• Korean Circulation Journal
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• 제54권3호
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• pp.113-123
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• 2024

Background and Objectives: Previous studies have reported an association between impaired renal function and poor outcomes after radiofrequency catheter ablation in patients with atrial fibrillation (AF). However, outcomes of cryoballoon ablation (CBA) in patients with renal insufficiency are not fully elucidated. This study aimed to compare outcomes of CBA in AF patients with chronic kidney disease (CKD) versus those without CKD and to assess changes in renal function over 12 months following CBA. Methods: A total of 839 patients (65.1% with non-paroxysmal AF [PAF]) who underwent de novo CBA were prospectively enrolled. We divided patients into two groups based on creatinine clearance rate (CCr) and performed intracardiac echocardiography (ICE)-guided contrast agent-free CBA. Results: In comparison with patients without CKD (CCr >50, n=722), those with CKD (CCr ≤50, n=117) were older and predominantly female, had a lower body mass index, and showed a higher prevalence of heart failure and hypertension. Mean CHA₂DS₂-VAS score was significantly higher in CKD group than in non-CKD group. Procedure-related complications were not significantly different between two groups. During a mean follow-up period of 25.4±11.9 months, clinical recurrence occurred in 182 patients (21.7%) and not significantly different between two groups. In multivariate analysis, non-PAF and left atrial size were independent predictors of AF recurrence. CCr levels significantly improved over 12 months after CBA in CKD group. Conclusions: ICE-guided contrast-agent-free CBA showed comparable long-term clinical outcomes without increasing procedure-related complications and improvement of renal function over 12 months following CBA in AF patients with CKD.

• 대한수의학회지
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• 제51권4호
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• pp.253-257
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• 2011

Amikacin is a semisynthetic derivative of kanamycin and primarily active against aerobic Gram-negative-pathogens with limited activity against Gram-positive bacteria. Meager study was reported on pharmacokinetic data on multi-days administration of amikacin. Hence, pharmacokinetics study was done in five clinically healthy goats (n = 5), after intravenous bolus injection of amikacin sulfate at the dose rate of 10 mg/kg body weight daily for three consecutive days. The amikacin concentrations in plasma and pharmacokinetics-parameters were analyzed by using microbiological assay technique and noncompartmental open-model, respectively. The mean peak plasma concentrations (Mean ${\pm}$ SD) of amikacin at time zero ($Cp^{0}$) was $114.19{\pm}20.78$ and $128.67{\pm}14.37{\mu}g/mL$, on day 1st and 3rd, respectively. The mean elimination half-life ($t_{1/2}ke$) was $1.00{\pm}0.28h$ on day 1st and $1.22{\pm}0.29h$ on day 3rd. Mean of area under concentration-time curve ($AUC_{0{\rightarrow}{\infty}}$) was $158.26{\pm}60.10$ and $159.70{\pm}22.74{\mu}g.h/mL$, on day 1st and 3rd respectively. The total body clearance ($Cl_{B}$) and volume of distribution at steady state (Vdss) on day 1st and 3rd were $Cl_{B}=0.07{\pm}0.02$ and $0.06{\pm}0.01L/h.kg$ and $Vdss=0.10{\pm}0.03$ and $0.11{\pm}0.05L/kg$, respectively. No-significant difference was noted in both drug-plasma concentration and pharmacokinetics-parameters, respectively. Amikacin concentration in plasma was found higher up-to 4 h and 6 h onward on down-ward trends favour to reduce toxicity. Which also support the pharmacokinetic-pharmacodynamic way of dosing of aminoglycosides and hence, amikacin may be administered 10 mg/kg intravenously daily to treat principally Gram-negative pathogens and limitedly Gram-positive-pathogens.

• The Korean Journal of Physiology and Pharmacology
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• 제14권2호
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• pp.77-81
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• 2010

Plasma cholesterol is increased in normal aging in both rodents and humans. This is associated with reduced elimination of cholesterol and decreased receptor-mediated clearance of plasma low-density lipoprotein (LDL) cholesterol. The aims of this study were: (1) to determine age-related changes in plasma lipid profiles, and (2) to determine the effect of fenofibrate, an activator of peroxisome proliferator activated receptor alpha (PPAR $\alpha$), on plasma lipid profiles in normal rats on a standard diet. Male Sprague-Dawley (SD) rats (n=15) were fed standard chow and water from 10 to 25 weeks of age. During that period, we measured daily food intake, body weight, fasting and random blood glucose levels, plasma total cholesterol (TC), triglycerides (TG), and free fatty acid (FFA) levels. At 20 weeks of age, all rats were randomly divided into two groups: a fenofibrate group (in which rats were gavaged with 300 mg/kg/day of fenofibrate) and a control group (gavaged with water). Fenofibrate treatment lasted 5 weeks. There were no significant changes in daily food intake, blood glucose, and plasma TG level with age. Body weight, plasma TC, and FFA levels were significantly increased with age. Fenofibrate significantly decreased plasma concentrations of TC and FFA, which had been increased with age. However, fenofibrate did not influence the plasma concentration of TG, which had not increased with age. These results suggest that fenofibrate might have a novel role in preventing age-related hypercholesterolemia in SD rats on a normal diet.

• 약학회지
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• 제34권4호
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• pp.238-243
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• 1990

Pharmacokinetic characteristics of recombinant human interleukin-2 (rH IL-2) wre studied in the rat. First, different doses of rH IL-2 ranging from 6,400 to 1,600,000 U/kg were injected intravenously and the effect of dose size on the pharmacokinetics was examined. There was no dose dependency in the pharmacokinetics of rHIL-2 in the dose range of 6,400-40,000 U/kg. But at the dose of 1,600,000 U/kg, there was a severe hemolysis throughout the experiment and the pharmacokinetic parameters such as Vdss and CLt were significantly increased compared to those obtained from lower doses. It also showed that this drug is hardly distributed to the peripheral tissues and hardly eliminated from the body, since the valume of distribution (Vdss) and total body clearance (CLt) were 45-75 ml/kg and 1-2 ml/min/kg, respectively. The Vdss is close to the actual plasma volume and the CLt is less than glomerular filtration rate (GFR). Therefore it seemed that rH IL-2 is distributed only in the plasma pool and hardly filtered in the kidney due to its very large molecular weight. Second, rH IL-2 was administered to the rat via several routes such as hepatic portal vein (PV), intraperitoneal (IP), peroral (PO) and intranasal (IN) routes. The bioavailabilities (BA) of PV, IP, PO and IN routes were 96.8, 4.9, 0 and 0.1%, respectively. The addition of some nasal absorption enhancers such as taurocholate, taurodeoxycholate, glycocholate and glycodeoxycholate did not increase the BA of intranasaly administered rH IL-2. The result is contrast to the effect of these bile salts on the nasal absorption of ${\alpha}-inteferon$. Considering it together with the pharmacokinetic parameters, very large molecular weight of rH IL-2 seemed again to be the cause to very poor membrane permeability.

• Preventive Nutrition and Food Science
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• 제2권4호
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• pp.338-347
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• 1997

Apo E polymorphism(e2, e3, e4) was among the first reported genetic polymorphism that explained part of the normal vairation in plasma cholesterol concentrations. Both alleles E2 and E4 are significantly more frequent in patients with mixed forms of hyperlipidemia and contribute on the observed differences in CHD risk among different populations. Effects of apo E polymorphism on the distribution of plasma lipid profiles were studied in 89 normolipidemic healthy females, aged 19 up to 22 years. The relative frequencies of E3/3 was 0.787, E3/2 was 0.101, E3/4 allele was 0.112 and no E2/2, E2/4 and E4/4 were found. Weight, height and %LBM were elevated in E2 than those in E3&E4. No differences in the blood pressure among apo E isomers were found, otherwise the pulsation was higher in E4 than that in the others. There were no differences in plasma total-, total DL-, HDL$_3$-, HDL$_2$ cholesterol, apo B-100 and apo A-I, However, phenotype means rank E3/2>E3/3>E3/4 in average TG levels(p<0.0001) significantly, and rank E3/4>E3/3>E3/2 in LDL cholesterol levels. These results were related to the correlation between atherogenic indiced (AI) such as LDL/HDL, (TC-HDL)/HDL, HDL$_3$/HDL$_2$. The ratio of HDL$_3$& HDL$_2$was significantly increased in E2 & E4 than that in E3(P=0.043). LCAT activity was not different between E2 and E3 but was highly increased in E4 (p<0.0001 among apo E isomers), but CETP was not different. Since the negative correlation between LCAT and CETP in apo E2(r=-0.491) was stronger than that in apo E3, E2 allele impacts the clearance of plasma apo E mediated lipoproteins. In conclusion firstly, E4 mediated alteration through LDL or E receptors results in lower TG or higher $\beta$-lipoprotein levels and E2 shows reciprocal effects of E4, respectively. Second, E4 allele was more atherogenic than E2 allele because the higher levels of AI such as HDL$_3$/HDL$_2$ were criticized.

• 한국임상약학회지
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• 제22권2호
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• pp.160-166
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• 2012

Purpose: The purpose of the present study was to investigate the pharmacokinetics of urea, a new potential diagnosis reagent of Helicobacter pylori infection. Methods: Considering the mechanism of urea breath test, we determined the excretion of urea in expired air after its oral administration in rats and beagle dogs at the dose of 2 mg/kg (including 50 mCi/mmol $^{14}C$-urea 50 ${\mu}Ci/kg$ for rats and 13.5 ${\mu}Ci/kg$ for dogs). Results: Urea was rapidly disappeared from the blood circulation by 1 hr after its i.v. bolus injection, followed by a slow disappearance by 24 hr. The half-lives at the distributive phase ($t_{1/2{\alpha}}$) and post-distributive phase ($t_{1/2{\beta}}$) were 2 min and 6 hr, respectively. The bioavailability of urea was 64.3% after its oral administration. The values of the volume of distribution ($V_{dss}$) and the total body clearance ($CL_t$) after the oral administration were compatible with those after i.v. administration. The recovery of urea in the bile was about 0.1% of the dose by 24 hr after its oral administration. Urea was extensively eliminated in the urine by 48 hr. The recovery ratios of urea in the urine and expired air were about 86.8% and 2.99% of the dose by 48 hr, respectively. Moreover, urea was mostly distributed from the blood circulation to the kidney, followed by being eliminated in the urine without metabolism. The concentration of urea in the kidney was 4.0 times higher than that of plasma at 40 min after its oral administration. Conclusions: These findings indicated that oral route appears to be available for the administration of urea. Orally administered urea, thus, was considered to be useful for the diagnosis of Helicobacter pylori infection.

• Biomolecules & Therapeutics
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• 제5권3호
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• pp.284-291
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• 1997

The pharmacokinetics and tissue distribution of DWP20367 (1-cyclopropyl-6-fluoro-8-chloro-7-(2, 7-diazabicyclo[3,3,0]tract-4-ene-7-yl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid), a novel fluoroquinolone, were examined in rats and beagle dogs after a single intravenous and oral administration. Analysis of DWP20367 in plasma, tissue, and urine was determined by both HPLC and microbiological assay (bioassay). The plasma concentration-time curves of the drug in rats and beagle dogs were biexponentially declined. The terminal half-life (t$_{1}$2$\beta$/) of the drug in rats was about 60.1 $\pm$7.3 min (i.v.) and 61.3 $\pm$ 12.4 min (p.o.) in bioassay, and 86.3 $\pm$19.8 min (i.v.) and 50.9$\pm$ 14.9 min (p.o.) in HPLC. In beagle dogs, half-life of the drug determined by bioassay was about 121.8$\pm$6.2 min (i.v.) and 111.0$\pm$7.6 min (p.o.). The volume of distribution at steady-state (Vd$_{ss}$ ) was 243.8$\pm$74.1 ml/kg (bioassay) and 339.2$\pm$84.3 ml/kg (HPLC) in rats, and 1587.5 $\pm$536.9 ml/kg (bioassay) in beagle dogs. The total body clearance (Cl$_{t}$) of DWP20367 was 3.4 $\pm$ 0.4 ml/min/kg (bioassay) and 2.4$\pm$0.4 ml/min/kg (HPLC) in rats, and 12.3$\pm$ 1.0 ml/min/kg (bioassay) in beagle dogs, respectively. The extent of bioavailability after oral administration was 89.1%(bioassay) and 79.9% (HPLC) in rats, and 78.7% (bioassay) in beagle dogs. Urinary recovery (24-h) assayed by bioassay was 0.7% (p.o.) and 1.2% (i.v.) in rats, and 0.8% (p.o.) and 1.0% (i.v.) in beagle dogs. In rats, 24-h fecal recovery determined by bioassay was 11.2% (p.o.) and 0.1% (i.v.). Rat and human serum protein binding ratios at 2$\mu$g/ml were about 90~91%. This drug determined by bioassay was also distributed by the order of liver, kidney, lung, heart, spleen and muscle 30 min after oral administration.on.

• 약학회지
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• 제41권3호
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• pp.328-334
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• 1997

Pharmacokinetics of DWP401, a recombinant human epidermal growth factor (rhEGF), was studied using radioimmunoassay (RIA) and $^{125}I$-DWP401 in rats. When DWP401 was adm inistered i.v. at doses of 50 and 500 mcg/kg, the plasma DWP401 disappeared biiexponentially with terminal half life of 4.7 and 92.8 min. The $C_{max}$ and $T_{max}$ after s.c. administration of ti at doses of 50 and 500 ${\mu}g$/kg were determined to be 23.6 and 17.5 ng/ml at 50 ${\mu}g$/kg, and 261.4 ng/ml and 36.8 min, respectively. Both the total urinary and biliary recoveries of intact DWP401 2343 very low (<0.4%), probably due to its extensive degradation in the body. the concentration ratio of DWP401 between the organ and plasma decreased especially in the liver and kidney as the dose and time after the dose increased. For example, the liver/plasma and kidney/plasma concentration ratio of DWP401 at 2.5 min after i.v. doses of 50 ${\mu}g$/kg were comparable and much larger than unity. But, the ratio at 2.5 min after i.v. doses of 500${\mu}g$/kg was much larger in the kidney that in than in the liver. These results suggest that the systemic administration of DWP401 might be subject to rapid and extensive clearance from circulation within several hour after main distrbution to liver and kidney.

• Journal of Pharmaceutical Investigation
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• 제40권2호
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• pp.101-107
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• 2010

A rapid and sensitive reversed-phase high performance liquid chromatography (HPLC) method was developed for the determination of N-(-4-Chlorophenyl)-6-hydroxy-7-methoxy-2-chromanecarboxamide (KAL-1120), a novel anti-inflammation agent, in the rat plasma. The method was applied to analyze the compound in the biological fluids such as bile, urine and tissue homogenates. After liquid-liquid extraction, the compound was analyzed on an HPLC system with ultraviolet detection at 275 nm. HPLC was carried out using reversed-phase isocratic elution with a $C_{18}$ column, a mobile phase of a mixture of acetonitril (40 v/v%) at a flow rate of 1.0 mL/min. The chromatograms showed good resolution and sensitivity and no interference of plasma. The calibration curve for the drug in plasma was linear over the concentration range of 0.05-50 ${\mu}g$/mL. The intra- and inter-day assay accuracies of this method ranged from 0.06% to 9.33% of normal values and the precision did not exceed 6.28% of relative standard deviation. The plasma concentration of KAL-1120 decreased to below the quantifiable limit at 1.5 hr after the i.v. bolus administration of 2-10 mg/kg to rats ($t_{1/2,({\alpha})}$ and $t_{1/2,({\beta})$ of 2.15 and 26.7 min at a dose of 2 mg/kg, 3.91 and 33.0 min at a dose of 10 mg/kg, respectively). The steady-state volume of distribution ($V_{dss}$) and the total body clearance ($CL_t$) were not significantly altered in rats given doses from 2 to 10 mg/kg. Of the various tissues tested, KAL-1120 was mainly distributed in the lung and heart after i.v. bolus administration. KAL-1120 was detected in the bile by 30 min after its i.v. bolus administration. However, the concentration in the urine after i.v. bolus administration became too low to measure, suggesting that KAL-1120 is mostly excreted in the bile. In conclusion, this analytical method was suitable for the preclinical pharmacokinetic studies of KAL-1120 in rats.

• 한국임상약학회지
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• 제12권2호
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• pp.91-95
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• 2002

The pharmacokinetics of intravenous paclitaxel (1 mg/kg) were investigated in rabbits with renal failure induced by folic acid. The area under the plasma concentration-time curve from time zero to time infinity (AUC) of paclitaxel was significantly (p<0.05) greater in rabbits with severe renal failure induced by folic acid $(1030\pm382)$ compared to that in rabbits with in moderate renal failure induced by folic acid $(780\pm209\;ng/ml{\cdot}hr)$. The apparent volume of distribution (Vd) $(0.008\pm0.002\;L/kg)$ and the elimination rate constant $(\beta)\;(0.09\pm0.025\;hr^{-1})$ of paclitaxel in rabbits with severe renal failure were significantly (p<0.05) smaller and slower respectively than those of control rabbits $(0.016\pm0.004\;L/kg,\;0.12\pm0.03\;hr^{-1})$, but not significantly different compared with that in rabbits with moderate renal failure $(0.010\pm0.003\;L/kg,\;0.10\pm0.026\;hr^{-1})$. total body clearance (CL) of paclitaxel in rabbits with severe renal failure $(0.97\pm0.183\;L/hr/kg)$ was significantly (p<0.05) slower than that in control rabbits $(1.68\pm0.440\;L/hr/kg)$, but not significantly different compared with that in rabbits with in moderate renal failure $(1.28\pm0.311\;L/hr/kg)$. The terminal half-life ($t_{1/2}$) of paclitaxel in rabbits with severe renal failure $(7.46\pm2.16\;hr)$ was significantly (p<0.05) longer than that in control rabbits $(5.75\pm1.44\;hr)$, but not significantly different compared to that in rabbits with moderate renal failure rabbits $(6.67\pm1.76\;hr)$. The above data could be at least partly decrease in due to paclitaxel excretion in rabbits with renal failure, since $7-15\%$ of interavenous paclitaxel was excreted via kidney as unchanged forms plus its metablites.