• Biomolecules & Therapeutics
• /
• v.4 no.3
• /
• pp.265-270
• /
• 1996

The purpose of this study was to determine pharmacokinetic parameters and tissue distribution patters of urinary trypsin inhibitor(UTI) in Sprague-Dawley rats. $Na^{125}$I was conjugated to UTI to make $^{125}I-UTI$ and the concentrations were determined by $\gamma$-counter. With the aid of nonlinear least-square regression analysis for i.v bolus injection of 1,000 unit UTI including $^{125}I-UTI$, the temporal concentration curves were best fitted by 2-compartment open model. The distribution phase half-life was 0.39$\pm$0.02 hours whereas the elimination half-life was 12.99$\pm$1.05 hours in male rats. The volume of distribution and total body clearance in male rats were 0.28$\pm$0.01 1/kg and 83.16$\pm$1.15 ml/kg/h, respectively. We could not find any difference of pharmacokinetic parameters of UTI between male and female rats. UTI were distributed widely in rat organs. In both male and female rats, the kidney was the highest distributed organ. Amount of UTI in 24 hour cumulative urine in male rats was 36.22$\pm$8.74% and that in 48 hours was 43.32$\pm$10.55%. Excretion via feces was very scanty, with the 24 hours cumulative amount being only 2.76$\pm$0.97%. This data suggest the main excretion route of UTI is urine.

• Archives of Pharmacal Research
• /
• v.26 no.12
• /
• pp.1096-1101
• /
• 2003

To enhance the liver targeting and reduce the side effects of 5-fluorouracil (5-Fu), it was acylated by stearyl chloride to obtain .$\b{N}_{\b{1}}$stearyl-5-Fu (5-FuS). The chemical structure of the prodrug was confirmed by Nuclear Magnetic Resonance and Infrared Spectrometry. 5-FuS was incorporated into solid lipid nanoparticles (SLN), which were prepared by the physical agglomeration method. The mean diameter of 5-FuS-SLN was 240.19 nm and the drug loading was 20.53%. The release characteristics in vitro of 5-FuS-SLN were fitted to the first-order pharmacokinetic model. Compared with 5-Fu injection, a study on the distribution of 5-FuS-SLN in mice showed that 5-FuS-SLN could double 5-Fu concentration in mice livers. The main pharmacokinetic parameters of 5-FuS-SLN in rabbits is shown as follows: $V_d$=0.04336L/kg, $T_{1/2} \beta$=1.2834h, CL=0.1632 L/h. In conclusion, 5-FuS-SLN has significant liver targeting properties. The employment of a prodrug to enhance drug liposoluble properties and the preparation method presented in this paper, seem to be an alternative strategy to the traditional colloidal delivery system.

• Archives of Pharmacal Research
• /
• v.17 no.2
• /
• pp.80-86
• /
• 1994

The bioavailability of digoxin generic tablets manufactures in Korea (formulations A & B) wwere compared to a standard (formulation C; Lanoxin brand digoxin, Burroughs Wellcome, USA) in 12 healthy Korean male volunteers (mean age 31.4 years) in a single dose, randomized, complete block crossover study. Using a latin square design, each of the subjects was randomized to the order number and allocated to each of the three treatments of 0.5mg oral digoxin. Digoxin conc4ntrations in serum and urine samples collected for 48 hours after dosing were measured by fluoprescence polarization immunoassy and radioimmunoassy, respectively. Treatments were compared by using nonlinear least squares regession analysis to evaluate the following pharmacokinetic parameters : maximum serum concentation $(C_{max})$; time of maximum serum concentation $(T_{max})$; area under the serum concentration-time curve $AUC_{0-12}$, $C_{max}$\;and\;(AUC_{0-12})$; and cummulative urinary excretion for 0-48 hours $(CLE_{0-48}.\;Mean\;AUC_{0-12},\;C_{max},\;and\;CUE_{0-48}$ values for formulations B and C were significantly different from formulation A (P<0.001), but not significantly diffeerent form each other. Basede on $AUL_{0-12}\;and\;CUE_{0-48}$ respectively, the relative availability of formulation B was 87.5% and 89.6% and the relative availability of formultation A was 43% and 35% when compared to formulation C(the standard).

• Archives of Pharmacal Research
• /
• v.29 no.1
• /
• pp.102-107
• /
• 2006

The aim of present study is to investigate the effect of naringin on the pharmacokinetics of verapamil and its major metabolite, norverapamil in rabbits. The pharmacokinetic parameters of verapamil and norverapamil were determined after administering verapamil (9 mg/kg) orally to rabbits in the pretreated with naringin (1.5, 7.5, and 15 mg/kg). Naringin pretreatment significantly altered the pharmacokinetic parameters of verapamil. Compared with the control group (given verapamil alone), the $K_a,\;C_{max}$ and AUC of verapamil were significantly (p<0.05 or p<0.01) increased in the pretreatment of naringin, However there were no significant change in $T_{max}\;and\;t_{1/2}$ of verapamil. Consequently, pretreatment of naringin significantly (p<0.05, p<0.01) increased the AB% of verapamil significantly in a dose dependent manner (p<0.05 or p<0.01 ), and elevated the RB% of verapamil by 1.26- to 1.69-fold. the MR of verapamil were significantly (p<0.05) increased in the pretreatment of naringin, implying that pretreatment of naringin may effectively inhibit the CYP3A4-mediated metabolism of verapamil. In conclusion, pretreatment of naringin enhanced the oral bioavailability of verapamil. Based on these results, the verapamil dosage should be adjusted when given with naringin or a naringin-containing dietary supplement.

• Archives of Pharmacal Research
• /
• v.26 no.10
• /
• pp.778-784
• /
• 2003

N'-(1-alkyl-2,3-dihydro-2-oxo-1H-3-indolyliden)-4-pyridinecarboxylic acid hydrazide derivatives, 3(a-g), were synthesized in a trial to overcome the resistance developed with the therapeutic uses of isoniazid (INH). The lipophilicity of the synthesized derivatives supersedes that of the INH as expressed by Clog p values. The synthesized compounds and INH were tested against bovin, human sensitive and human resist strains of Mycobacterium tuberculosis. Compounds 3a, 3d, 3f and 3g with 1-unsubstituted, 1-propyl, 1-propynyl and 1-benzyl groups respectively exhibited equipotent growth inhibitory activity (MIC 10 $\mu$mol) against the tested strains as compared with INH however the later has no activity against human resist strain. Pharmacokinetic study revealed that the rate and extent of absorption of the tested derivatives (3d and 3f) significantly higher than that of INH (p＜0.05). The relative bioavailabilities ($F_R%$) were 183.15 and 443.25 for 3f and 3d respectively as compared to INH. These results preliminary indicate the possible use of the prepared derivatives for treatment of tuberculosis infections in order to overcome the resistance developed with INH.

• Korean Journal of Clinical Pharmacy
• /
• v.19 no.1
• /
• pp.32-36
• /
• 2009

The aim of this study was to investigate the effect of simvastatin on the pharmacokinetics of nicardipine in rats. Pharmacokinetic parameters of nicardipine were determined after an oral administration of nicardipine (12 mg/kg) to rats coadministered with simvastatin (0.3 and 1.0 mg/kg). Compared with the control (given nicardipine alone), coadministration of simvastatin (1.0 mg/kg) significantly (p<0.05) increased the area under the plasma concentration (AUC) and peak plasma concentration ($C_{max}$) of nicardipine. The relative bioavailability (RB%) of nicardipine increased from 1.19- to 1.48-fold. However there were no significant changes in $t_{max}$, and $t_{1/2}$ of nicardipine. The enhanced oral bioavailability of nicardipine might be due to an inbition of cytochrom P450 3A mediated-metabolism of nicardipine in the intestine and in the liver by simvastatin. Based on these results, the concurrent use of simvastatin significantly enhanced the oral exposure of nicardipine in rats. The dosage regimen of nicardipine should be taken into consideration for potential drug interaction when combined with simvastatin in clinics.

• Mass Spectrometry Letters
• /
• v.5 no.3
• /
• pp.79-83
• /
• 2014

Three different dutasteride extraction methods were compared and a method based on liquid-liquid extraction (LLE) using methyl tert-butyl ether and methylene chloride was proved to be more effective than others for the extraction of dutasteride and finasteride, the internal standard (IS), from rat plasma. Additionally, a method composed of the LLE extraction, liquid chromatography, and multiple reaction monitoring (MRM) to target dutasteride and IS was validated by assessing specificity, linearity ($r^2$ = 0.9993, 5 - 400 ng/mL), sensitivity (the limit of detection: 4.03 ng/mL; the limit of quantitation: 12.10 ng/mL), accuracy (intra-day: 89.4 - 105.9%; inter-day: 84.9 - 100.9%), precision (intra-day: 0.8 - 6.9%; inter-day: 2.9 - 15.9%), and recovery (84.7 - 107.8%). Since the validated method was successfully applied to a pharmacokinetic study of dutasteride, it can be useful for the pharmacokinetic evaluation of newly developed dutasteride formulations.

• YAKHAK HOEJI
• /
• v.48 no.5
• /
• pp.278-284
• /
• 2004

In order to determine the bioavailability of c1onazepam, an anxiolytic drug, a simple, rapid and sensitive HPLC analysis was developed in healthy Korean volunteers. The analysis system was validated in specificity, accuracy, precision and linearity. The analysis condition we established was 2.58 min and 5 ng/$m\ell$ in retention time and limit of quantitation of c1onazepam, respectively, using reverse-phase C18 column connected to UV detector. Quantitation was performed at 235 nm wave length with p-hydroxybenzoic acid ethyl ester as internal standard. The method involved a simple extraction. In order to study blood level profiles as a function of time, eight volunteers were enrolled and orally took 6 mg clonazepam once. The blood samples were collected from 0 to 120 h after the drug administration. Mean AUC and Cmax value were 1028.17$\pm$568.165 (ng/$m\ell$$.$hr) and 41.25$\pm$10.82 (ng/$m\ell$), respectively. And mean Tmax and T$_{1}$2/ value were 1.08$\pm$0.42 (hr) and 30.78$\pm$3.26 (hr). From the results we determine the pharmacokinetic characteristics of clonazepam in Korean people using a newly developed and useful HPLC method.

• Analytical Science and Technology
• /
• v.35 no.2
• /
• pp.60-68
• /
• 2022

In this study, we developed and validated a sensitive analytical method to quantify baphicacanthin A in mouse plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The standard calibration curves for baphicacanthin A ranged from 0.5 to 200 ng/mL and were linear, with an r² of 0.985. The inter- and intra-day accuracy and precision and the stability fell within the acceptance criteria. Besides, we investigated the pharmacokinetics of baphicacanthin A following its intravenous (5 mg/kg) and oral administration (30 mg/kg). Intravenously injected baphicacanthin A showed biphasic elimination kinetics with high clearance and volume of distribution values. Furthermore, baphicacanthin A showed a rapid absorption but low aqueous solubility (182.51±0.20 mg/mL), resulting in low plasma concentrations and low oral bioavailability (2.49 %). Thus, we successfully documented the pharmacokinetic properties of baphicacanthin A using this newly developed sensitive LC-MS/MS quantification method, which could be used in future lead optimization and biopharmaceutic studies.

• YAKHAK HOEJI
• /
• v.50 no.6
• /
• pp.386-392
• /
• 2006

Pramlintide, a synthetic analogue of human hormone amylin, is the first of a new class of amylinomimetic compounds. Present study was undertaken to compile and analyze the clinical trials of pramlintide, and thereby to facilitate the design of the bridging study for the earlier introduction of the drug, which might be needed by diabetes patients in Korea. Sixty-two articles from Pubmed and MEDLINE search were used to analyze the trials of pramlintide along with prescribing information and New Drug Application packet obtained form the manufacturer. The efficacy of the new drug was attributed to three mechanisms: delay of gastric emptying time, inhibition of post-prandial glucagon secretion, and reduction of food intake by enhanced satiety. Clinical trials consistently identified the effectiveness of the drug for the treatment of type 1and type 2 diabetes who have failed to achieve glycemic control despite optimal therapy with insulin. However, the six pivotal Phase III clinical trials were peformed with mostly caucasian and some black and hispanic people. None of the trials documented the proportion of either Asian or Korean participants. Since Korean diabetes patients show different epidemiology and characteristics in their disease state, it appears that the bridging study of pramlintide should be designed in the level of full scale Phase III clinical trial along with pharmacokinetic and pbarmacodynamic studies.