• 한국임상약학회지
• /
• 제15권1호
• /
• pp.55-60
• /
• 2005

The aim of this study is to investigate the effect of naringin on the pharmacokinetics of tamoxifen in rats. Tamoxifen (10 mg/kg) was administered orally 0.5 h and 3 days after oral administration of naringin (5 mg/kg). The plasma concentrations of tamoxifen were increased significantly tv naringin compared to control. Absorption rate constant ($K_a$) of tamoxifen with naringin was increased significantly compared to that of the control. The areas under the plasma concentration-time curve (AUC) and the peak concentrations ($C_{max}$) of tamoxifen with naringin were significantly higher than those of the control. Consequently, the relative bioavailability (R.B${\%}$) of tamoxifen with naringin was 2-3-fold higher than the control, and absolute bioavailability (A.B${\%}$) of tamoxifen were significantly higher (p<0.05 with coadministration, p<0.01 with pretreatment) than those of the control. The increased bioavailability of tamoxifen in rats with naringin might be associated with the inhibition by naringin of an efflux pump P-glycoprotein and the first-pass metabolizing enzyme CYP3A4.

• 한국임상약학회지
• /
• 제15권1호
• /
• pp.50-54
• /
• 2005

The purpose of this study is to investigate the effect of aspirin on the pharmacokinetics of pranoprofen by oral coadministration of pranoprofen (5 mg/kg) with aspirin (5, 10 and 20 mg/kg) in Sprague-Dawley rats. After oral coadministration of pranoprofen with aspirin, the area under the plasma concentration-time curves (AUC) of pranoprofen was increased significantly by 10 mg/kg (p<0.05) and 20 mg/kg (p<0.01) of aspirin coadministration, and peak concentrations ($C_{max}$) of pranoprofen was increased significantly by coadministration of 20 mg/kg aspirin (p<0.05) compared to pranoprofen alone. Relative bioavailabilities (RB${\%}$) of pranoprofen in coadmistration were higher (from 1.42 to 1.67 fold) than control. The half-lives ($t_{1/2}$) of pranoprofen in coadministration were increased significantly (p<0.05) by 20-mg/kg aspirin. Based on these results, we might be considered that the pharmacokinetics of pranoprofen would be affected by coadministration of aspirin, by inhibit its metabolism in the liver and the tubular secretion of the kidney with the same acidic property. It should take into consideration in dosage regimen of pranoprofen when coadministration of pranoprofen with aspirin in treatment of rheumatoid arthritis.

• Journal of Pharmaceutical Investigation
• /
• 제41권4호
• /
• pp.249-253
• /
• 2011

To develop a sildenafil lactate-loaded solid self-emulsifying drug delivery system (SEDDS) with a fast onset of action and immediate action of erection, sildenafil lactate (0.3 g), which was prepared using a spray dryer, was dissolved in 4.7 g of the mixture of glyceryl monooleate/Transcutol/ Tween 20 (3/0.5/1, g). Its emulsion droplet size and pharmacokinetics in rabbits were evaluated compared with sildenafil citrate-loaded commercial tablet. The sildenafil lactateloaded SEDDS showed an emulsion droplet size of about 300 nm. In pharmacokinetics study, it gave significantly faster Tmax than did the commercial tablet. Thus, the sildenafil lactate-loaded SEDDS at the one-third drug dose compared to sildenafil citrate-loaded conventional tablet might induce a fast onset of action and immediate erection without enhanced bioavailability compared with the sildenafil citrate-loaded commercial tablet.

• Journal of Pharmaceutical Investigation
• /
• 제35권2호
• /
• pp.101-106
• /
• 2005

The pharmacokinetics of oral nifedipine (5 mg/kg) was studied in rabbits given after or simultaneously with naringin (1.5, 7.5 and 15 mg/kg, respectively). The area under the plasma concentration-time curve (AUC) and the peak concentration $(C_{max})$ of nifedipine coadministered or pretreated with naringin were significantly increased (p < 0.05, coad.; p < 0.01, pret.) compared with the control group. The absolute bioavailability (AB%) of nifedipine was significantly (p < 0.05, coad.; p < 0.01, pret.) higher by 22.3 - 28.1 % compared to the control (17.9%). The relative bioavailability (RB%) of nifedipine was higher by 1.24 - 1.43 times (coad.) and 1.32 -1.57 times (pret.) than those of the control, showing that preatreatrnent of naringin was more effective than that of the coadministration of naringin. Naringin did not show significant effect on the Tmax and $t_{1/2}$ of nifedipine. It is suggested that naringin may alter pharmacokinetic paramiters of nifedipine by inhibition of P-glycoprotein efflux pump and its first-pass metabolism. The dosage of nifedipine should be adjusted when it is administered with naringin in a clinical situation.

• Journal of Applied Biological Chemistry
• /
• 제58권4호
• /
• pp.363-368
• /
• 2015

The pharmacokinetics of florfenicol were studied in healthy and vibriosis-infected large yellow croaker (Pseudosciaena crocea) following administration of a single oral dose of $20mg{\cdot}kg^{-1}$ at $25{\pm}2^{\circ}C$. After oral administration, florfenicol levels in tissues (liver, kidney, muscle, serum, and skin) were analyzed using high-performance liquid chromatography. A two-compartment open model was used to describe the pharmacokinetics of florfenicol following oral administration. Compared to the healthy group, the absorption rate of vibriosis-infected fish significantly decreased, peak-time ($T_{max}$) delayed, maximum concentration ($C_{max}$) declined, total body clearance decreased, the elimination half-life ($T_{1/2{\beta}}$) was extended, and the area under the curve increased. These results indicate that a $20mg{\cdot}kg^{-1}$ oral dose of florfenicol administered once daily continuously for 4 or 5 days can be used for the treatment of Vibrio alginolyticus infection in large yellow croaker (Pseudosciaena crocea).

• Journal of Pharmaceutical Investigation
• /
• 제36권3호
• /
• pp.157-160
• /
• 2006

This study investigated the effect of clarithromycin on the pharmacokinetics of ambroxol in rats. The pharmacokinetic parameters of ambroxol in rats were determined after the oral administration of ambroxol (12 mg/kg) in the presence or absence of clarithromycin (5 or 10 mg/kg). Compared with the control (given ambroxol alone), coadministration of clarithromycin significantly (p<0.05 at 5 mg/kg; p<0.01 at 10 mg/kg) increased the area under the plasma concentration-time curve (AUC), peak plasma concentrations $(C_{max})$ and absorption rate constant $(K_a)$ of ambroxol. Clarithromycin increased the AUC of ambroxol in a dose dependent manner within the dose range of 5 to 10 mg/kg. The absolute bioavailability (AB%) of ambroxol in the presence of clarithromycin was significantly higher than that of the control (p<0.05 at 5 mg/kg; p<0.01 at 10 mg/kg), and the relative bioavailability (RB%) of ambroxol with clarithromycin was increased by 1.32-to 1.71-fold. However, there were no significant changes in time to reach peak concentration $(T_{max})$ and terminal half-life $(T_{1/2})$ of ambroxol in the presence of clarithromycin. Coadministration of clarithromycin enhanced the bioavailability of ambroxol, which may be due to the inhibition of intestinal and hepatic metabolism of ambroxol by CYP 3A4. Further studies for the potential drug interaction are necessary since ambroxol is often administrated concomitantly with clarithromycin in humans.

• Journal of Pharmaceutical Investigation
• /
• 제25권2호
• /
• pp.117-123
• /
• 1995

For the effective administration of narcotic antagonist, the application of sustained release implantable systems with biodegradable polyphosphazene was examined. Using poly[(diethyl glutamate)-co-(ethyl glycinate) phosphazene], the implantable devices containing naloxone hydrochloride were prepared and in vivo implantation studies were carried out subcutaneously in rat and rabbit with this preparation for the biocompatibility and pharmacokinetics. The histological finding in rats at initial time period was the inflammation that occurred focally around the implants, but they were showed subsequent mild and limited chronic inflammations and the irreversible changes such as necrosis and degeneration of the muscle or connective tissues were not observed. Therefore the placebo and naloxone implants are considered to be biocompatible formulations histologically. In pharmacokinetic studies, the release of naloxone from the naloxone implants into blood plasma was maintained in 192 hours, but the initial burst effect was observed. If this problem was solved, the application for the narcotic antagonist sustained release systems can be expected.

• 약학회지
• /
• 제50권2호
• /
• pp.118-123
• /
• 2006

The aim of this study was to investigate the effect of fluvastatin on the pharmacokinetics of diltiazem and its active metabolite, desacetyldiltiazem, in rats. Pharmacokinetic parameters of diltiazem and desacetyldiltiazem were deter-mined after an oral administration of diltiazem (15 mg/kg) to rats pretreated with fluvastatin (0.5 and 1.5 mg/kg). Compared with the control (given diltiazem alone), the pretreatment of fluvastatin significantly (p<0.05) increased the area under the plasma concentration (AUC), peak plasma concentration $(C_{max})\;and\;K_a$ of diltiazem. Relative bioavailability $(RB\%)$ of diltiazem increased from 1.36- to 1.55-fold. However there were no significant changes in $t_{max},\;K_{el}\;and\;t_{1/2}$ of diltiazem. The pretreatment of fluvastatin also altered the pharmacokintic parameters of desacetyldiltiazem. The pretreatment of fluvastatin (1.5 mg/kg) significantly (p<0.05) increased the AUC of desacetyldiltiazem, whereas the metabolite parent ratio (MR) of desacetyldiatlazem was decreased significantly (p<0.05), suggesting that fluvastatin might inhibit the metabolism of diltiazem. The pretreatment of fluvastatin enhanced the bioavailability of diltiazem in a dose dependent manner at doses ranging from 0.5 to 1.5 mg/kg. further studies for the drug Interaction will be needed in the clinical trials when dilitazem is administrated concomitantly with fluvastatin in humans.

• 약학회지
• /
• 제44권6호
• /
• pp.539-544
• /
• 2000

Many diabetic patients develop serious complications during the course of the disease, including cardiovascalar disorders, nepropathy, neuropathy and retinopathy. Because some physiological changes occurring in diabetes mellitus patients could alter the pharmacokinetics of drugs used to treat the disease, the pharmacokinetics of gentamycin was investigated after intravenous administration (2 mg/kg) to control rabbits and acute or chronic alloxan-induced diabetes mellitus rabbits (AIDRs). After intravenous administration, the serum concentrations of gentamycin were significantly higher between 6 and 12 hr in chronic AIDRs compared with those in control rabbits. The AUC was significant greater in chronic ($31.91\;{\pm}\;3.76\;{\mu}g/ml{\cdot}hr$) AIDRs than that in control ($21.60\;{\pm}\;2.45\;{\mu}g/ml{\cdot}hr$) rabbits. Total body clearance (CLt) in AIDRs were significantly decreased compared with that in control rabbits. Cumulative urinary excretion of gentamycin was decreased, although not significantly, in AIDRs compared with that in control rabbits.

• 약학회지
• /
• 제48권4호
• /
• pp.226-230
• /
• 2004

The pharmacokinetics of orally administered paclitlxel (50 mg/kg) was studied in six rabbits after 1hr pretreatment (2.0 mg/kg and 10 mg/kg) of tetramethoxyflavone or coadministration of (2.0 mg/kg, 10 mg/kg and 20 mg/kg) tetramethoxyflavone. The area under the plasma concentration-tine curve (AUC) and plasma concentration of paclitaxe1 coadministered with tetramethoxyflavone (10 mglkg) were increased significantly (p<0.05) compared with control. However, coadministration of tetramethoxyflavone (2 and 20 mg/kg) showed no significant effect on the pharmacokinetic parameters of paclitaxel. Pretreatment with tetramethoxyflavone significantly (p<0.05) increased the plasma concentration of paclitaxel. The area under the plasma concentration-time curve (AUC) and the peak concentration (C$_{max}$) of paclitaxel pretreated with tetramethoxyflavone were increased significantly (p<0.01, p<0.05) compared with control. The terminal half. life of paclitaxel pretreated with tetramethoxyflavone (2 mg/kg and 10 mg/kg) was significantly (p<0.05) prolonged compared with control. Pretreatment with tetramethoxyflavone (2.0 mg/kg, 10 mg/kg) significantly (p<0.01, p<0.05) increased the absolute bioavailability of paclitaxel compared with the control (154∼179%). On the basis of the results, it might be considered that tetramethoxyflavone may inhibit cytochrome P450 or P-glycoprotein efflux pump which are engaged in paclitaxel metabolism, result in increased AUC and t$_{1}$2/ of paclitaxel. However, further study should be conducted to clarify the roles of cytochrome P450 and P-glycoprotein on paclitaxel bioavailability with/or without tetramethoxyflavone. P-glycoprotein on paclitaxel bioavailability with/or without tetramethoxyflavone.