• Journal of Pharmaceutical Investigation
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• 제36권3호
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• pp.157-160
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• 2006

This study investigated the effect of clarithromycin on the pharmacokinetics of ambroxol in rats. The pharmacokinetic parameters of ambroxol in rats were determined after the oral administration of ambroxol (12 mg/kg) in the presence or absence of clarithromycin (5 or 10 mg/kg). Compared with the control (given ambroxol alone), coadministration of clarithromycin significantly (p<0.05 at 5 mg/kg; p<0.01 at 10 mg/kg) increased the area under the plasma concentration-time curve (AUC), peak plasma concentrations $(C_{max})$ and absorption rate constant $(K_a)$ of ambroxol. Clarithromycin increased the AUC of ambroxol in a dose dependent manner within the dose range of 5 to 10 mg/kg. The absolute bioavailability (AB%) of ambroxol in the presence of clarithromycin was significantly higher than that of the control (p<0.05 at 5 mg/kg; p<0.01 at 10 mg/kg), and the relative bioavailability (RB%) of ambroxol with clarithromycin was increased by 1.32-to 1.71-fold. However, there were no significant changes in time to reach peak concentration $(T_{max})$ and terminal half-life $(T_{1/2})$ of ambroxol in the presence of clarithromycin. Coadministration of clarithromycin enhanced the bioavailability of ambroxol, which may be due to the inhibition of intestinal and hepatic metabolism of ambroxol by CYP 3A4. Further studies for the potential drug interaction are necessary since ambroxol is often administrated concomitantly with clarithromycin in humans.

• 한국임상약학회지
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• 제20권3호
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• pp.200-204
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• 2010

The purpose of this study was to investigate the effect of ticlopidine on the pharmacokinetics of nimodipine in rats. Pharmacokinetic parameters of nimodipine were determined in rats after oral administration of nimodipine (16 mg/kg) with or without ticlopidine (3 or 10 mg/kg). Ticlopidine inhibited cytochrome P450 (CYP)3A4 activity. Ticlopidine significantly (p<0.05, 10 mg/kg) increased the area under the plasma concentration-time curve (AUC) of nimodipine and ticlopidine significantly (p<0.05, 10 mg/kg) prolonged the terminal half-life ($t_{1/2}$) of nimodipine. Ticlopidine significantly (p<0.05, 10 mg/kg) decreased the total body clearance ($CL_t$). The absolute bioavailability (AB%) and relative bioavailability (RB%) of nimodipine by presence of ticlopidine were increased by 14% and by 42%, respectively, compared to the control. Based on these results, the increased bioavailability of nimodipine might be due to inhibition of the metabolizing enzyme cytochrome P450 (CYP)3A4 in the liver or intestinal mucosa and/or reducing total body clearance by ticlopidine.

• 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.

• Archives of Pharmacal Research
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• 제17권2호
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• pp.80-86
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• 1994

The bioavailability of digoxin generic tablets manufactures in Korea (formulations A & B) wwere compared to a standard (formulation C; Lanoxin brand digoxin, Burroughs Wellcome, USA) in 12 healthy Korean male volunteers (mean age 31.4 years) in a single dose, randomized, complete block crossover study. Using a latin square design, each of the subjects was randomized to the order number and allocated to each of the three treatments of 0.5mg oral digoxin. Digoxin conc4ntrations in serum and urine samples collected for 48 hours after dosing were measured by fluoprescence polarization immunoassy and radioimmunoassy, respectively. Treatments were compared by using nonlinear least squares regession analysis to evaluate the following pharmacokinetic parameters : maximum serum concentation $(C_{max})$; time of maximum serum concentation $(T_{max})$; area under the serum concentration-time curve $AUC_{0-12}$, $C_{max}$\;and\;(AUC_{0-12})$; and cummulative urinary excretion for 0-48 hours $(CLE_{0-48}.\;Mean\;AUC_{0-12},\;C_{max},\;and\;CUE_{0-48}$ values for formulations B and C were significantly different from formulation A (P<0.001), but not significantly diffeerent form each other. Basede on $AUL_{0-12}\;and\;CUE_{0-48}$ respectively, the relative availability of formulation B was 87.5% and 89.6% and the relative availability of formultation A was 43% and 35% when compared to formulation C(the standard).

• 약학회지
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• 제39권5호
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• pp.487-494
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• 1995

Solid lipid microspheres (SLMs) were prepared using various lipids and solidifying agents, in order to enhance the gastrointestinal absorption of Cyclosporine A (Cs A) which is a practically water-insoluble drug with low systemic bioavailability. Egg lecithin and HCO-60 (polyoxyethylated 60 mol, hydrogenated castor oil) were used as lipids. Stearic acid and stearyl alcohol were used as solidifying agents. Emulsion concentrates containing Cs A were prepared by mixing the melted lipid and solidifying agent with water, employing bile salts as a cosurfactant. SLMs were obtained by dispersing the warm emulsion concentrate in cold distilled water under mechanical stirring, followed by freeze drying. Physical characteristics of each SLM were investigated by particle size analysis, optical microscopy and scanning electron microscopy. Mean particle size of SLMs was in the range of 30 to 40.mu.m. The SLMs were in good appearance with spherical shape before freeze drying, but were deformed partially after freeze drying. Drug loading efficiencies of SLMs were observed as high as 80 to 90% in average. The systemic bioavailability of Cs A from different SLM formula was investigated in rats following oral administration. Cs A in whole blood was extracted and assayed by HPLC. SLMs revealed the higher bioavailabilities than the standard formula based on the marketed product. SLMs might have several advantages over standard formula for enhanced gastrointestinal absorption, controlled release properties, high loading capacity of the water-insoluble drug, and feasibility of solid dosage forms with better stability in storage.

• Archives of Pharmacal Research
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• 제25권5호
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• pp.572-584
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• 2002

Rapid development in molecular biology and recent advancement in recombinant technology increase identification and commercialization of potential protein drugs. Traditional forms of administrations for the peptide and protein drugs often rely on their parenteral injection, since the bioavailability of these therapeutic agents is poor when administered nonparenterally. Tremendous efforts by numerous investigators in the world have been put to improve protein formulations and as a result, a few successful formulations have been developed including sustained-release human growth hormone. For a promising protein delivery technology, efficacy and safety are the first requirement to meet. However, these systems still require periodic injection and increase the incidence of patient compliance. The development of an oral dosage form that improves the absorption of peptide and especially protein drugs is the most desirable formulation but one of the greatest challenges in the pharmaceutical field. The major barriers to developing oral formulations for peptides and proteins are metabolic enzymes and impermeable mucosal tissues in the intestine. Furthermore, chemical and conformational instability of protein drugs is not a small issue in protein pharmaceuticals. Conventional pharmaceutical approaches to address these barriers, which have been successful with traditional organic drug molecules, have not been effective for peptide and protein formulations. It is likely that effective oral formulations for peptides and proteins will remain highly compound specific. A number of innovative oral drug delivery approaches have been recently developed, including the drug entrapment within small vesicles or their passage through the intestinal paracellular pathway. This review provides a summary of the novel approaches currently in progress in the protein oral delivery followed by factors affecting protein oral absorption.

• 생명과학회지
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• 제27권7호
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• pp.812-816
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• 2017

적색 아조류 타르색소인 아마란스는 인공식용색소로 식품, 화장품, 의약품에 광범위하게 사용되고 있음에도 불구하고, 경구로 복용하였을 때 위장관 흡수율이나 흡수특성에 대해 연구된 바가 없다. 본 연구의 목적은 아마란스의 정맥투여 또는 경구 투여 후 약동학 특성을 평가하고 diffusion chamber system을 이용하여 위장관 흡수율 및 투과도를 평가하고자 하였다. 정맥투여된 아마란스는 38.8분의 소실반감기로 빠르게 혈중에서 소실된다. 그러나 경구투여된 아마란스는 생체이용률도 55.6%로 높은 위장관 흡수율을 나타내며 408분까지 혈중농도가 증가하고 24시간까지 혈중에 남아있는 특성을 나타내었다. 이는 아마란스의 위장관 흡수가 오랫동안 지속적으로 일어나는 것을 의미한다. 이를 확인하기 위하여 소장의 흡수부위를 공장, 회장사부, 회장하부로 나누어 위장관 투과도를 평가하고 투과성이 잘 알려진 지표물질과 비교하였다. 연구결과 아마란스의 위장관투과성은 투과도가 매우 높은 caffeine의 1/3정도의 투과도를 보이고, 중등도의 투과도를 보이는 atenolol과 유사한 투과도를 나타내었으며 회장상부에서의 투과도가 가장 높았다. 결과를 종합하면, 아마란스는 경구투여된 뒤 지속적으로 흡수되며 흡수율도 50% 이상을 보이므로, 식품, 립케어 화장용품, 경구용 의약품에 아마란스 등의 색소가 포함될 경우에는 첨가량 등을 고려하여 신중하게 사용해야 할 것이다.

• 대한수의학회지
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• 제46권1호
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• pp.7-12
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• 2006

We have studied pharmacokinetics of a new anti-human immunodeficiency virus (HIV) agent VP-0501 and its amino acid prodrug VP-0501AL which is designed to improve oral bioavailability. After oral administration at 100 mg/kg dose in rats (n = 4), VP-0501 was not detectable in plasma (<50 ng/ml), while after the administration of VP-0501AL, VP-0501 was quantitatively detected, at least for 8 hrs, with Cmax of ca. $2.5{\mu}g/ml$ and AUC of $8hr^{\ast}{\mu}g/ml$. When VP-0501 was intravenously administered at 50mg/kg, this compound appeared at a marginal level in plasma with AUC of $2hr^{\ast}{\mu}g/ml$, $t_{1/2}$ of 2 hr, $C_0$ of $0.7{\mu}g/ml$, and MRT of 3 hr. On the other hand, with intravenous VP-0501AL at the same dose, both the prodrug VP-0501AL and its metabolite VP-0501 appeared comparatively at higher level in the plasma: pharmacokinetic parameters of VP-0501AL including $Vd_{\beta}$, AUC, $t_{1/2,{\beta}}$, $C_0$, $CL_{tot}$, and MRT were ca. 2 L/kg, $70hr^{\ast}{\mu}g/ml$, 2 hr, $180{\mu}g/ml$, 0.7 L/hr/kg, and 1 hr, respectively. These results demonstrate that attachment of amino acid alanine to VP-0501 is an effective approach for improvement of its oral bioavailability. Therefore, VP-0501AL is expected to become a new highly bioavailable and potent anti-AIDS drug candidate/lead compound.

• Journal of Pharmaceutical Investigation
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• 제24권1호
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• pp.11-16
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• 1994

In order to reduce the systemic side effects and gastrointestinal irritation of ketoprofen after its oral administration, it was formulated as a 3% ketoprofen gel (ID-GEL) with Pluronic F-127. The pharmacokinetic characteristics of ID-GEL was evaluated following its transdermal application on the dorsal skin of rats at the dose of 9 mg/kg in reference to those of existing 3% ketoprofen gels. Even though the maximum concentration of 810 ng/ml was reached at 6 hrs postdose, the plasma concentration was kept almost constant until 24 hrs postdose, which suggested that ketoprofen was released continuously from the gel during this period. The bioavailability of ID-GEL was two times higher than those of existing 3% ketoprofen gels, based on the calculated area under the plasma concentration-time curves after the percutaneous administration.

• Journal of Pharmaceutical Investigation
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• 제18권4호
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• pp.187-195
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• 1988

Poorly permeable $Eudragit^{\circledR}$ RS 100 polymer was used as a wall material for the microencapsulation of zipeprol dihydrochloride by a phase separation method from chloroform-cyclohexane system with 5% polyisobutylene in cyclohexane, and microcapsules obtained were evaluated in vitro by particle size analysis, scanning electron microscopy, drug release test and in vivo bioavailability test in rats. The mechanism of drug release from microcapsules appeared to fit Higuchi matrix model kinetics. The area under the first moment of plasma concentration-time curve of the microcapsules obtained was considerably increased (p<0.05) as compared with that from zipeprol dihydrochloride oral solution. Therefore, it may be suggested that $Eudragit^{\cirledR}$ RS 100 coated zipeprol dihydrochloride microcapsules can be used as a sustained release medication.