• Biomolecules & Therapeutics
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• v.19 no.2
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• pp.248-254
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• 2011

Biotransformation of pharmacologically inactive lactone prodrug simvastatin (SV) into pharmacologically active simvastatin ${\beta}$-hydroxy acid (SVA) exhibits inter-species differences due to variations in amount and activity of esterase enzymes. In this study, we investigated the pharmacokinetics (PK) of SV and its metabolite SVA following oral doses of SV from controlled-release (CR) tablets and immediate-release (IR) tablets in rodent and canine animal models that features different esterase activity. In rat PK study, no SV was detected in plasma for both formulations due to rapid hydrolysis of SV into SVA by plasma esterase. Besides, no significant differences in PK parameters of SV or SVA were observed between both species. In dog PK study, the relative oral bioavailability of CR tablets in terms of SV was 72.3% compared to IR tablets. Regarding formulation differences in dogs, CR tablets exhibited significantly lower $C_{max}$ (p<0.05), and higher $T_{max}$ (p<0.01) and MRT (p<0.01) for both SV and SVA compared to IR tablets. Accordingly, CR tablets of SV with prolonged drug release profiles in both species might be a potential candidate for a more effective delivery of SV with reduced side effects. Besides, similar PK parameters of SV and SVA in both species despite variation in enzyme activities suggested involvement of equally potent biotransformation pathways in these animal species.

• Korean Journal of Veterinary Research
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• v.43 no.2
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• pp.203-210
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• 2003

The purpose of this study is to investigate the pharmacokinetics and tissue distribution of recombinant bovine somatotropin (rBST) after subcutaneous adminstration of $^{125}I-rBST$ in male and female rats. A solid state conjugation (Iodo-bead$^{(R)}$) method was confirmed useful for producing $^{125}I-rBST$ because the administration of the conjugated form enabled enough to determine time- concentration relationships of rBST in rats. Subcuatenous administrations showed sex differences that female ($t_{1/2,kc}$, 2.87 h) revealed rapid elimination as compared to male ($t_{1/2,ke}$, 4.81 h), with the absorption ($t_{1/2,ka}$ in male being 0.3 h and that in female 0.75 h) in the reverse order. For subcutaneous administration of rBST in male rats, the liver was the highest in amount, followed by kidney, testes, muscle, and stomach, at the slaughtering tame of 1, 6, 12 and 24 h. But the testes was the highest at the 48 h slaughtered animals, followed by liver, kidney, stomach, and muscle. In slaughtered females at 1, 6, and 12 h after the administration of rBST, the liver was the highest, followed by ovary, kidney, small intestine, and stomach. At 24 and 48 h slaughtered female rats, the ovary was the highest, the liver the second, and the kidney the third.

• Journal of Life Science
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• v.26 no.1
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• pp.123-128
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• 2016

The object of this study was to obtain accurate information about the co-administration effects of cardiotonic pills on the pharmacokinetics of cilostazol were observed as a process of the comprehensive and integrative medicine. Cilostazol is a synthetic anti-platelet and vasodilator agent developed for the treatment of intermittent claudication resulting from peripheral arterial disease. By increasing intracellular cyclic adenosine monophosphate (cAMP), cilostazol induces the activation of protein kinase A, which activates endothelial nitric oxide synthase. In order to evaluate the effect of a single or repeated cardiotonic pill dose on the pharmacokinetics of cilostazol, a single dose of pure_distilled water or a colloidal suspension of distilled water and cardiotonic pills were administered to the control and test groups, respectively. After 30 min, both groups were administered cilostazol. Plasma was collected 30min before administration, and 0.25, 0.5, 0.45, 1, 2, 4, 6, 8, and 24h after the end of cilostazol treatment. We then evaluated the pharmacokinetic changes observed with cilostazol between the control and test groups. No statistically significant differences were observed. These findings demonstrated that a single dose of cardiotonic pills did not affect the pharmacokinetics of cilostazol. The results obtained in this study suggest that co-administration of cardiotonic pills and cilostazol may not affect the bioavailability of cilostazol as a potential drug interaction.

• Korean Journal of Clinical Pharmacy
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• v.9 no.2
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• pp.88-91
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• 1999

The purpose of this study was to compare the pkarmacokinetic parameters of vancomycin using a 2-compartment model in 8 Korean healthy volunteers and 8 lymphoma patients. Vancomycin (1.0 g) was administered by IV infusion over 60 minutes. The $\beta-phase$ rate constant $(\beta)$, apparent volume of distribution at steady srate $(V_{ss})$, total body clearance (CL) and area under the plasma level-time curve (AUC) of vancomycin in healthy volunteers were $0.15\pm0.02\;hr^{-1},\;33.8\pm4.12\;L/kg,\;5.36\pm0.61\;L/hr\;and\;185.8\pm20.5\;{\mu}g/ml{\cdot}hr$, respectively. The corresponding values in lymphoma patients ere $0.09\pm0.02\;hr^{-1},\;38.2\pm5.11\;L/kg,\;4.58\pm0.52\;L/hr\;and\;218.3\pm22.9\;{\mu}g/ml{\cdot}hr$. There were significant differences (p<0.05) in ${\beta}$ and CL between healthy volunteers and lymphoma patients.

• Archives of Pharmacal Research
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• v.19 no.4
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• pp.297-301
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• 1996

Plasma profile of niflumic acid following oral administration of talniflumate tablets (Somalgen) was compared to that of niflumic acid tablets in man. Plasma niflumic acid was assayed by HPLC method. Plasma niflumic acid profile from the tainiflumate tablets was similar to that from the niflumic acid tablets resulting in no differences in $AUC, C_max, t_max$ and MRT. It demonstrates that talniflumate is a prodrug of niflumic acid, and undergoes extensive first-pass biotransformation to niflumic acid. However, plasma niflumic acid concentration at 30 min after tainiflumate dosing was significantly (p<0.05) higher than that of niflumic acid dosing. The more potent analgesic activity of talniflumate than niflumic acid might be related to this higher plasma drug concentration at the earlier phase. Considering that tainiflumate is less irritant to gastrointestinal mucosa than niflumic acid, talniflumate seems to be advantageous over niflumic acid in terms of activity and side effects.

• Korean Journal of Clinical Pharmacy
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• v.5 no.2
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• pp.1-12
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• 1995

The purpose of this investigation was to determine pharmacokinetic parameters of gentamicin using linear least square regression(LLSR) and Bayesian analysis in Korean normal volunteers and appendicitis patients. Nonparametric expected maximum(NPEM) algorithm for population pharmacokinetic parameters was used. Gentamicin was administered every 8 hours for 3 days by infusion over 30 minutes. The volume of distribution(V) and elimination rate constant(K) of gentamicin were $0.215\pm0.0562,\;0.226\pm0.0325L/kg\;and\;0.339\pm0.0443,\;0.357\pm0.0243hr^{-1}$ for normal volunteers and appendicitis patients using LLSR analysis. Population pharmacokinetic parameters, VS and KS were $0.228\pm0.0614L/kg\;and\;0.00356\pm0.00041(hr{\cdot}mL/min/1.73m^2)^{-1}$ for appendicitis patients using NPEM algorithm. The V and K were $0.232\pm0.0568L/kg\;and\;0.337\pm0.0385hr^{-1}$ for appendicitis patients using Bayesian analysis. There were no differences in gentamicin pharmacokinetics between LLSR and Bayesian analysis.

• YAKHAK HOEJI
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• v.45 no.2
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• pp.153-160
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• 2001

This research developed an intravenous (IV) vancomycin dosing nomogram based on the clinical pharmacokinetic data of Korean adult patients. Total 99 pairs of steady-state peak and trough serum concentrations of vancomycin were obtained from 73 adult patients in a tertiary general hospital. Serum vancomycin concentrations were determined to assess the appropriateness of initial vancomycin dosing. Only 47.2% of the cases were within therapeutic range. To characterize the clinical pharmacokinetics (PK) of vancomycin, PK parameters including elimination rate constant ( $K_{e}$) half-life( $T_{1}$2/), clearance (C $l_{van}$), volume of distribution ( $V_{d}$) were calculated by using one-compartment, first order pharmacokinetic equations. PK parameters were evaluated based on the differences of patients'renal function and age. Regression analysis showed a significant correlation between C $l_{van}$ and $C_{cr}$ (C $l_{van}$ = -1.89+0.914 $C_{cr}$ , r=0.763) and between $K_{e}$ and $C_{cr}$ , ( $K_{e}$=-0.0037+0.00139 $C_{cr}$ =0.724). The relationship between $K_{e}$ and $C_{cr}$ , and the mean $V_{d}$ were utilized for developing the nomogram to individualize the initial dosing regimen of vancomycin for the patients with various degrees of renal functions. The nomogram may be used as an efficient tool to determine safe and effective doses of vancomycin for the Korean adult patients.nts.nts.nts.s.nts.

• Korean Journal of Clinical Pharmacy
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• v.8 no.2
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• pp.107-112
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• 1998

Lovastatin is a lipid lowering agent for the treatment of hypercholesterolemia and belongs to a new class of pharmacologic compounds called the 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors. By competitively inhibiting HMG CoA reductase, lovastatin disrupts the biosynthesis of cholesterol in hepatic and peripheral cells and increases the synthesis of high-density-lipoprotein HDL) receptors. Following oral administration, the lactone ring of lovastatin is hydrolysed to the active inhibitor of HMG CoA reductase, lovastatin acid. Lovastatin is known to have poor oral absorption and wide individual variation. In this study, bioequivalence test of two lovastatin formulations, the test drug ($Lovaload^{TM}$, Chong Kun Dang Pharmaceutical Co.) and the reference drug ($Mevacor^{TM}$, Chung Wae Pharmaceutical Co.) were conducted according to the guidelines of Korea Food and Drug Administration (KFDA). A total of 18 healthy male volunteers, $31.90\pm3.60$ years old and $72.17\;7.88$ kg of body weight in average, were evaluated in a randomized crossover manner with a 2-week washout period. Concentrations of lovastatin acid in plasma were measured upto 12 hours following a single oral administration of eight tablets (20 mg of lovastatin per tablet) by high-performance liquid chromatography with UV detection at 238 nm. The area under the concentration-vs-time curve from 0 to 12 hours $(AUC_{0-12h})$ was calculated by the trapezoidal summation method. The statistical analysis showed that there are no significant differences in $AUC_{0-12h),\;C_{max}\;and\;T_{max}$ between the two formulations ($6.72\%,\;1.52\%,\;and\;0.88\$, respectively). The least significant differences between the formulations at $\alpha$=0.05 were less than $20\%\;(11.65\%,\;19.73\%,\;and\;14.81\%\;for\;AUC_{0-12h},\;C_{max}\;and\;T_{max}$, respectively). The $90\%$ confidence intervals for these parameters were also within $\pm20\%\;(-1.50{\leq}{\delta}{\leq}15.00$, $-12.50{\leq}{\delta}{\leq}15.50,\;and\;-9.64{\leq}{\delta]{\leq}11.40{\leq}\;for\;\;AUC_{0-12h}$ ,$C_{max}\;and\;T_{max}$, respectively). In conclusion, the new generic product $Lovaload^{TM}$ was proven to be bioequivalent with the reference drug.

• Food Engineering Progress
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• v.21 no.3
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• pp.273-279
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• 2017

Curcumin have various health-beneficial properties in numerous studies. However, its bioavailability is low due to its limited intestinal uptake and rapid metabolism. This study aimed to evaluate the pharmacokinetics of newly developed sub-micron particle curcumin with increased water dispersibility (Theracurmin(R) CR-033P). Plasma curcumin levels were measured at 0, 1, 2, 4, 8 h after Theracurmin(R) CR-033P intake using high-performance liquid chromatography. For analyzing pharmacokinetics of Theracurmin(R) CR-033P, eighteen healthy subjects were recruited and received Theracurmin(R) CR-033P at a single oral dose containing curcumin 30 mg. $C_{max}$ was 28.14 ng/ml, and the area under the curve for 8 h was estimated to be 104.36 ng/ml. Based on the area under the plasma concentration (AUC), the bioavailability of sub-micron particle curcumin was higher 22-, 35-, 28-fold than native curcumin in men, women, and all subjects, respectively. For comparing by formulation, seven healthy subjects were recruited and received two type of treatment: (1) existing dosage form 300 mg (contained curcumin 30 mg) ${\times}$ 3 capsule, (2) high dosage form 300 mg (contained curcumin 90 mg) ${\times}$ 1 capsule + placebo 300 mg ${\times}$ 2 capsule. In the cross-over study, there was no significant differences in $C_{max}$ and AUC of plasma curcumin. In conclusion, submicron particle curcumin with increased water dispersibility significantly improved its oral bioavailability and women absorbed curcumin more effectively than men. Different formulation of Theracurmin(R) CR-033P has shown equivalent to the reference in terms of pharmacokinetics.

• Journal of Ginseng Research
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• v.23 no.3 s.55
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• pp.172-175
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• 1999

The effect of Korean red ginseng extract on the pharmacokinetics of ethanol was examined in 14 male rats and 10 healthy male volunteers. Aqueous red ginseng extract (200 mg/kg), or an equivalent volume of water was administered orally to the rats and followed immediately by treatment with $50\%$ (v/v) ethanol orally (3.2 g/kg). The area under the curve (AVC) and elimination rate constant (Ke) of ethanol were $29.2{\pm}6.2\;g{\cdot}min{\cdot}dl^{-},\;0.51{\pm}0.06\;mg{\cdot}dl^{-}{\cdot}min.^{-}$ in ginseng-treated group and $28.0{\pm}5.6\;g{\cdot}min.{\cdot}dl^{-},0.5{\pm}0.1\;mg{\cdot}dl^{-}{\cdot}min.^{-}$ in control group. These differences were not significant. The volunteers were given orally with 3g of aqueous ginseng, or an equivalent volume of water, followed immediately by Korean alcoholic beverage, Soju (2.4 ml/kg). The AUC and Ke of ethanol for volunteers were $10.6{\pm}2.0\;g{\cdot}min.{\cdot}dl^{-}$ and $0.21{\pm}0.05\;mg{\cdot}dl^{-}{\cdot}min.^{-}$ in ginseng-treated group and $11.0{\pm}2.2\;g{\cdot}min.{\cdot}dl^{-}$ and $0.22{\pm}0.04\;mg{\cdot}dl^{-}{\cdot}min.^{-}$ in control group. These differences were not also significant. These results suggest that an application of red ginseng extract does not have any clinically significant effect on the pharmacokinetics of ethanol.