• Archives of Pharmacal Research
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• v.29 no.4
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• pp.333-338
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• 2006

The aim of this study was to investigate the effect of morin on the bioavailability of nimodipine after administering nimodipine (15 mg/kg) orally to rabbits either co-administered or pretreated with morin (2, 10 and 20 mg/kg). The plasma concentrations of nimodipine in the rabbits pretreated with morin were increased significantly (p<0.05 at 10 mg/kg, p<0.01 at 20 mg/kg) compared with the control, but the plasma concentrations of nimodipine co-administered with morin were not significant. The areas under the plasma concentration-time curve (AUC) and the peak concentrations $(C_{max})$ of the nimodipine in the rabbits pretreated with morin were significantly higher (p<0.05 at 10 mg/kg, p<0.01 at 20 mg/kg), but only the $C_{max}$ of nimodipine coadministered with morin 10 mg/kg was increased significantly (p<0.05). The absolute bioavailability $(A.B\%)$ of nimodipine in the rabbits pretreated with morin was significantly (p<0.05 at 10 mg/kg, p<0.01 at 20 mg/kg) higher $(54.1-65.0\%)$ than the control $(36.7\%)$. The increased bioavailability of nimodipine in the rabbits pretreated with morin might have been resulted from the morin, which inhibits the efflux pump P-glycoprotein and the first-pass metabolizing enzyme by cytochrome P-450 3A4 (CYP 3A4).

• Journal of Pharmaceutical Investigation
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• v.14 no.1
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• pp.19-30
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• 1984

The pharmaceutical characteristics of solid indoprofen inclusion complex such as dissolution, permeation through a cellophane membrane, model analysis of interfacial tranesfer, absorption behaviors in rat intestine, and the plasma concentration of indoprofen after oral administrations to rabbits were examined in comparison with those indoprofen alone. The inclusion complex obtained by freeze-drying method showed the higher dissolution rate and membrane permeability among the test powders, and increased significantly the amont of indoprofen absorbed in rat intestine and the levels of plasma concentration of indoprofen after oral adminstrations to rabbits. The increase of bioavailability of $indoprofen-{\beta}-cyclodextrin$ complex was considered due to the increased solubility and dissolution rate of solid powder form.

• Journal of Pharmaceutical Investigation
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• v.40 no.6
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• pp.339-345
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• 2010

Fenofibrate has been used for many years to lower cholesterol levels and its pharmacokinetic profile is well understood. However, due to its low solubility in water, it has low bioavailability after oral administration. In order to improve the dissolution rate, fenofibrate was formulated into a self-microemulsifying drug delivery systems (SMEDDS). We used pseudo-ternary phase diagrams to evaluate the area of microemulsification, and an in vitro dissolution test was used to investigate the dissolution rate of fenofibrate. The optimized formulation for in vitro dissolution assessment consisted of Lauroglycol FCC (60%), Solutol HS 15 (27%), and Transcutol-P (13%). The mean droplet size of the oil phase in the microemulsion formed from the SMEDDS was about 130 nm. The dissolution rate of fenofibrate from SMEDDS was significantly higher than that of the reference tablet. Our studies suggested that the fenofibrate containing SMEDDS composition can effectively increase the solubility and oral bioavailability of poorly water-soluble drugs.

• YAKHAK HOEJI
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• v.47 no.5
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• pp.331-338
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• 2003

A butyrolactone ester of cefazolin (CFZ-BTL) was synthesized by the esterification of cefazolin (CFZ) with $\alpha$-bromo-${\gamma}$-butyrolactone. The synthesis was confirmed by the spectroscopic analysis. The CFZ-BTL was more lipophilic than the CFZ when assessed by n-octanol/water partition coefficients at various pH. The CFZ-BTL itself did not show any antimicrobial activity in vitro, but after oral administration of CFZ-BTL to rabbits, exerted significant anti-microbial activity in serum samples when measured by the inhibion zone method in nutrient agar plates, due to conversion of CFZ-BTL to an active metabolite, probably CFZ, in the body. The CFZ-BTL was also converted into CFZ as confirmed by in vitro incubation study, with tissue homogenates (liver, blood and intestine) of rabbits. The liver showed the fastest conversion rate, probably via the hydrolysis mechanism. In vivo metabolism of CFZ-BTL to CFZ was also confirmed in vivo serum samples by HPLC. The oral bioavailability of CFZ-BTL in rabbits was 1.6-fold increased when compared to CFZ, resulting from followed by enhanced lipophilicity increased passive absorption in the intestine.

• Proceedings of the PSK Conference
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• 2001.10a
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• pp.310.1-310.1
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• 2001

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.240.3-241
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• 2003

The purpose of this trial was to determine pharmacokinetic parameters and to characterize bioavailability of levosulpiride after oral administration in Korean healthy male volunteers. Thirty subjects were received a single oral dose of a tablet (Isomeric$\^$\ulcorner/) containing 25 mg of levosulpiride. The plasma concentrations of levosulpiride were measured by a validated FLD-HPLC method and compared with those reported in the literature. Levosulpride was absorbed slowly, revealing peak concentrations between 4 and 6 hr after oral administration. (omitted)

• Journal of Pharmaceutical Investigation
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• v.39 no.5
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• pp.327-331
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• 2009

5-HT$_{2C}$ receptors have been considered as therapeutic targets for the treatment of various central nervous system disorders such as depression, anxiety, epilepsy, schizophrenia and sleep disorders. We chemically synthesized KKHQ80109 (K09) and KKHQ80114 (K14), selective 5-HT$_{2C}$ agonists, with the purpose of developing therapeutic agents for the treatment of obesity. The objective of this work is to investigate pharmacokinetic parameters and bioavailability of K09 and K14 in rats given orally or intravenously. Oral administration of 20 mg/kg K09 results in 4.11 hr of the terminal half-life and 89.16 ng/mL of C$_{max}$ at 5.00 hr (T$_{max}$). The terminal half-life of K14 was 3.83 hr with 215.81 ng/mL of C$_{max}$ at 3.33 hr (T$_{max}$) after oral dosing of 20 mg/kg K14, indicating that K14 is more rapidly absorbed than K09. Bioavailability showed 0.17-0.21 for K09 and 0.19-0.23 for K14. Urinary excretion of parent K09 and K14 was less than 1%, indicating that K09 and K14 undergo very extensive hepatic metabolism.

• Journal of Pharmaceutical Investigation
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• v.32 no.1
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• pp.27-33
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• 2002

A self-microemulsifying drug delivery system(SMEDDS) composed of Cremophor $EL^{\circledR},\;Labrasol^{circledR}$, and Lauroglycol $FCC^{circledR}$ was prepared for the enhancement of solubility, dissolution rate and bioavailability of ibuprofen(IBP), which is water-insoluble but soluble in oils and surfactants. Phase diagram with various regions including microemulsion area was depicted. The SMEDDS was encapsulated in soft gelatin capsules and their dissolution characteristics in various media were observed in comparison to the generic products commercially available in the market. Soft capsules of SMEDDS formulation showed better dissolution profiles, especially in acidic condition, than the others. For the period of 1 hr dissolution in pH 1.2 medium, it reached over 70% dissolution from soft capsules, compared to less than 40% dissolution from commercial reference tablets. On the other hand, in vivo pharmacokinetic parameters were obtained after oral administrations of different IBP preparations to Sprague Dawley rats. SMEDDS formulation showed higher $C_{max}$ and greater $AUC_{0-5hr}$ than the suspension of reference tablet or IBP powder. Therefore, it is possible to conclude that a newly developed soft capsules employing SMEDDS provides an alternative preparation to improve oral bioavailability of IBP.

• Korean Journal of Clinical Pharmacy
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• v.1 no.1
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• pp.9-14
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• 1991

Inclusion complexes of piroxicam with $\alpha,\;\beta\;and\;\gamma- cyclodextrins$ were prepared and suspended to enhance the bioavailability of piroxicam. A quantitative analysis was employed HPLC for the determination of piroxicam in the rabbit serum after a single oral dose in suspension of piroxicam and each of inclusion complexes of piroxicam with $\alpha,\;\beta\;and\;\gamma- cyclodextrins$, respectively. The bioavailability and serum level of piroxicam exhibited the highest in piroxicam clathrated $\beta-cyclodextrin$ than both piroxicam and the other complexes administered. and the total area under the curve of serum concentration versus time for their inclusion complexes were larger than that of piroxicam.

• Journal of Pharmaceutical Investigation
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• v.18 no.3
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• pp.99-105
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• 1988

Inclusion complex formation of furosemide with ${\beta}-cyclodextrin({\beta}-CyD)$ in solid state was confirmed by X-ray diffractometry, IR spectroscopy and differential scanning calorimetry (DSC). The solid complexes of ${\beta}-CyD$ with furosemide in molar ratio of 2 : 1 were prepared by solvent evaporation method. The photodegradation of furosemide in alkaline solution under the light and the hydrolysis of furosemide in acidic solution were not inhibited by complex formation with ${\beta}-CyD$. However, the bioavailability of furosemide was improved by complex formation with ${\beta}-CyD$ after oral administration to rats.