• 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.

• Archives of Pharmacal Research
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• v.28 no.10
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• pp.1190-1195
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• 2005

The objective of this study was to develop an assay for mequitazine (MQZ) for the study of the bioavailability of the drug in human subjects. Using one mL of human plasma, the pH of the sample was adjusted and MQZ in the aqueous phase extracted with hexane; the organic layer was then evaporated to dryness, reconstituted and an aliquot introduced to a gas chromatograph/mass spectrometer (GC/MS) system with ion-trap detector. Inter- and intra-day precision of the assay were less than 15.1 and $17.7{\%}$, respectively; Inter- and intra-day accuracy were less than 8.91 and $18.6{\%}$, respectively. The limit of quantification for the current assay was set at 1 ng/mL. To determine whether the current assay is applicable in a pharmacokinetic study for MQZ in human, oral formulation containing 10 mg MQZ was administered to healthy male subjects and blood samples collected. The current assay was able to quantify MQZ levels in most of the samples. The maximum concentration ($C_{max}$ was 8.5 ng/mL, which was obtained at 10.1 h, with mean half-life of approximately 45.5 h. Under the current sampling protocol, the ratio of $AUC_{t{\rightarrow}last}$ to $AUC_{t{\rightarrow}{\infty}}$ was $934{\%}$, indicating that the blood collection time of 216 h is reasonable for MQZ. Therefore, these observations indicate that an assay for MQZ in human plasma is developed by using GC/MS with ion-trap detector and validated for the study of pharmacokinetics of single oral dose of 10 mg MQZ, and that the current study design for the bioavailability study is adequate for the drug.

• Archives of Pharmacal Research
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• v.26 no.7
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• pp.569-574
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• 2003

Controlled-release amitriptyline pellets (ATP) were formulated and its oral bioavailability was assessed in human volunteers after oral administration under fasting conditions. Core pellets were prepared using a CF granulator by two different methods (powder layering and solvent spraying) and coated with Eudragit RS or RL 100. Physical characteristics and dissolution rates of core pellets and coated pellets were evaluated to optimize the formulation. Powder layering method resulted in a better surface morphology than solvent spraying method. However, physical properties of the products were poorer when prepared by powder layering method with respect to hardness, friability and density. The dissolution profile of amitriptyline coated with Eudragit RS 100 was comparable to that of commercially available amitriptyline enteric-coated pellets ($Saroten^{\circledR}$ retard). After the oral administration of both products at the dose of 50 mg, the mean maximum concentrations ($C_{max}$) were 36.4 and 29.7 ng/mL, and the mean areas under the concentration-time curve ($AUC_{0-96}$) were 1180.2 and 1010.7 ng.h/mL for ATP and Saroten retard, respectively. The time to reach the maximum concentrations ($T_{max}$) was 6 h for both formulations. Statistical evaluation suggested that ATP was bioequivalent to Saroten retard.

• Journal of Pharmaceutical Investigation
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• v.24 no.4
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• pp.265-271
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• 1994

Cefazolin ethoxycarbonylethyl ester (CFZ-ET) was synthesized to improve oral absorption and bioavailability of the parent drug by esterification of sodium cefazolin (CFZ-Na). The successful synthesis of CFZ-ET was identified with analysis of UV spectra, FT-lR spectra and NMR spectra. Partition coefficient studies showed that CFZ-ET was more lipophilic than CFZ-Na and the ester was hydrolyzed into the parent drug in vivo. Although CFZ-ET did not have antimicrobial activity in vitro, the plasma taken after the oral administration of CFZ-ET had antimicrobial activity. Based on above observations, CFZ-ET might be rapidly hydrolyzed to CFZ in the body. Therefore, it may be concluded that CFZ-ET could be a novel prodrug of CFZ which can improve the bioavailability of CFZ-Na.

• Journal of Pharmaceutical Investigation
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• v.35 no.5
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• pp.349-353
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• 2005

This study reports the pharmacokinetics of a novel histone deacetylase inhibitor, SD-0542, in rats after i..v. and oral administration. SD-0542 was injected intravenously at doses of 10, 20, and 40 mg/kg. The terminal elimination half-life $(t_{1/2})$, systemic clearance (Cl), and steady-state volume of distribution $(V_{ss})$ remained unaltered as a function of dose, with their values ranging from 2.0-2.5 hr, 157.2-214.1 ml/min/kg, and 11.1-17.5 L/kg, respectively, whereas, the initial serum concentration $(C_0)$ and AUC increased linearly as the dose was increased. Renal excretion of SD-0542 was minimal. Oral pharmacokinetic studies were conducted in rats at a dose of 20 mg/kg. The $T_{max}$, Cl/F, $V_{z}/F$, and $t_{1/2}$ were 2.0 hr, 92864 ml/min/kg, 16331 L/kg, and 2.0 hr, respectively. Taken together, SD-0542 showed linear pharmacokinetics over the i.v. bolus dose range studied. SD-0542 was poorly absorbed, with the absolute oral bioavailability of 0.9%.

• Journal of Pharmaceutical Investigation
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• v.29 no.2
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• pp.99-103
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• 1999

Self-Emulsifying System(SES), an isotropic mixture of oil and surfactant which forms oil-in-water emulsion, is expected to improve in vitro drug dissolution and enhance in vivo drug absorption. A poorly water soluble drug, ibu-profen(IBP) was incorporated into the SES to improve absorption, and enhance bioavailability of drug. Medium chain triglyceride, glyceryl tricaprylate(GTC) as an oil, and Tween 85 as a surfactant were used to formulate SES. To characterize SESs with various concentrations of Tween 85, the phase separation and solubility of IBP-SEDDS containing IBP as a function of Tween 85 concentration were conducted, and the particle size was measured using photon correlation spectroscopic method. The SES with optimal concentration of Tween 85(35%(w/w)) was selected based on its high drug loading, small particle size and low surfactant concentration. After an oral administration of IBP-SEDDS and IBP suspension in methyl cellulose equivalent to 40.0 mg/kg to rats, the pharmacokinetic parameters were compared. The $C_{max}(163.17\;vs\;88.82\;{\mu}g/ml)$, $AUC(12897.01\;vs\;8751.13\;{\mu}g\;min/ml)$ and Bioavailability(86.44 vs 58.65%) significantly increased but $T_max(10\;vs\;20\;min)$ was significantly advanced. The current SEDDS containing IBP provide an alternative to improve an oral bio-availability of IBP.

• YAKHAK HOEJI
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• v.39 no.3
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• pp.223-230
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• 1995

The phannacokinetics and tissue distribution of DWQ-013, a new quinolone, were examined in rats and mice following a single intravenous and oral administration. DWQ-013 in plasma and urine was determined by both HPLC and microbiological assay. The plasma concentration of the drug declined biexponentially. The terminal half life of the drug was 11.11$\pm$0.14 hour after intravenous dosing. The volume of distribution at terminal elimination phase(Vd$_\beta$) and total clearance of the drug were 1.29$\pm$0.15 l/kg and 0.78$\pm$0.09 l/h/kg. The bioavailability of DWQ-013 after oral administration was 56.0% (HPLC) and 77.2%(bioassay), respectively. Twelve-hour urinary recovery of drug was measured by HPLC and bioassay to 0.035$\pm$0009% and 4.71$\pm$066% after oral dosing, to 0.055$\pm$0.014% and 7.65$\pm$1.53% after intravenous dosing, which may indicate the presence of biologically active metabolites. Binding of the drug to plasma proteins ranged from 97%~99% at various concentrations. The drug was highly distributed in order of liver, kidney and lung after 1.5 hours in mice.

• Korean Journal of Clinical Pharmacy
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• v.18 no.1
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• pp.6-10
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• 2008

This study investigated the effect of long-term administration of pioglitazone on the pharmacokinetics of verapamil in rats. Pharmacokinetic parameters of verapamil were determined after oral administration of verapamil (9 mg/kg) in rats coadministered pioglitazone (0.5 mg/kg) or pretreated with pioglitazone (0.5 mg/kg) for 3 and 9 days. Compared to oral control group, the presence of pioglitazone significantly (p<0.05) increased the area under the plasma concentration-time curve (AUC) of verapamil by 48.6% (coad), 61.1% (3 days) and 56.5% (9 days), and the peak concentration($C_{max}$) by 65.1% (coad), 76.8% (3 days) and 66.4% (9 days). The absolute bioavailability (AB%) of verapamil was significantly (p<0.05) higher by 6.2% (coad), 6.7% (3 days), 6.5% (9 days) compared to control (4.2%), and presence of pioglitazone was no significant change in the terminal half-life ($t_{1/2}$) and the time to reach the peak concentration($T_{max}$) of verapamil. Our results indicate that pioglitazone significantly enhanced oral bioavailability of verapamil in rats, implying that presence of pioglitazone could be effective to inhibit the CYP3A4-mediated metabolism of verapamil in the intestine. Drug interactions should be considered in the clinical setting when verapamil is coadministrated with pioglitazone.

• YAKHAK HOEJI
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• v.39 no.6
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• pp.577-584
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• 1995

On the combination of antacid, the pharmacokinetics and gastric adhesion of [$^{14}c$]aceglutamide aluminium complex([$^{14}C$]AGA) were examined in rats. Specially, this study was focused on the drug interaction that the co-administration of antacid may affect the oral absorption and gastric adhesion of aceglutamide aluminium complex(AGA). In the study of the oral co-administration of [$^{14}C$] AGA and antacid(aluminium hydroxide and magnesium hydroxide(AM)), the radioactivity of plasma and urinary recovery was lower than that of [$^{14}C$]AGA alone administered group. However, the cumulative recovery of radioactivity in feces was increased significantly. The comparative bioavailability of [$^{14}C$] AGA from the plasma concentration-time curve and urinary recovery was about 60%. In vitro, the effect of antacid on the gastric adhesion of AGA was not significatly different between AGA and AGA/antacid treatment. And it accorded well with the result of in vivo experiment. In conclusion, on the combination of antacid, the oral absorption of AGA was decreased by the gastric adhesion was not affected in respect of drug interaction.

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