• YAKHAK HOEJI
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• v.49 no.5
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• pp.399-404
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• 2005

To investigate drug interaction, 23,536 prescriptions published for 1 year were investigated with 'Drug Inter­action Fact 2002'. Dispensing records and a database file written in a local general hospital in South Korea were used as a sample. The number of total cases of drug interaction was 3,238 ($13.76\%$) out of 23,536 prescriptions. The incidence of drug interaction in each prescription the children, the adults, and the elderly were $1.33\%,\;10.97\%,\;25.50\%$, respectively. The incidences of drug interaction per each prescription were $22.03\%,\;20.52\%,\;0.51\%,\;and\;0.36\%$ in neurosurgery, internal med­icine, pediatrics, and orthopedics, respectively. In neurosurgery and internal medicine, risk-high drugs of drug interaction such as antihypertensive drugs, diuretics, and cimetidine were used very often in elderly. In this paper, several suggestions to reduce drug interaction were postulated with regard to the usage of analgesics, non-steroidal antiinflammatory drugs, and antibiotics.

• Korean Journal of Clinical Pharmacy
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• v.16 no.2
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• pp.147-154
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• 2006

Drugs are often taken together with meals and there are numerous opportunity for food-drug interaction to occure. Food-drug interactions and their clinical consequences are very complex indeed. The composition of the meal, and the volume of fluid that is ingested often are decisive factors in food-drug interactions. Various formulations of a specific drug may behave differently. Solutions and suspensions seem to be less susceptible and enteric-coated preparations are more susceptible, to food interactions than are other dosage forms but exceptions to this rule do exist. Furthermore, generic and environmental factors, disease and other drugs cause considerable inter- and intraindividual variation in food-drug interactions. Also, eating habits are dissimilar in different parts of the world, and diets often vary greatly from day to day. The taking of drugs together with meals offers some obvious benefits. It may help to reduce gastrointestinal irritation and compliance is improved. On the other hand, in some cases food interferes seriously with drug absorption. The purpose of this review is to clarify the complexity of food-drug interactions, and to discuss interactions that may be of clinical importance.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.252.2-252.2
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• 2003

It was difficult that we analysed the polymeric drugs for the physico-chemical properties. Sodium hyaluronate is a linear polysaccharide composed of repeating disaccharides of sodium glucuronate and N-acetyl glucosamine found throughout the tissues of the body with high concentrations in the vitreous humor. synovial fluid and umbilical cord. It has a role in regulating the interaction between adjoining tissues. (omitted)

• Korean Journal of Clinical Pharmacy
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• v.25 no.2
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• pp.120-129
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• 2015

Objectives: Drug utilization review program in Korea has provided 'drug combinations to avoid (DCA)' alerts to physicians and pharmacists to prevent potential adverse drug events or inappropriate drug use. Seven hundred and six DCA pairs have been announced officially by the Ministry of Food and Drug Safety (MFDS) by March, 2015. Some DCA pairs could be grouped based on the drug interaction mechanism and its consequences. This study aimed to investigate the drug-drug interaction (DDI) pairs, which may be potential DCAs, generated by the drug class-drug class interaction method. Methods: Eleven additive/synergistic and one antagonistic drug class-drug class interaction groups were identified. By combining drugs of two interacting drug class groups, numerous DDI pairs were made. The status and severity of DDI pairs were examined using Lexicomp and Micromedex. Also, the DCA listing rate was calculated. Results: Among 258 DDI pairs generated by the drug class-drug class interaction method, only 142 pairs were identified as official DCA pairs by the MFDS. One hundred and four pairs were identified as potential DCA pairs to be listed. QT prolonging agents-QT prolonging agents, triptans-ergot alkaloids, tricyclic antidepressants-monoamine oxidase inhibitors, and dopamine agonists-dopamine antagonists were identified as drug class-drug class interaction groups which have less than 50 % DCA listing rate. Conclusion: To improve the clinicians' adaptability to DCA alerts, the list of DCA pairs needs to be continuously updated.

• Mass Spectrometry Letters
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• v.13 no.3
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• pp.58-83
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• 2022

We developed analytical methods using high performance chromatography (HPLC) and liquid chromatography tandem mass spectrometry (LC-MS/MS) for the simultaneous determination of 80 unapproved compounds in dietary supplements. The target compounds for analysis were unapproved ingredients (e.g., pharmaceuticals) that have potential adverse effects on consumers owing to accidental misuse, overuse, and interaction with other medication in dietary supplement. Two analytical methods were tested to identify the optimal validation results according to AOAC guideline. As a result, limit of quantification (LOQ) was 0.14-0.5 ㎍ mL^-1; linearity (r²) was ≥ 0.99; accuracy (expressed as recovery) was 78.9-114%; precision (relative standard deviation) was ≤ 4.28% in the HPLC method. In the LC-MS/MS method, LOQ was 0.01-2 ng mL^-1, linearity (r²) was ≥0.98, accuracy was 71.7-119%; precision was ≤ 12.5%. The developed methods were applied to 51 dietary supplements collected from 2019 to 2021 through MFDS alert system. Based on our previous monitoring study, major compounds were icariin, sibutramine, yohimbine, sildenafil, tadalafil, sennosides (A, B), cascarosides (A, B, C, D), and phenolphthalein. In this study, we re-analyzed samples of detected compounds, and evaluated the statistical difference using Bland-Altman analysis to compare two analytical approaches between HPLC and LC-MS/MS. These results showed a good agreement between two methods that can be used to monitor the unapproved ingredients in dietary supplements. The developed two methods are complementarily suitable for monitoring the adulteration of 80 unapproved compounds in dietary supplements.

• Biomolecules & Therapeutics
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• v.17 no.3
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• pp.299-304
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• 2009

Rosiglitazone maleate (RGM) is widely used for improving insulin resistance. RGM is a moderate inhibitor of cytochrome P450 2C8 (CYP2C8) and is also mainly metabolized by CYP2C8. The aim of this study was to determine whether the effect of RGM on CYP2C8 is altered by co-treatment with other drugs, and whether amlodipine camsylate (AC) changes the pharmacokinetics (PK) of RGM. Of the 11 drugs that are likely to be co-administered with RGM in diabetic patients, seven drugs lowered the $IC_{50}$ value of RGM on CYP2C8 by more than 80%. In vitro CYP2C8 inhibitory assays of RGM in combination with drugs of interest showed that the $IC_{50}$ of RGM was decreased by 98.9% by AC. In a pharmacokinetic study, Sprague-Dawley (SD) rats were orally administered 1 mg/kg of RGM following by single or 10-consecutive daily administrations of 1.5 mg/kg/day of AC. No significant changes in the pharmacokinetic parameters of RGM were observed after a single administration of AC, but the AUC and $C_{max}$ values of RGM were significantly reduced by 36% and 31%, respectively, by multiple administrations of AC. In conclusion, RGM was found to be affected by AC by in vitro CYP2C8 inhibition testing, and multiple dosing of AC appreciably changed the pharmacokinetics of RGM. These findings suggest that a drug interaction exists between AC and RGM.

• Journal of Food Hygiene and Safety
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• v.32 no.2
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• pp.89-95
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• 2017

A rapid, sensitive analytical method for glucuronolactone in beverages was developed and validated using hydrophilic interaction liquid chromatography coupled to electrospray ionization tandem mass spectrometry (HILIC-ESI-MS/MS). To determine the optimum analytical conditions for glucuronolactone, three different kinds of HILIC columns and two mobile phases with different pH values were examined. An amide-bonded stationary phase with a pH 9 acetonitrile-rich mobile phase was the best condition in terms of column retention, ESI-MS/MS response area, and signal-to-noise ratio. After extraction, glucuronolactone was separated through the HILIC amide column and detected by negative ESI-MS/MS in selected reaction monitoring (SRM) mode. Nine energy drinks sold in Korea were spiked with glucuronolactone at a concentration of 5 ng/mL; the Monster $Energy^{TM}$ sample showed the smallest peak area and its signal-to-noise ratio was used for method validation. Good linearity was obtained in the concentration range from 20 to 1500 ng/mL with a correlation coefficient > 0.998. The developed method had a limit of detection (LOD) of 6 ng/mL and a limit of quantitation (LOQ) of 20 ng/mL. The recovery of this method at concentration of 20, 100, 500, and 1000 ng/mL was 96.3%-99.2% with relative standard deviations (RSD) of 1.6%-14.0%. A reproducibility precision assessment at concentration of 100 and 500 ng/mL was carried out among three laboratories. The recovery of that evaluation was 95.1%-102.3% with RSD of 2.7%-7.0%. An analysis of variance indicated that there was no difference between the recovery results of the three laboratories at the 5% significance level. The validated method is applicable to inspecting beverages adulterated with glucuronolactone in Korea.

• Biomolecules & Therapeutics
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• v.25 no.3
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• pp.288-295
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• 2017

The incidence of polypharmacy-which can result in drug-drug interactions-has increased in recent years. Drug-metabolizing enzymes and drug transporters are important polypharmacy modulators. In this study, the effects of bosentan and rifampin on the expression and activities of organic anion-transporting peptide (OATP) and cytochrome P450 (CYP450) 2C9 and CYP3A4 were investigated in vitro. HEK293 cells and primary human hepatocytes overexpressing the target genes were treated with bosentan and various concentrations of rifampin, which decreased the uptake activities of OATP transporters in a dose-dependent manner. In primary human hepatocytes, CYP2C9 and CYP3A4 gene expression and activities decreased upon treatment with $20{\mu}M$ $bosentan+200{\mu}M$ rifampin. Rifampin also reduced gene expression of OATP1B1, OATP1B3, and OATP2B1 transporter, and inhibited bosentan influx in human hepatocytes at increasing concentrations. These results confirm rifampin- and bosentan-induced interactions between OATP transporters and CYP450.

• YAKHAK HOEJI
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• v.58 no.4
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• pp.255-261
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• 2014

Poly-pharmacy has been on the rise because of aging of population and chronic disease. Most of drug metabolism happens in the liver by CYP isozymes and the metabolism by CYP450 enzymes. The Cytochrome P450 (CYP) is a superfamily of enzymes that catalyzes the oxidations of many endogenous and exogenous compounds. Primary human Hepatocytes (HH) are considered as the gold standard model for In vitro drug interaction studies. However, there are several limitations (cost, limited life span) for using HH cells. HepaRG cells are being used as a possible alternative. HepaRG cells were cultured in William E medium containing the positive control inducers (1A2: 10, 25, 50 ${\mu}M$ omeprazole, 2C9 and 2C19: 10 ${\mu}M$ rifampin, 3A4: 10, 25, 50 ${\mu}M$ rifampin) at $37^{\circ}C$, 5 % $CO_2$ in a humidified atmosphere. This study was to evaluate the induction of CYP isozymes (1A2, 2C9, 2C19 and 3A4) using LC-MS/MS. We evaluated the potential induction ability of Bosentan, as a drug of pulmonary artery hypertension, in HepaRG cells. For reference, dose of the Bosentan is determined to the basis of the $C_{max}$ (835 mg/ml) value. The enzyme activity demonstrated that CYP2C9 and 3A4 were induced up to 20 times by Bosentan. Like as In vivo, the enzyme activity of CYP2C9 and CYP3A4 is significantly induced in a dose-dependent by Bosentan.

• Journal of the Korean Society of Food Science and Nutrition
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• v.21 no.2
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• pp.219-230
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• 1992

Nutrients and drugs are similar to biological fate, such as absorption, metabolism and excretion. Such procedure may interact with nutrients and drugs. Drugs can influence nutrient absorption, metabolism or excretion ; the effects may impair the nutritional status of a patient. Specific nutrient, nutritional status, or dietary factors alter drug utilization. Therefore, medicated patients need to be aware of good nutrition practices and to understand the importance of dietary modifications associated with certain diseases. A nutritious and well balanced diet not only makes an important contribution to the health of those patients, but also reduces the risk of nutrition disorders or altered the pharmacological action of drugs.