• Biomolecules & Therapeutics
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• v.1 no.2
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• pp.204-210
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• 1993

The distribution and excretion of DWC-751, a new cephalosporin, were examined in rats and mice following a single intravenous administration. DWC-751 in plasma and urine was determined by both HPLC and microbiological assay. The plasma concentration of the drug declined biexponentially. The initial and terminal half lives of the drug were 3.0 and 28.3 min, respectively. Binding of the drug to plasma proteins was 42.3%. The distribution volume at steacly-state ($Vd_{ss}$) was only 0.341 ι/kg, which is well correlated with the low n-octanol/water partition coefficient of the drug ($K_{o/w{\cong}0$) Actually, the drug was distributed to liver, kidney and lung with very low organ/plasma concentration ratio. The drug, was excreted mainly via renal excretion, i.e., the total($CL_T$) and apparent renal($CL_{R}$) clearances of the drug were 10.8 and 7.5 ml/min/kg, respectively.

• Journal of Pharmaceutical Investigation
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• v.18 no.2
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• pp.49-53
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• 1988

Pivaloyloxymethyl ester of piperacillin was synthesized by reacting sodium piperacillin with chloromethyl pivalate, and its chemical structure was determined by infrared and $^1H$ nuclear magnetic resonance spectroscopic methods. The pharmaceutical properties of the ester were investigated to assess its potential as a novel prodrug of piperacillin. The interface transfer of piperacillin and the ester was studied in a two-phase in vitro system composed of aqueous pH buffers and n-octanol. The ester was more lipophilic, and less water soluble above pH 4.0 than piperacillin. Significant antibacterial activity was not observed in the ester in vitro, but the ester was hydrolyzed into the parent drug in the rat liver homogenate. The serum levels of orally administered ester suspension containing 0.1% Tween 80 were measured in rabbits. It was found that the ester showed higher blood level, comparing with no observation of piperacillin in serum, but the time reaching the maximum serum concentration was 5 hr.

• Archives of Pharmacal Research
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• v.9 no.1
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• pp.49-54
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• 1986

Effect of sodium taurodeoxycholate (TDC) infused intravenously on the pharmacokinetics of methylene blue (MB) was studied in the rat to investigate the role of ion-pair complexation in the body on drug elimination and disposition. Distribution volume (Vd) of MB was increased significantly (p< 0.05) by TDC infusion. Considering together with the fact that apparent partition coefficient (APC) of MB between phosphate buffer (pH 7.4) and n-octanol was increased markedly by TDC, the increase in Vd seemed to be the result of decreased polarity of MB by ion-pair formation with TDC. But total body clearance (CLt) and biliary excretion clearance (CLbil) of MB were not increased significantly by TDC.

• Journal of Pharmaceutical Investigation
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• v.19 no.1
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• pp.21-27
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• 1989

Kinetic and thermodynamic aspects of the interface transfer of cefoperazone and its pivaloyloxymethyl ester were studied in a two-phase system composed of aqueous buffers and n-octanol by using the absolute reaction rate theory. In terms of the net thermodynamic parameters for the process, ${\Delta}S$ increased and ${\Delta}F$ decreased as the lipophilicity increased. With the increased ratio of forward $(k_f)$ to backward rate constants $(k_b)$, the ester was more lipophilic than cefoperazone, but the aqueous solubility was reduced.

• Journal of the Korean Ceramic Society
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• v.31 no.1
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• pp.1-10
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• 1994

Monodispersed alumina and Mg-doped alumina fine particles were prepared by controlled hydrolysis of alkoxides. Aluminium alkoxide and magnesium alkoxide were dissolved into complex solvent which was composed of hydrophobic n-octanol and hydrophilic acetonitrile. Hydroxypropyl cellulose(HPC) was used as a dispersant for the alumina particles. The size of these prepared powders was approximately 0.3 ${\mu}{\textrm}{m}$. In the case of sintering above 100$0^{\circ}C$, most of these prepared powders were transformed to $\alpha$-alumina. The relative density of the sintered body of these prepared powders at 1$600^{\circ}C$ was 98%. The sintered body of the Mg-doped alumina powder had more uniform grain size than that of the undoped alumina podwer.

• Biotechnology and Bioprocess Engineering:BBE
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• v.9 no.3
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• pp.207-211
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• 2004

Predispersed solvent extraction (PDSE) of succinic acid with Tri-n-octylamine (TOA) dissolved in 1-octanol from aqueous solutions of 50 g/L succinic acid was examined. It was found that the equilibrium data in PDSE was equal to that in conventional solvent extraction in spite of the lack of mechanical mixing in PDSE. The influence of salts on succinic acid extraction and the stability of colloidal liquid aphrons (CLAs) were also investigated. Results indicated that in the presence of sodium chloride, less succinic acid was extracted by CLAs and the stability of CLAs decreased. However, the stability of CLAs was sufficient to make PDSE practically applicable to real fermentation broth, considering the concentration range of salts in the fermentation process for succinic acid.

• YAKHAK HOEJI
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• v.27 no.2
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• pp.125-131
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• 1983

Whether ($AB_{w}$) may be neglected against ($A_{w}^{+}$) in the calculation of the extraction coefficient of ion-pairs was criticized by both experiments and theoretical consideration, where ($AB_{w}$) and ($A_{w}^{+}$) mean the molar concentration of ion-pair AB and cation $A^{+}$ in the aqueous phase. Ion-pair complexes were partitioned between phosphate buffer (pH 7.4) and n-octanol. Tetrabutylammonium, isopropamide and methylene blue were selected as cations and benzoic acid, p-toluenesulfonic acid, salicylic acid and taurodeoxycholic acid were selected as counter ions (anions). As a result, conventional methods which assume no existence of ($AB_{w}$) were proven to lack generality. The equation proposed in my earlier report was confirmed to be valid as a general method.

• Archives of Pharmacal Research
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• v.17 no.3
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• pp.182-189
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• 1994

The effect of lipophilicity on the mechanisms of drug absorption through biomembranes was investigated empolying HPLC system and the fluorescence technique. Human erythrocyte ghost membranes were used as a model biomembrane. A series of four parabens (methyl, ethyl, rpopyl, and butyl) and p-hydroxybenzoic acid were used as the model drugs for lipophilicities and their partition coefficients were measured in Sorensen's phosphate buffer solution (pH 5)/octanol system. Absorption amount of parabens through erythrocyte ghost membranes increased with an increase of lipophilicity resulted from the addition of methylene group to the n-alkyl chain of parabens. And the effect of parabens on the fluidity of ghost membrane also increased with an increase of their lipophilicities.

• YAKHAK HOEJI
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• v.30 no.3
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• pp.128-138
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• 1986

Three newly synthesized alkanol esters of d-2-(6-methoxy-2-naphthyl) propionic acid, NAPROXEN were examined for physicochemical properties and biopharmaceutical characteristics. These esters were very stable in solid state, but more than 90% of these esters were hydrolysed to the parent, naproxen in rabbit's liver hornogenates. They showed higher dissolution rate in the artificial gastric and intestinal juice, and significantly greater partition coefficient in n-octanol, when compared with naproxen. The absorption rate constants of these esters were increased, while the elimination rate constants were decreased, comparing with naproxen. The ulcerogenic doses on gastric and intestinal mucosa were increased remarkably, and the antiinflammatory dose against carrageenininduced edema on rat hind paw was decreased markedly in these esters, and thus the safety indexes of these esters were higher than that of naproxen.

• 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.