• Archives of Pharmacal Research
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• v.20 no.4
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• pp.318-323
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• 1997

The experimental hepatic cirrhosis was induced either by bile duct ligation (BDL) or by pretreatment with dimethyinitrosamine (DMNA). The pharmacokinetics of theophylline were studied after a single intravenous or a single oral administration. Using the ultrafiltration method, protein-drug binding experiments were also carried out. The bilirubin level was several-fold increased by BDL, but not by DMNA treatment. The albumin content was decreased in both cirrhotic groups. The total clearance (Clt, ml/kg/hr) of theophylline in both hepatic cirrhosis groups significantly decreased and the terminal half-life $(t_{1/2})$ in the cirrhotic rats was increased about two-fold after intravenous and oral administration. The volume of distribution at steady state (Vdss, ml/kg) was increased slightly in the cirrhotic groups. Protein binding in BDL $(8.67{\pm}4.85%)$ decreased about four-folds, but in DMNA $(73.00{\pm}9.85%)$ similar result war observed as compared with the control. Increased free fraction of theophylline did not increase the volume of distribution in BDL. Therefore decreased total body clearance of theophylline was mainly due to decreased intrinsic clearance of theophylline in the liver. The absolute bioavailability of theophylline in these experiments was between 63.8 and 72.8%(66.1% in BDL, 63.8% in Sham operated and Control, 72.8% in DMNA). These results suggest that in the experimental hepatic cirrhosis model, administration route does not affect the disposition of theophylline.

• Archives of Pharmacal Research
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• v.23 no.4
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• pp.374-380
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• 2000

Propentofylline (PPF, 3-methyl-1-(5-oxohexyl)-7-propylxanthine) has been reported to be a compound for treatment of both vascular dementia and dementia of the Alzheimer type. The short half-life (about 15 min) of PPF at the terminal elimination phase and poor bioavailability after oral administration of PPF to rabbits (Kim et al., 1992) suggest in part that this drug takes the extensive first-pass metabolism in the liver. In addition, the metabolic pathway for PPF remains unclear. The objective of this experiment is to identify urinary metabolites of PPF in rats. For the identification of the metabolites, rat urine was collected after oral administration of 100${m}g/kg$ PPF. PPF metabolite, 3-methyl-1-(5-hydroxyhexyl)-7-propylxanthine, was synthesized and confirmed by gas chromatography/mass spectroscopy (GC/MS) and $^1H$ nuclear magnetic resonance spectroscopy. The urinary metabolites of PPF were extracted with diethyl ether and identified by electron impact and chemical ionization GC/MS. One urinary metabolite was confirmed to be 3-methyl-1-(5-hydroxyhexyl)-7-propylxanthine by synthesized authentic compound. Several metabolites of monohydroxy- and dihydroxy-PPF were identified based on mass fragmentation of both intact and trimethylsilylated derivatives of PPF metabolites and the novel structure of these metabolites is suggested based on mass spectra.

• YAKHAK HOEJI
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• v.47 no.2
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• pp.120-124
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• 2003

Due to its profound intestinal first-pass metabolism, oral eperisone hydrochloride produces a very low bioavailability and a very short muscle relaxant activity. To improve the efficacy and compliance of eperisone, we designed a new dosage form, the transdermal patch and evaluated the muscle relaxant effects of this patch in rats. The muscle relaxant activity was assessed by measurement of forelimb grip strength and hanging test in rats. The transdermal patch of eperisone hydrochloride showed significant muscle relaxant activity at 0.5, 1.5 and 3 cm$^2$/200 g rat (1.39, 4.17 and 8.33 mg of eperisone hydrochloride/kg, respectively) in a dose-dependent manner and the effects were lasted over 24 hours. The oral eperisone hydrochloride showed significant activity at 12.5, 25 and 50 mg/kg in a dose-dependent manner but the activity was within 1 or 2 hours after administration. These results suggest that the eperisone hydrochloride is absorbed efficiently from transdermal patch and the patch can exert potent and long-lasting muscle relaxant activity. This transdermal patch will increase the efficacy and compliance in the clinical use of eperisone hydrochloride.

• Journal of Hospice and Palliative Care
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• v.26 no.1
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• pp.18-21
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• 2023

The combination of oxycodone and naloxone is useful for cancer pain management. Naloxone, as a pure opioid antagonist, cannot be used simultaneously with opioids. However, owing to its low bioavailability, it can be used in an oral composite formulation. We present the case of a 55-year-old man with gastric cancer who experienced severe opioid withdrawal syndrome (OWS) triggered by oxycodone/naloxone that was successfully managed with dexmedetomidine. He had been in a stable condition on intravenous morphine to alleviate cancer pain. Intravenous morphine was switched to oral oxycodone/naloxone for discharge from the hospital. The patient suddenly developed restlessness, heartburn, and violent behavior 30 minutes after taking oxycodone/naloxone. We attempted sedation with midazolam and propofol, but paradoxical agitation and desaturation occurred. Next, we tried dexmedetomidine and the patient showed a decreased heart rate and reduced agitation. The patient was eventually stabilized by increasing the dose of dexmedetomidine. This report informs clinicians of the possibility of OWS when switching from opioids to oxycodone/naloxone, which can be overcome with the appropriate use of sedatives and dexmedetomidine depending on the patient's condition.

• Journal of Ginseng Research
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• v.48 no.3
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• pp.253-265
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• 2024

Orally administered ginsenosides, the major active components of ginseng, have been shown to be biotransformed into a number of metabolites by gastric juice, digestive and bacterial enzymes in the gastrointestinal tract and also in the liver. Attention is brought to pharmacokinetic studies of ginseng that need further clarification to better understand the safety and possible active mechanism for clinical application. Experimental results demonstrated that ginsenoside metabolites play an important role in the pharmacokinetic properties such as drug metabolizing enzymes and drug transporters, thereby can be applied as a metabolic modulator. Very few are known on the possibility of the consistency of detected ginsenosides with real active metabolites if taken the recommended dose of ginseng, but they have been found to act on the pharmacokinetic key factors in any clinical trial, affecting oral bioavailability. Since ginseng is increasingly being taken in a manner more often associated with prescription medicines, ginseng and drug interactions have been also reviewed. Considering the extensive oral administration of ginseng, the aim of this review is to provide a comprehensive overview and perspectives of recent studies on the pharmacokinetic properties of ginsenosides such as deglycosylation, absorption, metabolizing enzymes and transporters, together with ginsenoside and drug interactions.

• Korean Journal of Food Science and Technology
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• v.41 no.1
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• pp.106-110
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• 2009

In order to reduce the bitter taste and improve the bioavailability of red ginseng extract(RGE), inclusion complexes (RGE-CD) of the extract with ${\alpha}-,\;{\beta}-,\;{\gamma}$-cyclodextrin were prepared and studied for their sensory quality and bioavailability compared to RGE. By complexation, the bitter taste-reducing efficacies of ${\alpha}$-CD and ${\beta}$-CD were much lower than that of ${\gamma}$-CD. In comparative sensory analysis for the bitter taste, RGE-${\gamma}$-CD10, prepared using 10%(w/w) of ${\gamma}$-CD, showed a score of 1.93(decreased by about 78%) compared to RGE as the control. In addition, in sensory analysis for flavor, RGE-${\gamma}$-CD10showed a score of 5.60. Upon increasing the amount of ${\gamma}$-CD to 15%(w/w) and 20%(w/w), respectively, the bitter taste of RGE-${\gamma}$-CD was removed and the flavor of RGE disappeared(scores of 2.67 and 1.67, respectively). Therefore RGE-${\gamma}$-CD10 was chosen as an optimum. The same dosages of RGE and RGE-${\gamma}$-CD10 were orally administered to SD(Sprague-Dawley) rats on a saponin basis, and the plasma concentrations of ginsenoside Rg1 and Rb1 were measured over time to estimate the average AUC(area under the plasma concentration versus time curve) of the ginsenosides. After the oral administration, there were no significant differences in the AUC values of the RGE and RGE-${\gamma}$-CD 10 groups for ginsenoside Rg1. However, AUC values for ginsenoside Rb1 were $25.8{\mu}g{\cdot}hr/mL$ in the RGE group and $81.5{\mu}g{\cdot}hr/mL$ in the RGE-${\gamma}$-CD 10 group, respectively. Therefore, the bioavailability of ginsenoside Rb1 in the RGE-${\gamma}$-CD 10 group was significantly higher by up to 315% compared with that in the RGE group(p = 0.0029). These results show that the bitter taste of RGE can be simultaneously removed by the complexation of RGE and ${\gamma}$-CD(RGE-${\gamma}$-CD) along with increased bioavailability.

• Journal of Pharmaceutical Investigation
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• v.40 no.spc
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• pp.103-112
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• 2010

Pellets, which are multiple-unit dosage systems, have the several therapeutic advantages over single-unit dosage systems in oral drug delivery. This review focuses on the current status and explores extrusion-spheronization technique with special attention to controlled-release application of pellets including coated pellets for delayed release formulations, coated pellets for colon delivery, coated pellets for sustained drug delivery, sustained-release matrix pellets, pellets compressed into tablets, bioadhesive pellets, floating pellets, and pelletization with solubilization techniques.

• Journal of Pharmaceutical Investigation
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• v.10 no.3
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• pp.20-26
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• 1980

The purpose of this paper was to study the effect of sulpyrin on the absorption, excretion, metabolism, and protein binding of ampicillin in the small intestine of the rats and rabbits. The results are as follows; The absorption of ampicillin in small intestine of rats was increased by the combination of sulpyrin and ampicillin. The blood level of ampicillin in rabbits was elevated by oral administration of sulpyrin. The bioavailability of ampicillin was increased by simultaneous administration of sulpyrin and ampicillin. The urinary excretion of ampicillin was slightly decreased by combined administration of sulpyrin. The blood level of ampicillin was decreased and the urinary excretion was increased by long term administration of sulpyrin. On the other hand, metabolising enzyme of ampicillin was influenced by long term administration of sulpyrin. Protein binding rate of ampicillin was decreased by combination of sulpyrin as compared with control.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.285-285
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• 1996

Cyclosporin A (CyA) is widely used in the inhibition of graft rejection in organ transplantation. However, the bioavailability of CyA after oral administration is very low due to its poor solubility and dispersability hi water. To improve the solubility of CyA, microemulsion systems were developed and its physicochemical characteristics were evaluated by phase studies, solubility and dispersability tests. Phase studies on the systems composed of ethyl oleate (EO), PPG-20 methyl glucose ether (GP-20), poloxamer 123 (PL) and water U) were carried out to make stable w/o emulsions. Besides, based on CyA solubility test in various compositions of surfactant systems, a reasonable surfactant composition (GP-20/PL=4/1) was selected to enhance its solubility.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.04a
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• pp.57-63
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• 1997

Animal and clinical investigations have shown that fluoroquinolones, new quinolone antibacterial agents (NQs), are well absorbed across the intestinal tract, with a bioavailability of 60-90% after oral administration. Although some types of carrier-mediated intestinal transport mechanisms have been reported for enoxacin (ENX), ofloxacin (OFLX) and sparfloxacin (SPFX), recent results using a human intestinal epithelial cell line, Caco-2, indicated a passive or nonsaturable transport of SPFX, one of the most hydrophobic NQs. The mechanism underlying the intestinal absorption of NQs is still largely unknown. The distribution of NQs into peripheral tissues including erythrocytes is very rapid and their tissue-to-plasma concentration ratios (Kp) are considerably larger than those of inulin (an extracellular fluid space marker), in spite of almost complete ionization of NQs at the physiological pH. Our findings suggest that OFLX and lomefloxacin (LFLX) are taken up by rat erythrocytes via a transport system common to that of a water-soluble vitamin, nicotinic acid.