• The Korean Journal of Physiology and Pharmacology
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• v.22 no.3
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• pp.321-329
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• 2018

It was recently reported that the $C_{max}$ and AUC of rosuvastatin increases when it is coadministered with telmisartan and cyclosporine. Rosuvastatin is known to be a substrate of OATP1B1, OATP1B3, NTCP, and BCRP transporters. The aim of this study was to explore the mechanism of the interactions between rosuvastatin and two perpetrators, telmisartan and cyclosporine. Published (cyclosporine) or newly developed (telmisartan) PBPK models were used to this end. The rosuvastatin model in Simcyp (version 15)'s drug library was modified to reflect racial differences in rosuvastatin exposure. In the telmisartan-rosuvastatin case, simulated rosuvastatin $C_{maxI}/C_{max}$ and $AUC_I/AUC$ (with/without telmisartan) ratios were 1.92 and 1.14, respectively, and the $T_{max}$ changed from 3.35 h to 1.40 h with coadministration of telmisartan, which were consistent with the aforementioned report ($C_{maxI}/C_{max}$: 2.01, $AUC_I/AUC$:1.18, $T_{max}:5h{\rightarrow}0.75h$). In the next case of cyclosporine-rosuvastatin, the simulated rosuvastatin $C_{maxI}/C_{max}$ and $AUC_I/AUC$ (with/without cyclosporine) ratios were 3.29 and 1.30, respectively. The decrease in the $CL_{int,BCRP,intestine}$ of rosuvastatin by telmisartan and cyclosporine in the PBPK model was pivotal to reproducing this finding in Simcyp. Our PBPK model demonstrated that the major causes of increase in rosuvastatin exposure are mediated by intestinal BCRP (rosuvastatin-telmisartan interaction) or by both of BCRP and OATP1B1/3 (rosuvastatin-cyclosporine interaction).

• Journal of Soil and Groundwater Environment
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• v.9 no.1
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• pp.12-27
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• 2004

The contamination pattern of indoor air was simulated when groundwater dissolving benzene was used for household activities. Indoor exposure scenario consisted of inhalation, ingestion, and dermal absorption. Physiologically based pharmacokinetic (PBPK) model was used to analyze how benzene exposed to human body was distributed in internal organs. Main exposure pathways contributing total internal dose were inhalation and ingestion while the contribution of dermal absorption was very small. Man showed higher exposure rate than woman due to his higher breath rate. For a short-term exposure, benzene concentration in venous blood of SPT, RPT and liver changed rapidly while slowly did in venous blood of adipose tissue at a low concentration. For a long-term exposure, woman accumulated about 2.1 times higher than man. Most of benzene exposed to human body was removed by exhalation and metabolism at lung and liver, respectively. For inhalation and ingestion, the benzene removals by exhalation were 69.8 and 48.4%, respectively. Relative importance of removal mechanism was different according to the inflow displacement of benzene. The results obtained from this study would help understand exposure, distribution, and removal phenomena and make plans for the reduction of the health risk associated with the contaminated groundwater by various organic compounds.

• Journal of Food Hygiene and Safety
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• v.24 no.4
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• pp.378-384
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• 2009

There are differences of Cadmium (Cd) urinary concentration which is considered as indicator of renal tubular dysfunction in other countries, so we have reviewed domestic epidemiological data and suggested Korean health based guidance value (HBGV) for Cd to improve an efficiency of risk management. We decided to apply the WHO calculation model which considered the relationship between dietary intake and Cd concentration in urine sample. It is determined that Cd concentration 2.5 ug/g creatinine in urine as the prevalence of renal tubular dysfunction based on epidemiological data, because there is no renal tubular dysfunction and injury/lesion such as proteinuria at the concentration of 11.63 ug/g creatinine which is the highest Cd concentration in urine from the domestic epidemiological data. It is identified that the ratio between the Cd dietary consumption (8.3~10.4 ug/day) and Cd urinary concentration (0.38 ug/g creatinine) in Korean adult who predicting never been exposed to Cd are 21.8~27.3 and then it is applied to the corresponding model suggested by WHO. Also it is applied that 10% of bioavailability and 50% of excretion rate of absorbed to body (the ratio is 24) were assumed. The estimate of daily Cd consumption level which begins tubular dysfunction is 1 ug/kg bw/day, so we suggest the Korean provisional tolerable weekly intake (PTWI) as 7 ug/kg bw/week.