• The Korean Journal of Pesticide Science
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• v.18 no.4
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• pp.342-349
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• 2014

Methods of establishment of AOEL (Acceptable Operator Exposure Level), application of oral absorption by country, and calculation of exposure dose for operator risk assessment in USA, EU and Korea were investigated. Oral absorption of 141 active substances for pesticides was also investigated, then operator risk assessment was conducted with AOEL including oral absorption and Korean AOEL. Internal dose converted to external dose with oral or dermal absorption in USA and EU, but external dose to which oral absorption was not applied was used for establishment of AOEL in Korea. Oral absorption of 50 active substances among 141 were below 80%. In case of application of oral absorption as a correction factor in below 80%, AOELs of about 36% active substances were considered to be lower than the current Korean AOELs. Operator risk assessment of 28 active substances among 50 active substances with oral absorption below 80% was conducted with EU AOELs. TER (Toxicity Exposure Ratio) of 12 plant protection products including chlorothalonil WG (Water-dispersible Granule) was less than 1 and the risk was high. Operator risk assessment of 24 active substances among 50 active substances with oral absorption below 80% was conducted with Korean AOELs. TER of 6 plant protection products including chlorothalonil WG were less than 1 and the risk was high. Operator risk assessment of 4 plant protection products not having Korean AOEL was conducted with converted EU AOEL into AOEL not including oral absorption. The results indicated TER of 4 products including daminozide WP (Wettable Powder) was over 1 and risk was low. 22 products except 6 products such as oxadiagyl SC (Suspension Concentration) were shown the same results of risk assessment between EU AOELs and Korean AOELs. As a result, it was considered that AOELs including oral absorption was possible to be used for operator risk assessment. It was considered operator risk assessment with AOEL including oral absorption was more like real assessment method, and improvement of assessment was needed for application to evaluate pesticides in registration.

• Bulletin of the Korean Chemical Society
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• v.32 no.11
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• pp.3967-3972
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• 2011

A whole body physiologically based pharmacokinetic (PBPK) model was applied to investigate absorption, distribution, and physiologic variations on pharmacokinetics of imatinib in human body. Previously published pharmacokinetic data of the drug after intravenous (i.v.) infusion and oral administration were simulated by the PBPK model. Oral dose absorption kinetics were analyzed by adopting a compartmental absorption and transit model in gut section. Tissue/plasma partition coefficients of drug after i.v. infusion were also used for oral administration. Sensitivity analysis of the PBPK model was carried out by taking parameters that were commonly subject to variation in human. Drug concentration in adipose tissue was found to be higher than those in other tissues, suggesting that adipose tissue plays a role as a storage tissue for the drug. Variations of metabolism in liver, body weight, and blood/plasma partition coefficient were found to be important factors affecting the plasma concentration profile of drug in human body.

• Macromolecular Research
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• v.17 no.2
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• pp.79-83
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• 2009

The oral delivery of heparin is the preferred therapy in the treatment of patients with a high risk of deep vein thrombosis and pulmonary embolism. New conjugates of heparin and sodium deoxycholate were synthesized in order to enhance the heparin absorption in the GI tract. After oral administration of DOC-heparin, the concentration in anti-FXa assay was increased with increasing amount of coupled DOC. The maximum concentration of DOC-heparin VIII conjugate was $3.3{\pm}0.5\;IU/mL$ at an oral dose of 10 mg/kg, which was 3-fold higher than the baseline level. Finally, DOC coupled to heparin greatly enhanced the absorption of heparin in the GI tract, and this enhancing effect was not induced by changing the tissue structure of the GI wall.

• Archives of Pharmacal Research
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• v.25 no.5
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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.

• Archives of Pharmacal Research
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• v.8 no.3
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• pp.177-186
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• 1985

Effect of food on the absorption characteristics of oral rifampicin was studied in the fasted rats. Rifampicin dissolved in a new cosolvent was also injected to the rats intravenously, and the pharmacokinetic analysis was performed to explain the effect of food on the gastrointestinal absorption of rifampicin. Rifampicin was absorbed rapidly and completely in the fasting state. Food had a profound effect on the gastrointestinal absorption of rifampicin, i. e., bioavailability and the extent of absorption were decreased to less than one-third of the fasting state in the postprandial state. Food seemed to imhibit the absorption and reabsorption of rifampicin in the gastrointestinal tract, but not the absorption rate constant. Hepatobiliary excretion seemed to be the major route of elimination, since the renal clearance accounted for only 8 % of the systemic clearance. Nevertheless, first-pass effect was negligibly small and most of rifampicin absorbed could reach systemic circulation. Serum concentration change of oral rifampicin on multiple dosing differed markedly in the fasting and postprandial state, which suggested the need of careful adjustment of dosage regimen in both states.

• Archives of Pharmacal Research
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• v.26 no.9
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• pp.768-772
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• 2003

Tween 80 (Polysorbate 80) is a hydrophilic nonionic surfactant commonly used as an ingredient in dosing vehicles for pre-clinical in vivo studies (e.g., pharmacokinetic studies, etc.). Tween 80 increased apical to basolateral permeability of digoxin in Caco-2 cells suggesting that Tween 80 is an in vitro inhibitor of P-gp. The overall objective of the present study was to investigate whether an inhibition of P-gp by Tween 80 can potentially influence in vivo absorption of P-gp substrates by evaluating the effect of Tween 80 on the disposition of digoxin (a model P-gp substrate with minimum metabolism) after oral administration in rats. Rats were dosed orally with digoxin (0.2 mg/kg) formulated in ethanol (40％, v/v) and saline mixture with and without Tween 80 (1 or 10％, v/v). Digoxin oral AUC increased 30 and 61％ when dosed in 1 ％ and 10％ Tween 80, respectively, compared to control (P＜0.05). To further examine whether the increase in digoxin AUC after oral administration of Tween 80 is due, in part, to a systemic inhibition of digoxin excretion in addition to an inhibition of P-gp in the GI tract, a separate group of rats received digoxin intravenously (0.2 mg/kg) and Tween 80 (10％ v/v) orally. No significant changes in digoxin IV AUC was noted when Tween 80 was administered orally. In conclusion, Tween 80 significantly increased digoxin AUC and Cmax after oral administration, and the increased AUC is likely to be due to an inhibition of P-gp in the gut (i.e., improved absorption). Therefore, Tween 80 is likely to improve systemic exposure of P-gp substrates after oral administration. Comparing AUC after oral administration with and without Tween 80 may be a viable strategy in evaluating whether oral absorption of P-gp substrates is potentially limited by P-gp in the gut.

• Journal of Food Hygiene and Safety
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• v.39 no.4
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• pp.299-303
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• 2024

Collagen, as an indicator of skin health, has been developed and used for various purposes. The development of an optimized collagen product suitable for use has become an important research field as the consumption of collagen increases. In particular, various efforts are being made to increase its absorption rate. In this study, the transdermal and oral epithelial cell permeabilities of various molecular weight collagen products sold in Korea were compared using a Franz diffusion cell system. The collagen absorption rate of oral mucosal tissue compared to skin epidermis/dermis tissue was significantly higher than that of collagen at M.W. 500 and 1,000 (approximately 10 times and 2 times higher, respectively). Additionally, collagen with a molecular weight of 500 Da increased the absorption rates by 2-3 times compared with products with a molecular weight of 1,000. Collagen with a molecular weight of 500 Da showed the highest Cmax and AUCt values, and all parameters in the oral mucosal cell test group were higher than those in the skin epidermis/dermis cells. Our findings suggest an increased absorption rate through oral mucosal cells rather than skin absorption, confirming that low molecular weight collagen is a major factor increasing the absorption rate.

• Archives of Pharmacal Research
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• v.25 no.3
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• pp.387-391
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• 2002

The oral absorption and disposition of itraconazole were studied in rats, rabbits and dogs. Serum levels of itraconazole and its active metabolite, hydroxyitraconazole, were determined by a validated HPLC method. The absorption of itraconazole was relatively rapid in rats and dogs but was slower in rabbits. The terminal elimination half-life ($T_{1/2,{\lambda}z}$), time to the peak concentration ($T_{max}$), dose and weight normalized area under the curve (AUC) and the peak concentration ($C_{max}$) of itraconazole found in the dog were comparable to those reported in humans. As in humans, the metabolite to parent drug AUC ratios in rats and dogs were greater than unity but was less in rabbits. The dog appears to be an appropriate animal model while the rat, not the rabbit, may be used as an alternative animal model in predicting the oral absorption of itraconazole in humans.

• Journal of Life Science
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• v.34 no.8
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• pp.548-557
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• 2024

Curcumin, the primary active compound in Curcumae Radix of the ginger family, exhibits a range of therapeutic effects, including blood sugar regulation, immunoregulation, antioxidant, antibacterial, and antitumor activities. However, its poor water solubility and chemical instability result in suboptimal pharmacokinetics with low oral absorption (0.18%) and bioavailability, thus limiting its efficacy. To overcome these limitations, this study aimed to enhance the oral absorption and bioavailability of curcumin by incorporating lysine and β-cyclodextrin. Following oral administration of solubilized cur- cumin, blood samples were collected to assess the oral absorption rate. Solubilized curcumin showed an approximately 1.55-fold increase in absorption at 120 min compared to its non-solubilized form. Furthermore, intravenous administration followed by blood analysis showed a 25-fold increase in bio- availability at 61 min for the solubilized curcumin compared to the non-solubilized variant. In conclusion, employing lysine for dispersion and stabilization, combined with β-cyclodextrin to enhance solubility, significantly improves curcumin's oral absorption and bioavailability. The results of this experiment are expected to lead to the development of herbal medicines and pharmaceuticals that amplify curcumin's anti-inflammatory, anti-tumor, and blood-sugar-regulation effects.

• Journal of Pharmaceutical Investigation
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• v.16 no.4
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• pp.148-151
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• 1986

This paper was designed to investigate the influence of different suppository bases on both the rectal absorption and dissolution rate of lithium carbonate, and to compare bioavailability from rectal administration with that from oral administration. The dissolution rates were in such order as PEG 4000, surfactant A (Witepsol 15+sodium lauryl sulfate), surfactant B (Witepsol 15+cholic acid), Witepsol 15 and cacao butter. Among various suppository bases, the blood level of lithium carbonate after rectal administration was increased in the following order: surfactant A>surfactant B>PEG 4000>Witepsol 15>cacao butter. When it comes to compare oral with rectal administration in AUC values, surfactants and PEG 4000 showed similar blood levels to oral administration, but lipophilic bases such as Witepsol 15 and cacao butter showed far lower blood level than oral administration. Peak time in oral administration was 2 hrs, but those in rectal administration using various suppository bases were $6{\sim}8$ hrs.