Min-Koo Choi

Dankook University, Eidō, North Chungcheong, South Korea

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Publications (41)99.72 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The objective of this study was to investigate the contributions of a sodium-dependent concentrative nucleoside transporter (CNT) 1 and an equilibrative nucleoside transporter (ENT) 1 to ribavirin uptake in human hepatocytes. The initial studies in oocytes expressing CNT1 and ENT1 showed increases in ribavirin uptake, indicating that ribavirin was a substrate for both CNT1 and ENT1. The CNT1- and ENT1-mediated ribavirin uptake showed concentration dependency with the following kinetics parameters: Km 26.3 μM and Vmax 426.2 fmol/min/oocyte for CNT1; Km 70.5 μM and Vmax 134.3 fmol/min/oocyte for ENT1. Ribavirin uptake clearance in six human hepatocytes ranged from 21.3 to 300.7 μL/min. Estimation of the contributions of CNT1 and ENT1 to the hepatic uptake of ribavirin by using a relative activity factor method indicated that the relative contribution of ENT1 to the ribavirin uptake was 82.8 ± 3.9 %. Real-time polymerase chain reaction analysis of CNT1 and ENT1 expressions in the hepatocytes showed that ENT1 mRNA expression was closely correlated with ribavirin uptake (R = 0.95, P = 0.003) while CNT1 was not. The findings indicated that ENT1 was the major transporter controlling the hepatic uptake of ribavirin.
    Archives of Pharmacal Research 07/2014; · 1.54 Impact Factor
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    ABSTRACT: The purpose of this study was to develop a biobetter version of recombinant human interferon-β 1a (rhIFN-β 1a) to improve its biophysical properties, such as aggregation, production and stability, and pharmacokinetic properties without jeopardizing its activity. To achieve this, we introduced additional glycosylation into rhIFN-β 1a via site-directed mutagenesis. Glycoengineering of rhIFN-β 1a resulted in a new molecular entity, termed R27T, which was defined as a rhIFN-β mutein with two N-glycosylation sites at 80th (original site) and at an additional 25th amino acid due to a mutation of Thr for Arg at position 27th of rhIFN-β 1a. Glycoengineering had no effect on rhIFN-β ligand-receptor binding, as no loss of specific activity was observed. R27T showed improved stability and had a reduced propensity for aggregation and an increased half-life. Therefore, hyperglycosylated rhIFN-β could be a biobetter version of rhIFN-β 1a with a potential for use as a drug against multiple sclerosis.
    PLoS ONE 01/2014; 9(5):e96967. · 3.53 Impact Factor
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    ABSTRACT: We investigated the in vitro metabolic stability and transport mechanism of TM-25659, a novel TAZ modulator, in human hepatocytes and human liver microsomes (HLMs) based on the preferred hepatobiliary elimination in rats. In addition, we also evaluated in vitro transport mechanism and transporter-mediated drug-drug interactions using oocytes and MDCKII cells overexpressing clinically important drug transporters. After 1 h incubation in HLMs, 92.9 ± 9.5% and 95.5 ± 11.6% of initial TM-25659 remained in the presence of NADPH and UDPGA, respectively. The hepatic uptake of TM-25659 readily accumulated in human hepatocytes at 37 °C (i.e. 6.7-fold greater than that at 4 °C), in which drug transporters such as OATP1B1 and OATP1B3 were involved. TM-25659 had a significantly greater basal to apical transport rate (5.9-fold) than apical to basal transport rate in the Caco-2 cell monolayer, suggesting the involvement of an efflux transport system. Further studies using inhibitors of efflux transporters and overexpressing cells revealed that MRP2 was involved in the transport of TM-25659. These results, taken together, suggested that TM-25659 can be actively influxed into hepatocytes and undergo biliary excretion without substantial metabolism. Additionally, TM-25659 inhibited the transport activities of OATP1B1 and OATP1B3 with IC50 values of 36.3 and 25.9 μM, respectively. TM-25659 (100 μM) increased the accumulation of probe substrate by 160% and 213%, respectively, through the inhibiton of efflux function of P-gp and MRP2. In conclusion, OATP1B1, OATP1B3, P-gp, and MRP2 might be major transporters responsible for the pharmacokinetics and drug-drug interaction of TM-25659, although their contribution to in vivo pharmacokinetics need to be further investigated. This article is protected by copyright. All rights reserved.
    Biopharmaceutics & Drug Disposition 11/2013; · 2.09 Impact Factor
  • Min-Koo Choi, Im-Sook Song
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    ABSTRACT: We aimed to characterize the efflux transport properties of vardenafil and sildenafil, and to compare the kinetics of these compounds via efflux transporters such as P-gp, BCRP and MRP2. We measured the basal-to-apical and apical-to-basal transport of vardenafil and sildenafil within the concentration range of 1-100 µm using MDCKII cells overexpressing P-gp, BCRP and MRP2, and Caco-2 cells. Vardenafil had a much greater basal-to-apical than apical-to-basal transport rate in MDCKII cells overexpressing P-gp, BCRP and MRP2. Sildenafil showed P-gp- and BCRP-mediated efflux transport, but did not seem to be pumped out via MRP2 transporters. Consequently, the absorptive transport of vardenafil and sildenafil in Caco-2 cells increased linearly over the concentration range of 1-100 µm, whereas the secretory transport of these drugs was saturable and inhibited by the presence of specific inhibitors of P-gp and BCRP. MK571, a representative MRP2 inhibitor, inhibited the basal-to-apical transport of vardenafil, but not of sildenafil. The involvement of P-gp, BCRP and MRP2 for vardenafil and the involvement of P-gp and BCRP for sildenafil in the secretory transport with linear absorptive transport may contribute to the limited intestinal absorption of these drugs.
    The Journal of pharmacy and pharmacology. 08/2012; 64(8):1074-83.
  • Min-Koo Choi
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    ABSTRACT: The concentrative nucleoside transporter CNT1 and equilibrated nucleoside transporter ENT1 mediate the cellular uptake of naturally occurring pyrimidine and purine nucleosides and many structurally diverse anticancer and antiviral nucleoside analogs, thereby regulating drug responses or toxicity at the target site. The objectives of this study were to analyze interindividual variations in the cellular accumulation of gemcitabine and to examine the correlation between the uptake of gemcitabine and expression levels of CNT1 and ENT1 transporters. Gemcitabine was a substrate for both CNT1 and ENT1 with higher affinity to CNT1 than to ENT1. The difference in gemcitabine uptake was 4.8-fold in peripheral blood mononuclear cells (PBMCs) from 10 subjects. Among these, the CNT1- and ENT1-mediated uptake of gemcitabine was 14.3- and 16.5-folds, respectively. CNT1-mediated gemcitabine uptake showed a higher correlation with the CNT1 expression level than did ENT1-mediated uptake with ENT1 expression level. In conclusion, CNT1 seemed to be a major contributing factor to gemcitabine uptake in PBMCs and showed 14.3-fold inter-individual variations. However, ENT1-mediated uptake of gemcitabine might compensate for the total uptake of gemcitabine; therefore, the variation in the apparent accumulation of gemcitabine was smaller than that of the individual transporters.
    Archives of Pharmacal Research 05/2012; 35(5):921-7. · 1.54 Impact Factor
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    ABSTRACT: We recently reported that Val-SN-38, a novel valine ester prodrug of SN-38, had greatly improved the intracellular accumulation of SN-38 in MCF-7 cell line, probably through enhanced uptake via amino acid transporters. In the present study, the efficacy of Val-SN-38 was further investigated both in vitro and in vivo. It was found that the in vitro cytotoxic effect of Val-SN-38 was similar to that of SN-38. Moreover, Val-SN-38 exhibited an equal potency to that of SN-38 in survival experiments in vivo. Because these results seemed to be contrary to the previous finding, further investigation was performed to find out the underlying cause of the contradiction. As only the lactone form is known to have cytotoxic activity, the proportion of lactone in Val-SN-38 and SN-38 was determined, but no differences were found. However, it turned out that Val-SN-38 had poor stability compared with SN-38, which resulted in a decrease in beneficial efficacy for Val-SN-38. Overall, the present study showed that a valine-added prodrug approach could be advantageous provided that the stability of the compound can be ensured. We believe this is a noteworthy study that unravels the discrepancy between intracellular accumulation and efficacy of valine-added prodrug.
    Biomolecules and Therapeutics 05/2012; 20(3):326-331. · 0.79 Impact Factor
  • Min-Koo Choi, Im-Sook Song
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    ABSTRACT: The study sought to investigate the effect of genetic variants of OCT1 (OCT1-P283L and -P341L) and OCT2 (OCT2-T199I, -T201M and -A270S), which were identified in a Korean population, on the transport of lamivudine in vitro and to compare the substrate dependent effects of OCT1 and OCT2 variants with 1-methyl-4-phenylpyridinium (MPP+), tetraethyl ammonium (TEA), metformin and lamivudine as substrates for these transporters. When the transport kinetics of lamivudine uptake in oocytes overexpressing OCT1 and OCT2 wild-type (WT) and variant proteins were measured, lamivudine uptake mediated by OCT1-WT was saturable, and uptake was decreased in oocytes expressing OCT1-P283L and -P341L variants compared with that in OCT1-WT. The Clint of lamivudine in oocytes expressing OCT1-P283L was decreased by 85.1% compared with OCT1-WT, whereas it was decreased by 48.7% in oocytes expressing OCT1-P341L. The Clint of lamivudine in oocytes expressing OCT2-T199I, -T201M and -A270S was decreased by 86.2%, 88.9% and 73.6%, respectively, compared with OCT2-WT. When comparing various substrates such as MPP+, TEA, metformin and lamivudine, the effects of the OCT1 genetic polymorphisms on their uptake were not identical. However, contrary to the case of OCT1, the uptake of MPP+, TEA, metformin and lamivudine in oocytes expressing OCT2-T199I, -T201M and -A270S variants was decreased significantly compared with that in oocytes expressing OCT2-WT. In conclusion, the effect of genetic variations of OCT1 and OCT2 on the uptake of MPP+, TEA, metformin and lamivudine was substrate-dependent.
    Biopharmaceutics & Drug Disposition 03/2012; 33(3):170-8. · 2.09 Impact Factor
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    ABSTRACT: The effect of fatty acids on the skin permeation of donepezil base (DPB) and its hydrochloride salt (DPH) were studied in vitro using hairless mouse and human cadaver skin. DPB and DPH were solubilized in propylene glycol (PG) containing 1% (w/v) fatty acid, after which the in vitro permeation through hairless mouse skin and human cadaver skin were evaluated using Keshary-Chien diffusion cells. The optimized formulation obtained from the in vitro study was then tested in rats for an in vivo pharmacokinetic study. The relative in vitro skin permeation rate of donepezil (DP) through the hairless mouse skin showed a parabolic relationship with increased carbon length of the fatty acid enhancers. Among the fatty acids tested, oleic acid for DPB and palmitoleic acid for DPH showed the highest enhancing effect, respectively. Both the permeation rates of DPB and DPH evaluated in human cadaver skin were in good correlation with those in hairless mouse skin, regardless of the presence of fatty acids. This suggests that the mouse skin model serves as a useful in vitro system that satisfactorily represents the characteristics of the human skin. Moreover, based on the in vitro results, the optimal formulation that could maintain the human plasma concentration of 50 ng/mL was determined to be 10mg DP with 1% (w/v) enhancer. When the DP transdermal formulations were applied to the abdominal skin of rats (2.14 cm(2)), the C(ss) was maintained for 48 h, among which the highest value of 52.21 ± 2.09 ng/mL was achieved with the DPB formulation using oleic acid. These results showed that fatty acids could enhance the transdermal delivery of DP and suggested the feasibility of developing a novel transdermal delivery system for clinical use.
    International Journal of Pharmaceutics 01/2012; 422(1-2):83-90. · 3.99 Impact Factor
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    ABSTRACT: It is well known that the CYP2C19 genetic polymorphism influences the pharmacokinetics and pharmacodynamics of proton pump inhibitors (PPIs), but no report has addressed the effects on ilaprazole, a newly developed PPI. To investigate the effects of the CYP2C19 genetic polymorphism on the disposition and pharmacodynamics of ilaprazole, multiple doses of once-daily 10 mg ilaprazole were repeatedly administered for 7 days to 27 healthy Korean participants, comprising 9 homozygous CYP2C19 extensive metabolizers (homo EMs), 10 heterozygous EMs (hetero EMs), and 8 homozygous poor metabolizers (PMs). The plasma concentration and pharmacodynamic response were measured in the last dose interval. Each genotype group was matched for gender and thus was composed of 4 male and 4 female participants when the analysis was conducted. The pharmacokinetic parameters estimated from the plasma concentrations of ilaprazole and its metabolite ilaprazole sulfone, the serum gastrin level, and the 24-hour intragastric pH were compared among the CYP2C19 genotype groups. No statistically significant differences in the maximum plasma concentration at steady state(C(ss,max)) and the area under the concentration-time curve from zero to 24 hours (AUC(τ)) of ilaprazole and ilaprazole sulfone were observed among the homo EM, hetero EM, and PM CYP2C19 genotypes. In addition, the mean 24-hour intragastric pH, the percentage of time at pH >4, and the AUC(τ) of serum gastrin showed no significant differences among the CYP2C19 genotype groups. The data suggests that the pharmacokinetics and pharmacodynamics of ilaprazole are not significantly influenced by the CYP2C19 genetic polymorphism in healthy participants.
    The Journal of Clinical Pharmacology 05/2011; 52(7):976-84. · 2.84 Impact Factor
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    ABSTRACT: Ketoconazole and rifampin are the most widely used compounds examined in recent drug-drug interaction (DDI) studies, and they have multiple roles in modulating drug metabolizing enzymes and transporters. To determine the underlying mechanisms of DDI, this study was performed to investigate the inhibitory effects of ketoconazole and rifampin on the functions of OAT1 and OATP1B1, and to evaluate the potential of ketoconazole and rifampin for DDI with substrate drugs for these transporters in a clinical setting. Ketoconazole inhibited OATP1B1-mediated transport activity, while rifampin inhibited OAT1 and OATP1B1. Inhibition by rifampin and ketoconazole of the uptake of olmesartan, a substrate for OAT1 and OATP1B1, was evaluated in oocytes overexpressing these transporters. The K(i) values for rifampin on OAT1 and OATP1B1-mediated olmesartan uptake were 62.2 and 4.42 µM, respectively, and the K(i) value for ketoconazole on OATP1B1-mediated olmesartan uptake was 66.1 µM. As measured plasma concentrations of rifampin and ketoconazole were 7.29 and 6.4-13.3 µM, respectively, the likelihood of an OATP1B1-mediated drug-drug interaction between rifampin and olmesartan is thought to be possible, whereas OAT1 or OATP1B1-mediated DDI between rifampin or ketoconazole and olmesartan appears unlikely in the clinical setting.
    Biopharmaceutics & Drug Disposition 04/2011; 32(3):175-84. · 2.09 Impact Factor
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    ABSTRACT: 1. The pharmacokinetics of metoprolol after intravenous (IV) (0.5, 1, and 2 mg/kg) and oral (1, 2, and 5 mg/kg) administration, and the intestinal and hepatic first-pass extraction of metoprolol after IV, intraportal, and intraduodenal (1 and 2 mg/kg) administration were comprehensively assessed in rats. 2. Metoprolol exhibited dose-independent pharmacokinetics after IV administration, and dose-dependent pharmacokinetics after oral administration probably due to the saturable first-pass extraction of metoprolol. At doses where metoprolol exhibited dose-independent pharmacokinetics (1 and 2 mg/kg), complete absorption (>99.2%) and low F (<0.245) after oral administration were observed. The intestinal and hepatic first-pass extraction ratio (E(G) and E(H), respectively) of metoprolol were approximately 0.45 and 0.60, respectively (equivalent to approximately 45% and 30% of orally administered dose, respectively), suggesting considerable contribution of intestinal first-pass extraction to the low F of metoprolol in rats. 3. The E(G) in rats was predicted from in vitro clearance and/or permeability data utilizing the Q(Gut) model and well-stirred model (0.347 and 0.626, respectively). The predicted E(G) values were in good agreement with the observed in vivo E(G) (0.492-0.443), suggesting the utility of the prediction of in vivo intestinal first-pass extraction from the in vitro clearance using intestinal microsomes.
    Xenobiotica 03/2011; 41(3):243-51. · 1.98 Impact Factor
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    ABSTRACT: P-glycoprotein (P-gp) is an efflux transporter encoded by the multidrug resistance gene (MDR1), which is also known as the human ABCB1 gene (ATP-binding cassette, subfamily-B). The objectives of this study were to investigate the expression of P-gp in passaged primary human nasal epithelial (HNE) cell monolayer, cultured by the air-liquid interface (ALI) method, and to evaluate its feasibility as an in-vitro model for cellular uptake and transport studies of P-gp substrates. Reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to verify the expression of the MDR1 gene. Transport and cellular uptake studies with P-gp substrate (rhodamine123) and P-gp inhibitors (verapamil and cyclosporin A) were conducted to assess the functional activity of P-gp in HNE cell monolayers cultured by the ALI method. MDR1 gene expression in primary HNE cell monolayers cultured by ALI method was confirmed by RT-PCR. The apparent permeability coefficient (P(app) ) of the P-gp substrate (rhodamine123) in the basolateral to apical (B to A) direction was 6.9 times higher than that in the apical to basolateral (A to B) direction. B to A transport was saturated at high rhodamine123 concentration, and the treatment of P-gp inhibitors increased cellular uptake of rhodamine123 in a time- and concentration-dependent manner. These results support the MDR1 gene expression and the functional activity of P-gp in primary HNE cell monolayers cultured by the ALI method.
    The Journal of pharmacy and pharmacology. 03/2011; 63(3):385-91.
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    ABSTRACT: To assess potential interactions between sitagliptin and metformin, we sought to characterize the in vitro inhibitory potency of sitagliptin on the uptake of MPP(+) and metformin, representative substrates for OCTs, and to evaluate the pharmacological pathways that may be affected by the combination of metformin and sitagliptin. Among the OATs and OCTs screened, OAT3-mediated salicylate uptake and OCT1- and OCT2-mediated MPP(+) uptake were inhibited by sitagliptin. The K(i) values of sitagliptin for OCT1- and OCT2-mediated metformin uptake were 34.9 and 40.8 μM, respectively. As OCT1 is the gate protein for metformin action in the liver, we investigated whether sitagliptin-mediated OCT1 inhibition affected metformin-induced activation of AMPK signalling. Treatment with sitagliptin in MDCK-OCT1 and HepG2 cells resulted in a reduced level of phosphorylated AMPK, with K(i) values of 38.8 and 43.3 μM, respectively. These results suggest that the inhibitory potential of sitagliptin on OCT1 may attenuate the first step of metformin action, that is, the phosphorylation of AMPK. Nevertheless, the likelihood of a drug-drug interaction between sitagliptin and metformin is believed to be remote in usual clinical setting.
    Xenobiotica 12/2010; 40(12):817-25. · 1.98 Impact Factor
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    ABSTRACT: The purpose of this study was to investigate the effect of genetic variations in organic anion-transporting polypeptide 1B1 (OATP1B1) and Na(+)/taurocholate co-transporting polypeptide (NTCP) on the uptake of various statins having different affinities for these transporters. The functional activities and simultaneous expression of NTCP and OATP1B1 were confirmed by the uptake of taurocholate and estrone-3-sulphate as representative substrates for NTCP and OATP1B1, respectively, and by an immunofluorescence analysis. The substrate specificities of NTCP and OATP1B1 for statins and the effects of genetic variations on the uptake of rosuvastatin, pitavastatin, and atorvastatin were measured. Based on the K(m) values and intrinsic clearances of the three statins, pitavastatin was taken up more efficiently than rosuvastatin and atorvastatin by OATP1B1. Consequently, the cellular accumulation of pitavastatin was modulated according to the genetic variation of OATP1B1 (OATP1B1*15), rather than NTCP*2. In contrast, NTCP*2 displayed greater transport of atorvastatin and rosuvastatin, compared with NTCP wild type. Thus, the measurements of decreased rosuvastatin and atorvastatin transport by OATP1B1*15 were confounded by the presence of NTCP and its genetic variant, NTCP*2. In conclusion, the functional consequences of genetic variants of NTCP and OATP1B1 may be different for various statins, depending on the substrate specificity of the OATP1B1 and NTCP transporters.
    Xenobiotica 10/2010; 41(1):24-34. · 1.98 Impact Factor
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    ABSTRACT: We intended to elucidate the mechanism of the molecular weight (Mw) threshold (i.e., 200 +/- 50) for appreciable hepatobiliary excretion of quaternary ammonium compounds (QACs) in rats. We measured the effect of ion-pair complexation of QACs with taurodeoxycholate (TDC), an endogenous anionic bile salt, on the apparent partition coefficients (APC) of QACs between n-octanol and phosphate buffer, and the inhibition of organic cation transporter1 (OCT1)- and P-glycoprotein (P-gp)-mediated transport of representative substrates. By measuring the APC, we demonstrated that there is a Mw threshold of 200 +/- 50 in the ion-pair complexation of QACs with an endogenous bile salt, TDC. We also demonstrated, by measuring the inhibition of relevant transports, that a Mw threshold of 200 +/- 50 exists for the binding of QACs to canalicular P-gp, but not for sinusoidal OCT1. The Mw threshold values for ion-pair formation and P-gp binding were identical and consistent with the reported Mw threshold value for appreciable biliary excretion of QACs in rats. Mw-dependent binding of QACs to canalicular P-gp contributes in part to the mechanism of the Mw threshold of 200 +/- 50. The formation of lipophilic ion-pair complexes with bile salts, followed by stronger binding to canalicular P-gp, appears to accelerate biliary excretion of QACs with a high Mw.
    Pharmaceutical Research 03/2010; 27(5):823-31. · 4.74 Impact Factor
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    ABSTRACT: Hyaluronic acid (HA)-based microspheres containing PEG 6000 and/or sodium taurocholate (NaTC) were prepared by the spray-drying method for nasal delivery of fexofenadine hydrochloride (HCl). Their physicochemical properties including particle size and drug contents were determined, while their morphology examined by a scanning electron microscope (SEM). The effects of the solubilizer (PEG 6000) and the permeation enhancer (NaTC) on the in vitro release characteristics of fexofenadine x HCl were observed. Moreover, the in vitro permeation of fexofenadine x HCl was determined using the human nasal cell (HNE) monolayers cultured on Transwell inserts. After nasal administration, fexofenadine x HCl in rabbit plasma was determined by the LC-MS/MS system. Fexofenadine x HCl-loaded microspheres were of spherical shape with 20-30 microm mean diameter. The loading efficiency was about 95%. In vitro release of fexofenadine x HCl from the microspheres was significantly increased with the addition of PEG 6000. Although NaTC did not alter the in vitro release of drug from the microspheres, its addition further increased the in vitro permeation of fexofenadine x HCl across the HNE cell monolayers. Moreover, the bioavailability of fexofenadine x HCl after nasal administration of the microsphere formulation to rabbits was increased up to about 48% while that of the control solution was only about 3%. These results indicated that the HA microsphere formulation could further be developed into a clinically useful nasal delivery system of fexofenadine x HCl.
    European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 02/2010; 40(1):9-15. · 2.61 Impact Factor
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    ABSTRACT: A microemulsion system of docetaxel was prepared and evaluated for its solubilization capacity and oral bioavailability improvement. Based on a solubility study and pseudo ternary phase diagrams, microemulsions of about 30 nm in mean diameter were formulated with improved solubilization capacity towards the hydrophobic drug, docetaxel. The o/w microemulsion formulation (M-3) composed of Capryol 90 (oil), Cremophor EL (surfactant) and Transcutol (co-surfactant) enhanced the solubility of docetaxel up to 30 mg/mL, which maintained solubilization capacity for 24 h even after it was diluted 20 times with normal saline. The three formulations did not show significant difference in the in vitro lipid digestion study. Both the ultrafiltration and dialysis studies revealed that the release of 80% of docetaxel was released from the microemulsions within 12 h in vitro. Compared to the commercial product Taxotere (0.025 microg/cm(2)), the apical to basolateral transport of docetaxel across the Caco-2 cell monolayer from the M-3 formulation (Capryol 90/Cremophor EL/Transcutol=29.4:24.9:12.4, w/w) was significantly improved (0.624 microg/cm(2), p < 0.01). Moreover, the oral bioavailability of the M-3 formulation in rats (34.42%) rose dramatically compared to that of the orally administered Taxotere (6.63%). This increase in bioavailability was probably due to the combined effect of the enhancement in solubility, the inhibition of P-gp efflux system and the increase in permeability. These results encourage further development of docetaxel microemulsions as an oral drug delivery system.
    Journal of Controlled Release 09/2009; 140(2):86-94. · 7.63 Impact Factor
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    ABSTRACT: The synergic in vitro skin permeation enhancing-effect of N,N-diethyl-m-toluamide (DEET) and dodecylamine was investigated in order to develop a novel non-scrotal matrix-type transdermal delivery system of testosterone (TS). When DEET was loaded in DuroTak 87-2510 together with 2% TS and 3% dodecylamine, the in vitro rat skin permeation rate of TS synergistically increased as DEET concentration increased up to 0.5%. No further increase in permeation was observed thereafter and a plateau was observed up to 3.8% DEET. Moreover, compared to 0.5% DEET concentration, the addition of 3.8% of DEET in combination with 3% dodecylamine and 6% TS further increased the permeation rate of TS, and the maximum permeation rate of 11.21 microg/cm(2)/h was achieved. The in vitro skin permeation rates of TS from a transdermal delivery system of DuroTak 87-2510 containing 6% TS, 3% dodecyamine, and 3.8% DEET were in the following order: hairless mouse skin > rat skin > human cadaver skin. Assuming that a system with a surface area of 60 cm(2) is applied, the human cadaver skin permeation rate of 5.74 microg/cm(2)/h achieved in this study can be interpreted as being equivalent to delivering approximately 8. 27 mg of TS per day. Considering that the commercially available product (Testoderm TTS) for non-scrotal skin of the same surface area is designed to administer 5 mg of TS per day, the new formulation could maintain therapeutic plasma concentration of TS at a smaller surface area of 40 cm(2).
    Drug Delivery 07/2009; 16(5):249-53. · 2.02 Impact Factor
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    ABSTRACT: A redispersible dry emulsion (DE) formulation of atorvastatin calcium (AC) was developed to enhance the in vitro dissolution of AC, thereby increasing its gastrointestinal absorption. The spray-drying technology was used where Plurol Oleique CC 497 was chosen as the oil phase. Effects of carriers, surfactants, and homogenizers on the characteristics of DE containing AC were systematically investigated. The final formulation consisted of dextrin and Poloxamer 188 as carrier and surfactant, respectively, and was homogenized by a high pressure homogenizer before spray drying. The in vitro release of AC from the optimized DE was significantly higher than that of pure AC powder (76% vs. 30% at 24 hr). The in vitro intestinal absorption of AC from the DE formulation was 0.77 microg/cm(2) at 2 hr, which was a 2.33-fold increase compared to the pure unformulated AC powder. These results suggest that the oral dry emulsion formulation could improve the intestinal absorption of AC.
    Drug Delivery 02/2009; 16(1):30-6. · 2.02 Impact Factor
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    ABSTRACT: A simple and reliable high-performance liquid chromatographic (HPLC) method was developed for the determination of belotecan in the plasma, urine, and bile samples of rats. Belotecan was analyzed with HPLC using a C18 column with fluorescence detector. A mixture of acetonitrile-0.1 M potassium phosphate buffer at pH 2.4 (25:75, v/v) and 0.2% trifluoroacetic acid was used as the mobile phase. The lower limits of quantitation (LOQ) were 5 ng mL-1 for the plasma and 5 µg mL-1 for the urine and bile samples. The method has been readily applied for the routine pharmacokinetic study of belotecan in small laboratory animals.
    Analytical Letters 01/2009; 42(1):68-83. · 0.97 Impact Factor

Publication Stats

497 Citations
99.72 Total Impact Points

Institutions

  • 2011–2014
    • Dankook University
      • College of Pharmacy
      Eidō, North Chungcheong, South Korea
  • 2005–2012
    • Seoul National University
      • • Research Institute of Pharmaceutical Sciences
      • • College of Pharmacy
      Seoul, Seoul, South Korea
  • 2009–2011
    • Inje University
      • • College of Medicine
      • • Department of Medicine and Premedicine
      Kŭmhae, South Gyeongsang, South Korea
    • Dongseo University
      • Division of Health Science
      Pusan, Busan, South Korea
    • University of Kansas
      • Department of Pharmaceutical Chemistry
      Lawrence, KS, United States
  • 2010
    • Inje University Paik Hospital
      Sŏul, Seoul, South Korea
  • 2007–2009
    • Shenyang Pharmaceutical University
      • College of Pharmacy
      Feng-t’ien, Liaoning, China
  • 2007–2008
    • Pusan National University
      • College of Pharmacy
      Pusan, Busan, South Korea