gp activity were also evaluated. Glipizide inhibited CYP2C9 activity in a concentration-dependent manner with 50% inhibition concentration ($IC_{50}$) of 18 ${\mu}M$. Compared with the control group, the area under the plasma concentration-time curve (AUC) was significantly increased by 33.0%, and the peak concentration ($C_{max}$) was significantly increased by 50.0% in the presence of glipizide after oral administration of carvedilol. Consequently, the relative bioavailability (R.B.) of carvedilol was increased by 1.13- to 1.33-fold and the absolute bioavailability (A.B.) of carvedilol in the presence of glipizide was increased by 36.8%. After intravenous administration, compared to the control, glipizide could not significantly change the pharmacokinetic parameters of carvedilol. Therefore, the enhanced oral bioavailability of carvedilol may mainly result from inhibition of CYP2C9-mediated metabolism rather than both P-gp-mediated effl ux in the intestinal or in the liver and renal elimination of carvedilol by glipizide.

• Journal of Pharmaceutical Investigation
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• 제28권2호
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• pp.109-113
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• 1998

This study is purposed to develop the sustained release and bioavailability of piracetam (PA). The use of alginate beads as a means to achieve sustained release of piracetam was evaluated in comparison with that of piracetam alone. In the PA-sodium alginate(SA) beads was confirmed by differential scanning calorimetry thermogram(DSC), indicating a relative shift of an endometric peak of PA to higher temperature. The changes in dissolution rates from PA-SA beads and PASA beads coated by chitosan(CHO) were significantly slower than that of intact PA. The release rate of PA-SA in the gastric fluid was markedly decreased compared with that in the intestinal fluid, suggesting that PA is mostly released in the intestinal fluid. However, the PA/SA ratio scarcely affected the release profile. The blood concentration- time curves of PA, PA-SA and PA-SA-CHO were obtained by oral administration to rats. $T_{max}$ of PA, PA-SA and PA-SA-CHO were 1, 10 and 6 hours, respectively. It was confirmed that the release of PA was prolonged by the formulation of PA-SA beads and PA-SA-CHO beads.

• Journal of Pharmaceutical Investigation
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• 제27권3호
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• pp.225-231
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• 1997

For the effective administration of naloxone, we attempted to investigate the naloxone sustained-release implants. Using the biodegradable polymer, poly[(diethyl glutamate)-co-(ethyl glycinate)phosphazenes](PGGP), the implantable devices containing naloxone hydrochloride(NLX HCl) and naloxone base(NLX) were prepared. The release rates of NLX and NLX HCl were compared. Influences of NLX contents on release rates were examined. For pharmacokinetic studies, NLX and NLX HCl loaded devices were implanted subcutaneously in rabbits and then the plasma concentrations of NLX were determined by HPLC(ECD). NLX-containing devices were implanted with various doses and pharmacokinetic parameters according to dose were calculated. The relative bioavailabilities were evaluated and compared. Incorporation of NLX in the polymer leaded to a slow release. There were no differences of release rates based on drug contents. In pharmacokinetic parameters determined in 216 hours, NLX loaded devices resulted in enhanced bioavailability with the higher AUC (p<0.01) than NLX HCl loaded devices and MRT was significantly (p<0.05) increased. This result demonstrates that NLX is more suitable for sustained release devices than NLX HCl. Therefore it is anticipated that the effective concentrations of naloxone could be maintained for longer periods and bioavailabilities could be improved by naloxone sustained-release implants, with varying drug base/hydrochloride.

• Biomolecules & Therapeutics
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• 제18권4호
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• pp.469-476
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• 2010

This study was to investigate the effect of apigenin on the bioavailability of paclitaxel after oral and intravenous administration in rats. The effect of apigenin on P-glycoprotein (P-gp), cytochrome P450 (CYP)3A4 activity was evaluated. The pharmacokinetic parameters of paclitaxel were determined in rats after oral (40 mg/kg) or intravenous (5 mg/kg) administration of paclitaxel with apigenin (0.4, 2 and 8 mg/kg) to rats. Apigenin inhibited CYP3A4 activity with 50% inhibition concentration ($IC_{50}$) of 1.8 ${\mu}M$. In addition, apigenin significantly inhibited P-gp activity. Compared to the control group, apigenin significantly increased the area under the plasma concentration-time curve (AUC, p<0.05 by 2 mg/kg, 59.0% higher; p<0.01 by 8 mg/kg, 87% higher) of oral paclitaxel. Apigenin also significantly (p<0.05 by 2 mg/kg, 37.2% higher; p<0.01 by 8 mg/kg, 59.3% higher) increased the peak plasma concentration ($C_{max}$) of oral paclitaxel. Apigenin significantly increased the terminal half-life ($t_{1/2}$, p<0.05 by 8 mg/kg, 34.5%) of oral paclitaxel. Consequently, the absolute bioavailability (A.B.) of paclitaxel was significantly (p<0.05 by 2 mg/kg, p<0.01 by 8 mg/kg) increased by apigenin compared to that in the control group, and the relative bioavailability (R.B.) of oral paclitaxel was increased by 1.14- to 1.87-fold. The pharmacokinetics of intravenous paclitaxel were not affected by the concurrent use of apigenin in contrast to the oral administration of paclitaxel. Accordingly, the enhanced oral bioavailability by apigenin may be mainly due to increased intestinal absorption caused via P-gp inhibition by apigenin rather than to reduced renal and hepatic elimination of paclitaxel. The increase in the oral bioavailability might be mainly attributed to enhanced absorption in the gastrointestinal tract via the inhibition of P-gp and reduced first-pass metabolism of paclitaxel via the inhibition of the CYP3A subfamily in the small intestine and/or in the liver by apigenin. It appears that the development of oral paclitaxel preparations as a combination therapy is possible, which will be more convenient than the i.v. dosage form.

• 약학회지
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• 제39권4호
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• pp.438-443
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• 1995

Four different pseudopolymorphs of amoxicillin-trihydrate, dehydrate, monohydrate and anhydratewere prepared and characterized by UV spectrophotometry, DSC, and TGA. In vitro dissolution studies of four pseudopolymorphs were carried out in pH 6.8 phosphate buffer at $37^{\circ}C$ by means of a rotating disk method. The effect of four pseudopolymorphs on bioavauability of amoxicillin was studied in healthy 6 subjects using urinary excretion method. The dissolution result was shown in the sequence, trihydrate(95.5%)>monohydrate(83.5%)>anhydrate(67.6%)>dihydrate(15.8%). The urinary excretion rate of anhydrate could not be detected and the dissolution results agreed well with in vivo phannacoldnetic study results. The effects of storage conditions, milling and compression on the pseudopolymorpnc transformation were investigated by thermal methods. The results showed that four pseudopolymorphs were not transformed and they were very stable.

• Journal of Pharmaceutical Investigation
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• 제10권3호
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• pp.27-32
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• 1980

This paper was to investigate the biovailability of antipyrine, ampicillin and protein binding in pathological rats and rabbits pretreated with typhoid vaccine. The results are as follows: The absorption of antipyrine and ampicillin respectively were reduced in rats pretreated with typhoid vaccine as compared with those of normal rats. Especially absorption of ampicillin was more decreased than those of antipyrine. The blood level of antipyrine in severe state was decreased but in mild state. Blood level of ampicillin was decreased in mild state as well as in severe state. Relative bioavailability of antipyrine and ampicillin were mostly decreased in rabbits pretreated with typhoid vaccine except that of antipyrine in mild state. Renal clearance of antipyrine was not affected, but that of ampicillin was apt to increase. Protein binding of antipyrine and ampicillin were decreased by high concentration of typhoid vaccine.

• Journal of Pharmaceutical Investigation
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• 제20권1호
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• pp.1-5
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• 1990

Effect of an angiotensin inhibitor (AAS; loading dose of 25, 50, $100{\mu}g/kg$ and maintenance dose of 12.5, 25,$50{\mu}g/ka/hr$) on the pharmacokinetics of propranolol (4 mg/kg i.v.) was studied in rabbits. Plasma concentrations and relative bioavailability of propranolal increased upto 127-175% by AAS coinjection. The urinary excretion of propranolol decreased by AAS. Dosage regimen of propranolol should be adjusted when it is administered with AAS.

• 한국지하수토양환경학회:학술대회논문집
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• 한국지하수토양환경학회 2000년도 추계학술대회
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• pp.196-201
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• 2000

The influence of adsorption on cadmium toxicity to soil microorganisms in smectite-rich soils and sediments was quantified as a function of solution and sorbent characteristics. Adsorption and surface complexation experiments were conducted to infer Cd sorption mechanisms to a reference smectite and three fractions of a Veritsol soil, and to elucidate the effects of the surface complexation on Cd bioavailability and toxicity in soils and sediments. Cadmium adsorption isotherms conformed to the Langmuir adsorption model, with adsorptive capacities of the different samples dependent on their characteristics. Equilibrium geochemical modeling (MINTEQA2) was used to predict the speciation of Cd in the soil suspensions using Langmuir and Triple Layer surface complexation models. The influence of adsorption and surface complexation on cadmium toxicity to soil microorganisms was assessed indirectly through the relative change in microbial hydrolysis of fluorescein diacetate (FDA) as a function of total Cd concentration and sorbent characteristics. Adsorption decreased the toxicity of Cd to soil microorganisms. Inner-sphere complexation is more effective than outer-sphere complexation in reducing the bioavailability and toxicity of heavy metals in soils and sediments.

• 약학회지
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• 제33권6호
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• pp.345-349
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• 1989

This paper was attempted to investigate effect of angiotensin inhibitor (loading dose 25, 50, $100{\mu}g/kg$ and maintenance dose 12.5, 25, $50{\mu}g/kg/hr$) on the pharmacokinetics of furosemide (5 mg/kg i.v) in rabbit. The plasma concentrations of furosemide increased by angiotensin inhibitor and the relative bioavailability of furosemide increased from 118.1% to 193.2% by the inhibitor. The protein binding of furosemide decreased by angiotensin inhibitor in bovine serum albumin ($2.17\;{\times}\;10^{-4}M$) by equilibrium dialysis method. Consequently, dosage regimen of furosemide might be adjusted carefully when furosemide is administered with angiotensin inhibitor.

• Journal of Pharmaceutical Investigation
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• 제16권1호
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• pp.31-35
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• 1986

Effect of ethanol on the absorption rate, blood level and bioavailability of sulfamethazine (SM) in rats was determined. Absorption rate of SM was determined both by the in vitro and in situ experiment. In vitro, absorption rate of SM in rat small intestine was increased by 0.3, 1.0 and 3.0% ethanol. In situ, absorption rate of SM was increased by 0.3 and 1.0% ethanol but not by 3.0% ethanol. After oral administration, blood level of SM was elevated and relative bioavailability was significantly increased to 114.8% at the dose of 0.6g/kg ethanol but not significantly at the dose of 3.0g/kg ethanol. The time for attainment of peak blood level was changed from 2.5 to 1.5hr. Ethanol enhanced absorption rate constant of SM significantly and reduced elimination rate constant of SM administered orally at the dose of 0.6g/kg ethanol.