• Mass Spectrometry Letters
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• v.9 no.2
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• pp.61-65
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• 2018

KPLA-012, a benzopyranyl 1,2,3-triazole compound, is considered a potent $HIF-1{\alpha}$ inhibitor based on the chemical library screening, and is known to exhibit anti-angiogenetic and anti-tumor progressive effects. The aim of this study was to investigate the pharmacokinetic properties of KPLA-012 in ICR mice and to investigate in vitro characteristics including the intestinal absorption, distribution, metabolism, and excretion of KPLA-012. The oral bioavailability of KPLA-012 was 33.3% in mice. The pharmacokinetics of KPLA-012 changed in a metabolism-dependent manner, which was evident by the low recovery of parent KPLA-012 from urine and feces and metabolic instability in the liver microsomes. However, KPLA-012 exhibited moderate permeability in Caco-2 cells ($3.1{\times}10^{-6}cm/s$) and the metabolic stability increased in humans compared to that in mice (% remaining after 1 h; 47.4% in humans vs 14.8% in mice). Overall, the results suggest that KPLA-012 might have more effective pharmacokinetic properties in humans than in mice although further studies on its metabolism are necessary.

• Korean Journal of Clinical Pharmacy
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• v.10 no.3
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• pp.120-124
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• 2000

Diltiazem inhibits calcium channels and leads to vascular smooth muscle relaxation and negative inotroic and chronotropic effects in the heart. Diltiazem (DTZ) is almost completely absorbed after oral administration, but its bioavailability is reduced because of considerable hepatic first-pass metabolism. The main metabolite of DTZ is deacetyldiltiazem. The purpose of this study was to report the pharmacokinetic changes of DTZ and its metabolite, deacetyldiltiazem (DAD) after intravenous administration of diltiazem to control rabbits and rabbits with mild and medium folate-induced renal failure (FIRRs). The area under the plasma concentration-time curves (AUC) of DTZ were significantly increased in mild and medium FIRRs. The metabolite ratio of the DAD to DTZ were significantly decreased in mild and medium FIRRs. The elimination rate constant $(\beta)$ and total body clearances (CLt) of DTZ were significantly decreased in mild and medium FIRRS. These findings suggest that the hepatic metabolism of diltiazem was inhibited and CLt and ${\beta}$ of DTZ were significantly decreased in mild and in rabbits with medium folate-induced renal failure.

• Clinical and Experimental Pediatrics
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• v.56 no.5
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• pp.196-201
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• 2013

Fluoroquinolones are an important class of antibiotics that are widely used in adult patients because of their broad spectrum of activity, good tissue penetration, and oral bioavailability. However, fluoroquinolone use in children is limited because juvenile animals developed arthropathy in previous experiments on fluoroquinolone use. Indications for fluoroquinolone use in patients younger than 18 years, as stated by the U.S. Food and Drug Administration, include treatment of complicated urinary tract infections and postexposure treatment for inhalation anthrax. In Korea, the systemic use of fluoroquinolones has not been approved in children younger than 18 years. Although concerns remain regarding the adverse musculoskeletal effects of fluoroquinolones in children, their use in the pediatric population has increased in many circumstances. While pediatricians should be aware of the indications and adverse effects of fluoroquinolones, recent studies have shown that the risk for musculoskeletal complications in children did not significantly increase following fluoroquinolone treatment. In addition, fluoroquinolones may be particularly helpful in treating multidrug-resistant infections that have not responded to standard antibiotic therapy in immunocompromised patients. In the present article, we provide an updated review on the safety and current recommendations for using fluoroquinolones in children.

• Biomolecules & Therapeutics
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• v.22 no.1
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• pp.78-81
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• 2014

Irinotecan suppository was prepared using the moulding method with a homogeneous blend. A sensitive and specific fluorescence method was developed and validated for the determination of irinotecan in plasma using HPLC. The pharmacokinetics of intravenous administered and rectal administered in rabbits was investigated. Following a single intravenous dose of irinotecan (50 mg/kg), the plasma irinotecan concentration demonstrated a bi-exponential decay, with a rapid decline over 15 min. $C_{max}$, $t_{1/2}$, $AUC_{0-30h}$ and $AUC_{0-{\infty}}$ were $16.1{\pm}2.7g/ml$, $7.6{\pm}1.2h$, $71.3{\pm}8.8{\mu}g{\cdot}h/ml$ and $82.3{\pm}9.5{\mu}g{\cdot}h/ml$, respectively. Following rectal administration of 100 mg/kg irinotecan, the plasma irinotecan concentration reached a peak of $5.3{\pm}2.5{\mu}g/ml$ at 4 h. The $AUC_{0-30h}$ and $AUC_{0-{\infty}}$ were $32.2{\pm}6.2{\mu}g{\cdot}h/ml$ and $41.6{\pm}7.2{\mu}g{\cdot}h/ml$, respectively. It representing ~50.6% of the absolute bioavailability.

• YAKHAK HOEJI
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• v.45 no.6
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• pp.634-640
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• 2001

Ibuprofen is one of the nonsteroidal anti-inflammatory drugs (NSAID) and has shown antiinflammatory; antipyretic, and analgesic activity in both animals and humans. But it causes gastric mucosal abnormalities including edema, erythema, and submucosal petechial hemorrhages and erosin in human. In addition, based on the pharmaceutical point of view the compression and dissolution ability of ibuprofen is known as poor. Therefore we studied to develop novel formulation containing water-insoluble drug, ibuprofen, using microemulsion consisting of surfactant, oil phase, and water phase was prepared for the purpose of increasing its bioavilability The physicochemical properties such as particle size, dissolution rate, solubility of ibuprofen in the system were determined. After oral administration of ibuprofen containing the microemulsion system, to Sprague-Dawley rats, pharmacokinetic parameters were also obtained. For the formulation in the study, oleic acid, linoleic acid, and several kinds of glycerides and triglycerides were used as an oil phase with several surfactants. Diethylene glycol monoethyl ether (Transcuto $l^{ }$) or saturated polyglycolized glycerides (Labrafil $^{ }$)as surfactant was used, the domain of microemulsion was wide. The diameter of o/w microemulsion was ranged from 90 to 220 nm. Microemulsion, prepared with unsatulated polyglycolized glycerides (Labrafil $^{ }$) and the 2 : 1 molar mixture of diethylene glycol monoethyl ether (Transcuto $l^{ }$)/polyoxyethylene(4) lauryl ether (Bri $j^{ }$ 30) , is expected to be promising system that increased the bioavilability of ibuprofen.ibuprofen.

• Bulletin of the Korean Chemical Society
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• v.35 no.1
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• pp.250-252
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• 2014

Lipoprotein-associated phospholipase A2 (Lp-$PLA_2$) is a crucial enzyme in atherosclerosis as a potential drug target. The most remarkable Lp-$PLA_2$ inhibitory drug is Darapladib. We determined the binding pose of Darapladib to Lp-$PLA_2$ through docking study. Darapladib formed two hydrogen bonding interactions with the side chain of Tyr160 and Gln352 and several pi-pi interactions with aromatic and aliphatic hydrophobic residues of Lp-$PLA_2$. It is known that the dietylpropan-amine moiety of Darapladib has influence on the improvement of its oral bioavailability and we supposed this in our docking results.

• Archives of Pharmacal Research
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• v.18 no.1
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• pp.22-26
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• 1995

The solubility and dissolution rate of naproxen (NPX) complexed with 2-hydroxypropyl-.betha.-cyc-lodextrin (2-HP.betha.CD) using coprecipitation, evaporation, freeze-drying and kneading method were investigated. Solubility of NPX linearly increased (correlation cefficient, 0.995) as $2-HP\betaCD$ concentraction increased, resutling in $A_l$ type phase solubility curve. Inclusion complexes prepared by four different methods were compared by different methods were compared by dfferential scanning calorimetry(DSC). The NPX showed sharp endothemic peak around $156^{\circ}C$ but inclusion complexes by evaporation, freeze-drying and kneading method showed very broad peak without distinct phase transtion temperature. In contrast, inclusion complex prepared by coprecipitation method resulted in detectable peak around $156^{\circ}C$ which is similar to NPX, suggesting incoplete formation of indusion co plex. Dissolution rate of inclusion complexes prepared by evaporation, frezz-drying and kneding except coprecipitation method was largely enhanced in the simultaed gastric and intestinal fluid when compared to NPX powder and commercial $NA-XEN^\registered$tablet. However, about 65% of NPX in gstric fluid. in case of inclusion complex prepared by coprecipitation method, formation of inclusion complex appeared to be incoplete, resulting in no marked enhancement of dissolution rate. From these findings, inclusion complexes of poorly water-soluble NPX with $2-HP\betaCD$ were useful to increase soubility and dissolution rate, resting in enhancement of bioavailability and minimization of gastrointestinal toxicity of drug upon oral administration of inclusion complex.

• Archives of Pharmacal Research
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• v.17 no.6
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• pp.428-433
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• 1994

The methabolism and phamacokinetics of a mixed disulfide S-(N, N-diethyldithiocarbamoyl)-N-acetyl-L-cysteine (AC-DDTC) were studied in rats. Two metabolites of AC-DDTC following iv and po administration were indentified in plasma and liver by HPLC and GC, namely N, N-diethyldithiocarbamate (DDTC) and the methyl ester of DDTC (Me-DDTC). AC-DDTC was very unstable in vivo and could not be detected neither in plasma nor in urine. Pharmacokinetic parameters of DDTC following intravenous administration of AC-DDTC (20 mg/kg) were calculated. DDTC has a low affinity to rat tissue and the body clearance was $9.0{\pm}3.4mkl/mim/kg$. The mean residence time (MRT) was $11.5{\pm}16.3 min$. After oral administration of 20 mg/kg AC-DDTC, maximal plasma concenttion ($C_{max}$) was $3.8{\pm}0.2 nmol/ml$ and the bioavailability was 7.04%. $C_{max}$ for DDTC at a dose of 120 mg/kg. AC-DDTC was $40.1{\pm}2.2 nmol/ml$. ART was $47.1{\pm}2.8min$.at a dose of 20 mg/kg and $110.5{\pm}6.0 min$ at 120 mg/kg.

• Archives of Pharmacal Research
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• v.28 no.8
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• pp.977-982
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• 2005

The aim of this study was to compare two formulations of film-coated pellets containing c1arithromycin after single oral dose study in healthy male volunteers. Two formulations with different coating polymers were prepared: formulation-1 (F-1) was prepared by incorporating three kinds of pH-dependent gradient-release coated pellets into capsules and formulation-2 (F-2) was prepared by coated with an insoluble semiosmotic film. Release profiles of filmcoated pellets were evaluated using paddle method under different conditions. Pharmacokinetic profiles of these formulations were obtained in three healthy male volunteers and compared to commercially available immediate release (IR) tablets. The relative bioavailability based on the $AUC_{0-24h}$ was found to be $96.2\%\;and\;58.7\%$ for F-1 and F-2 compared with IR, and the $T_{max}$ was delayed.

• Archives of Pharmacal Research
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• v.19 no.3
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• pp.246-247
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• 1996

In the previous reports (Park et al., 1991, and 1993), we described the synthesis and analgesic effects of various homovanillic amides as analogs of capsaicin. In the study, we tried to enhance the analgesic actvity of capsaicin by structural modification. Our study has been performed in three directions. First, the amide bond of capsaicin was transposed. Second, a phenyl ring was introduced to replace a double bond of capsaicin. Finally, aminoethylation was performed on 4-hydroxy group of capsaicin to improve oral bioavailability. These studies have led to N-(3-phenylpropyl)homovanillic amide 2 which has high analgesic activity. Our continuing efforts in this area have focused on the introduction of various substituents on the phenyl ring of 2 as well as their pharmacological studies. We report herein the synthesis of homovanillic amide derivatives and their analgesic activity.