• 대한예방한의학회지
• /
• 제20권2호
• /
• pp.97-109
• /
• 2016

Objectives : The effects of Jaeumkanghwatang (JEKHT) co-administration on the pharmacokinetics of tamoxifen were observed after oral combination treatment of tamoxifen 50 mg/kg with JEKHT 100 mg/kg on JEKHT 6-day repeated oral pretreated rats with 8-day repeated co-administration to confirm the effects of JEKHT co-administration on the pharmacokinetics of tamoxifen. Methods : Six days after pretreatment of JEKHT 100 mg/kg, tamoxifen 50 mg/kg was co-administered with JEKHT 100 mg/kg, once a day for 8 days within 5 min. The blood were collected at 30 min before administration, 30 min, 1, 2, 3, 4, 6, 8 and 24 hrs after end of first and last 8th tamoxifen treatment, and plasma concentrations of tamoxifen were analyzed using LC-MS/MS methods. PK parameters of tamoxifen ($T_{max}$, $C_{max}$, AUC, $t_{1/2}$ and $MRT_{inf}$) were analysis as compared with tamoxifen single administered. Results : Six-day repeated oral pretreatment of JEKHT and 8-day repeated oral co-administration of tamoxifen within 5 min did not influenced on the plasma concentrations and pharmacokinetic parameters of tamoxifen, oral bioavailability, as compared with tamoxifen single treated rats, except for some negligible effects. Conclusions : It is concluded that JEKHT did not influenced on the plasma concentrations and pharmacokinetic parameters, the oral bioavailability of tamoxifen. Therefore, it is considered that co-administration of JEKHT and tamoxifen will be provide an effective novel treatment regimen on the comprehensive and integrative medicine for breast cancer patients, if they showed favorable synergic effects on the pharmacodynamics or reduce the tamoxifen treatment related toxicity and side effects in future studies.

• Journal of Pharmaceutical Investigation
• /
• 제38권4호
• /
• pp.235-240
• /
• 2008

A sensitive and simple method of determining the plasma levofloxacin (LFX, CAS 100986-85-4) concentrations in human volunteers by liquid-liquid extraction were developed and validated by using a high-performance liquid chromatography/diode array detector. The method was also applied to pharmacokinetic study of LFX. LFX was orally administered to 8 healthy male Korean volunteers at single lowest dose of 200 mg, compared to the published reports in which more than 500 mg of LFX was orally administered. LFX in human plasma was determined. The detection limit of LFX was $0.05\;{\mu}g/mL$. $C_{max}$ value was $2.48{\pm}0.67\;{\mu}g/mL$. $AUC_{0{\to}24\;hr$} and $AUC_{0{\to}{\infty}}$ were $14.52{\pm}3.35\;{\mu}g/mL$ and $16.00{\pm}3.66\;{\mu}g{\cdot}hr/mL$, respectively. The terminal half-life was $6.87{\pm}0.46\;hr$. Our pharmacokinetic parameters were very consistent with that previously reported, showing good correlation between LFX doses and AUC ($r^2=0.995$). This method can be useful for the pharmacokinetics and bioequivalence study with relatively low dose for reducing the main side effects of LFX.

• Journal of Pharmaceutical Investigation
• /
• 제35권5호
• /
• pp.383-388
• /
• 2005

A simple and specific method for determination of methyltestosterone (MT) has been established by a gas chromatography/mass selective detector and applied in plasma of healthy male volunteers received a single oral dose of 50 mg MT $(Testo^{TM}\;tablets,\;25\;mg)$ for bioavailability test. This method involves using liquid-liquid extraction of the sample with diethyl ether and derivatization with MSTFA. MT showed good resolution in this condition. The detection limit of quantitation was 5 ng/ml. A good linearity (r>0.996) was obtained at the range of 5-250 ng/ml of MT. Intra-day precision and accuracy were 2.76-12.56% and 0.39-8.01 %, and inter-day precision and accuracy were 2.29-17.69% and 0.42-7.99%, respectively. The established method was applied on bioavailability test of MT in human volunteers. The value of $AUC_{0\;to\;last}$ to last was $264.5{\pm}123.9\;ng{\cdot}hr/ml$ and that of $AUC_{0\;to\;inf}$ was determined to be $275.2{\pm}126.5\;ng{\cdot}hr/ml$. The values of $C_{max}$ and $T_{max}$ were $95.9{\pm}67.1\;ng/ml$ and $1.13{\pm}0.9\;hr$, respectively. The mean elimination half-life $(t_{1/2})$ was $4.4{\pm}0.9\;hr$. This analytical method is suitable and useful for the pharmacokinetics and bioequivalence studies of MT.

• 대한예방한의학회지
• /
• 제19권1호
• /
• pp.145-159
• /
• 2015

Objective : In the previous study, co-administration of Gongjindan-gamibang (GJD) with sorafenib increased oral bioavailability of sorafenib through augment the absorption, therefore, the effects of GJD co-administration on the pharmacokinetics of sorafenib were observed after single and 7-day repeated oral co-administration with 3.5 hr-intervals in the present study. Method : After 50 mg/kg of sorafenib treatment, GJD 100 mg/kg was administered with 3.5 hr-intervals. The plasma were collected at 30 min before administration, 30 min, 1, 2, 3, 4, 6, 8 and 24 hrs after end of first and last 7th sorafenib treatment, and plasma concentrations of sorafenib were analyzed using LC-MS/MS methods. PK parameters of sorafenib ($T_{max}$, $C_{max}$, AUC, $t_{1/2}$ and $MRT_{inf}$) were analysis as compared with sorafenib single administered rats. Results : GJD markedly inhibited the absorption of sorafenib, from 1 hr to 24 hrs after end of first 3.5 hr-interval co-administration, the $C_{max}$ (-43.27%), $AUC_{0-t}$ (-56.29%) and $AUC_{0-inf}$ (-66.70%) of sorafenib in co-administered rats were dramatically decreased as compared with sorafenib single treated rats. However, GJD significantly increased the absorption of sorafenib, from 4 hr to 8 hrs after end of last 7th 3.5 hr-interval co-administration, the $AUC_{0-t}$ (34.08%) and $AUC_{0-inf}$ (37.31%) of sorafenib in co-administered rats were dramatically increased as compared with sorafenib single treated rats. Conclusion : Although GJD decreased the oral bioavailability of sorafenib through inhibition of gastrointestinal absorptions after end of first 3.5 hr-interval co-administration, it is observed that GJD increases the oral bioavailability of sorafenib as facilitated the absorption after end of last 7th repeated co-administration. Hence, the co-administration of GJD and sorafenib should be avoided in the combination therapy of sorafenib with GJD on anticancer therapy.

• 대한예방한의학회지
• /
• 제17권2호
• /
• pp.139-155
• /
• 2013

Purpose : This study was aim to evaluate effects of pharmacodynamics and toxicity in combination therapy of donepezil with Gongjindan. The effects of Gongjindan co-administration on the pharmacokinetics (PK) of donepezil were observed after single and 7-day repeated oral co-administration with 1.5hr-intervals, to evaluate synergic pharmacodynamics and reduce toxicity of combination therapy of donepezil with Gongjindan. Materials and Methods : After 10mg/kg of donepezil treatment, Gongjindan100mg/kg was administered with 1.5hr-intervals. The plasma were collected at 30min before administration, 30min, 1, 2, 3, 4, 6, 8 and 24hrs after end of first and last 7th donepezil treatment, and plasma concentrations of donepezil were analyzed using LC-MS/MS methods. Results : Gongjindan markedly inhibited the absorption of donepezilregardless of sample time, from 30min to 8hrs after end of first 1.5hr-interval co-administration as compared with donepezil single treated rats. Especially the absorption of donepezil was significantly decreased at 2, 4, 6 and 8hrs after co-administration as compared with donepezilsingle treated rats. Accordingly, the Cmax (-26.236%), $AUC_{0-t}$(-26.02%) and $AUC_{0-inf}$(-25.90%) of donepezil in 1.5hr-interval co-administered rats were dramatically decreased as compared with donepezilsingle treated rats, respectively. However, no meaningful changes on the plasma donepezil concentrations and pharmacokinetic parameters were detected after end of last 7th 1.5hr-interval co-administration as compared with donerezil single treated rats, except for non-significant slight increases of Tmax(16.67%) detected in co-administered rats as compared with donepezil single treated rats. Conclusion : These findings are considered as direct evidences that Gongjindan also decreased oral bioavailability of donerezil as inhibited the absorptions, when they were co-administered with 1.5hr-intervals, but they may be adapted after 7 days continuous repeated l.5hr-interval co-administration.

• 대한예방한의학회지
• /
• 제21권2호
• /
• pp.127-137
• /
• 2017

Objectives : In our previous study, single co-administration GMODT within 5 min significantly inhibited the oral bioavailability of tamoxifen through variable influences on the absorption and excretion of tamoxifen. Therefore, the object of this study was to elucidate the possible effects on the pharmacokinetics of tamoxifen after single oral co-administration of GMODT with 2.5 hr-intervals. Methods : After 50 mg/kg of tamoxifen treatment, GMODT 100 mg/kg was administered with 2.5 hr-intervals. The plasma were collected at 30 min before administration, 30 min, 1, 2, 3, 4, 6, 8 and 24 hrs after end of GMODT treatment, and plasma concentrations of tamoxifen were analyzed using LC-MS/MS methods. PK parameters of tamoxifen (Tmax, Cmax, AUC, $t_{1/2}$ and $MRT_{inf}$) were analysis as compared with tamoxifen single administered rats. Results : Two-half hr-interval co-administration with GMODT induced variable changes on the plasma tamoxifen concentrations as compared with tamoxifen single treated rats, and especially significant (p<0.05) increases of plasma tamoxifen concentrations were demonstrated at 0.5 (199.61%) and 1 hr (101.06%) after end of co-administration with GMODT, and also related significant (p<0.05) decreases of $t_{1/2}$ (-39.54%) and $MRT_{inf}$ (-43.94%) as compared with tamoxifen single formula treated rats, at dosage levels of tamoxifen 50 mg/kg and GMODT 100 mg/kg with 2.5 hr-intervals, in this experiment. Conclusions : According to the results, GMODT critically decreased on the oral bioavailability of tamoxifen through variable influences on the absorption and excretion of tamoxifen. Hence, the co-administration of GMODT and tamoxifen should be avoided in the comprehensive and integrative medicine, combination therapy of tamoxifen with GMODT on the breast cancer.

• 한국임상수의학회지
• /
• 제36권4호
• /
• pp.212-218
• /
• 2019

This study evaluates the drug delivery and biocompatibility of latanoprost imbedded disk in rabbit eye by assessing pharmacokinetics (PK), clinical signs, and histopathologic findings. During 84 days of experimental period, 48 New Zealand Rabbit (NZW) eyes were divided into control group which received no treatment and test material group which latanoprost were implanted intrasclerally. Pharmacokinetic assessment was performed to evaluate the drug delivery for 3 months. For biocompatibility, clinical signs were observed and histopathological analysis was done at 3 months post-operatively. The concentration of latanoprost in the iris tissue was maintained during the experimental period and the highest level of latanoprost was found at 4 weeks. However, the latanoprost was not found in the aqueous humor. Macroscopically, there was no evidence of clinical signs except for temporary hyperemia, neovascularization and edema immediately after surgery. On histopathological examination, there were no abnormal findings such as hyperemia, neovascularization, and edema in the eye tissues. The latanoprost imbedded disks has effectively released the drug into the adjacent tissue with high compatibility. Therefore, this study suggests that the drug delivery system with intrascleral latanoprost imbedded implants might be a novel approach as a treatment option for glaucoma.

• 한국어병학회지
• /
• 제35권1호
• /
• pp.93-102
• /
• 2022

본 연구에서는 뱀장어에 대한 trichlorfon (TCF)의 잔류허용기준(maximum residue level, MRL) 설정을 위한 기초 자료를 얻기 위하여 뱀장어를 대상으로 하여 trichlorfon (TCF) 노출에 따른 체내 잔류량 및 약물동태학적 분석을 실시했다. 28℃와 18℃ 에서 각각 30 ppm 및 150 ppm의 TCF를 30분간 약욕하여 이에 따른 체내 약물잔류농도를 LC-MS/MS로 분석한 결과를 바탕으로 PK solver program 을 이용하여 혈청, 근육 및 간에서 TCF의 약동학 파라미터를 얻었다. 혈청, 근육 및 간에서 최고 농도(C_max)는 25.87-357.42, 129.91-1043.73 및 40.47-375.20였고, 최고 농도 도달시간(T_max)는 0.13-1.32 h, 1.17-3.34 h, 및 0.14-5.40 h이었으며, 배설 반감기 (T_1/2)는 2.13-3.92 h, 5.30-10.35 h, 및 0.65-13.81 h이었다. 30 mg/L농도 투여군에서는 약욕 후 96시간이 지난 뱀장어의 혈청에서 TCF가 검출되지 않았으며, 근육 및 간에서는 336시간이후 부터 검출 한계 이하로 나타났다. 반면에 150 mg/L농도 투여군에서는 약욕 후 336시간이 지난 뱀장어의 혈청에서 TCF가 검출되지 않았지만, 근육 및 간에서는 336시간에도 검출되었다. 결론적으로 본 연구를 통해 얻은 결과들은 향후 양식 뱀장어에 대한 trichlorfon (TCF)의 잔류허용기준(MRL) 설정에 유용한 기초 자료로 활용 될 것으로 기대한다.

• Biomolecules & Therapeutics
• /
• 제14권1호
• /
• pp.50-55
• /
• 2006

The objective of the study was to evaluate the bioequivalency between the $Rozid^{TM}$ Tablet (Ilhwa Pharm. Co., Ltd.) as a test formulation and the $Rulid^{TM}$ Tablet (Handok Pharm. Co., Ltd) as a reference formulation. Twenty-four healthy male volunteers were administered the formulations by the randomized Latin square crossover design, and the plasma samples were determined by a high performance liquid chromatography (HPLC) with fluorescence detector. $AUC_t,\;C_{max}\;and\;T_{max}$ were obtained from the time-plasma concentration curves, and log-transformed $AUC_t\;and\;C_{max}$ and log-untransformed $T_{max}$ values for two formulations were compared by statistical tests and analysis of variation. $AUC_t$ was determined to be $63.30{\pm}25.57{\mu}g.hr/ml$ for the test formulation and $64.02{\pm}29.27mg.hr/ml$ for the reference formulation. The mean values of $C_{max}$ for the test and reference formulations were $5.07{\pm}2.14\;and\;5.53{\pm}2.60{\mu}g/ml$, respectively. The $AUC_t,\;and\;C_{max}$ ratios of the test $Rozid^{TM}$ Tablet to the reference $Rulid^{TM}$ Tablet were -1.12% and -8.32%, respectively, showing that the mean differences were satisfied the acceptance criteria within 20%. The results from analysis of variance for log-transformed $AUC_t,\;and\;C_{max}$ indicated that sequence effects between groups were not exerted and 90% confidence limits of the mean differences for $AUC_t,\;and\;C_{max}$ were located in ranges from log 0.80 and log 1.25, satisfying the acceptance criteria of the KFDA bioequivalence. The RozidTM Tablet as the test formulation was considered to be bioequivalent to the RulidTM Tablet used as its reference formulation, based on $AUC_t,\;and\;C_{max}$ values.

• Archives of Pharmacal Research
• /
• 제27권6호
• /
• pp.676-681
• /
• 2004

Acetyl-L-camitine (ALC), a naturally occurring endogenous compound, has been shown to improve the cognitive performance of patients with senile dementia Alzheimer＇s type, and to be involved in cholinergic neurotransmission. Because ALC is an endogenous compound, valida-tion of the analytical methods of ALC in the biological fluids is very important and difficult. This study was presented validation and correction for plasma ALC concentrations and pharmacok-inetics after oral administration of ALC to human volunteers. ALC concentrations in human plasma were corrected by subtracting the concentration of blank plasma from each sample. Precision and accuracy (bias %) for uncorrected ALC concentrations were below 2.6 and 6.5% for intra-days, and 4.0 and 9.4% for inter-days, respectively. Precision and accuracy (bias %)for corrected ALC concentrations were below 10.9 and 6.0% for intra-days, and 10.5 and 16.9% for inter-days, respectively. Quantitation limit was $0.1{\;}\mu\textrm{g}／mL$. After oral administration of a 500 mg ALC tablet to 8 healthy volunteers, the principle pharmacokinetic parameters were 4.2 h of the half-life$ (t_{1/2},{\beta})$, the area under the curve $(AUC_{0{\rightarrow}8){\;}of{\;}9.88{\;}\mu\textrm{g}{\cdot}h/mL$, and 3.1 h of the time ($T_{max}$) to reach $C_{max}$. This study first describes the pharmacokinetic study after oral admin-istration of a single dose of ALC in human volunteers.