• Clinical and Experimental Pediatrics
• /
• v.51 no.10
• /
• pp.1038-1041
• /
• 2008

Aminoglycosides are frequently used antibiotics in children. The multiple daily dosing (MDD) in infants and children is twice or three times daily depending on age. Recent studies in adults have shown that once daily dosing (ODD) maximizes the bactericidal activity and might minimize the toxicity of antibiotics. So, I reviewed many studies about efficacy, toxicity and cost effectiveness of ODD of aminoglycosides in children. Most studies suggest that ODD compared with MDD of aminoglycosides is theoretically more efficacious and has no higher toxicity in infants and children. But, the total number of patients included in the studies is not large. Multi-center, controlled prospective studies are required in larger numbers of infants and children to determine the efficacy and safety of the ODD regimen in children before ODD of aminoglycosides can be recommended for routine use.

• Clinical and Experimental Pediatrics
• /
• v.53 no.12
• /
• pp.1000-1005
• /
• 2010

Purpose: This study aimed to determine the optimal initial vancomycin dose to achieve appropriate trough levels in pediatric patients. Methods: We analyzed clinical data for 309 children treated with intravenous vancomycin between 2004 and 2009 at 2 different hospitals in South Korea. The patients were 1-16 years old and exhibited normal renal function. Patient data, including reason for treatment and initial dosing regimen, were reviewed. Two subgroups were identified and compared according to initial vancomycin dose: 40 (35-45) mg/kg/day and 60 (55-65) mg/kg/day. Trough levels were obtained at steady state after at least 4 doses of vancomycin. Results: Patients who received vancomycin had post-operation or wound-related infections (37.2%), localized infection (12.9%), catheter-related infections (9.4%), meningitis (8.7%), or endocarditis (6.8%). Pathogens were confirmed in 79 cases: 28 cases of methicillin-resistant $Staphylococcus$ $epidermidis$ (35.4%) and 25 of methicillin-resistant $Staphylococcus$ $aureus$ (31.6%). Out of the 309 patients, 201 (65%) received vancomycin at 40 mg/kg/day and 108 (35%) at 60 mg/kg/day. Average trough concentrations were significantly different between the groups ($P$<0.001). Trough levels over 10 mg/L were less likely to be achieved in the 40 mg/kg/day group (14%) than in the 60 mg/kg/day group (49%) ($P$<0.001). There were no differences in renal function deterioration between the groups. Conclusion: A common vancomycin dosing regimen, 40 mg/kg/day, was not high enough to achieve trough levels of over 10 mg/L in pediatric patients. Careful drug monitoring must be performed, and increasing initial dose of vancomycin should be considered in pediatric patients.

• Journal of Pharmaceutical Investigation
• /
• v.38 no.3
• /
• pp.151-155
• /
• 2008

Circadian variations of acebutolol and its main metabolite, diacetolol pharmacokinetics were studied after a single oral administration of acebutolol (10 mg/kg) to eight rabbits at 10 : 00 AM (in the morning) and 10 : 00 PM (at night). The plasma concentration profiles of acebutolol were significantly different (P<0.05) between 10 : 00 AM and 22 : 00 PM, suggesting circadian variations of pharmacokinetic behaviors. A significant circadian rhythm of pharmacokinetic parameters was noted in rabbits, showing higher total body clearance (CL/F), and lower the area under the plasma concentration-time curves (AUC) of acebutolol than that at night. The half-life ($t_{1/2}$) of acebutolol and diacetolol were also significantly shorter in the morning than at night (P<0.05). Metabolite-parent AUC ratio at night significantly decreased compared to in the morning, implying that night time could inhibit acebutolol metabolism than in the morning. From this study there was an administration-time difference of acebutolol pharmacokinetics in the rabbits. The optimized dosing regimen of acebutolol can be decided by considering circadian rhythm so that the effective therapies are established for patients.

• Korean Journal of Clinical Pharmacy
• /
• v.6 no.2
• /
• pp.7-13
• /
• 1996

The purposes of this study were to define the pharmacokinetic parameters of vancomycin in Korean neonates, to evaluate current neonatal vancomycin dosing guideline being used in a teaching hospital, and to develop the optimal vancomycin dosing guideline. The evaluation of 35 sets of peak and trough concentrations drawn on current dosing regimen showed that $29\%$ of peak concentrations and $46\%$ of though concentrations were within therapeutic range. Otherwise, pharmacokinetic parameters, based on 62 sets of peak and trough serum concentrations obtained from 39 neonates, showed that mean vancomycin clearance (CL), volume of distribution (Vd), and terminal elimination half-life were $0.13\pm0.08\;L/hr,\;0.94\pm0.48\;L,\;and\;5.6\pm2.13$ hours, respectively. Volume of distribution (Vd) normalized for body weight remained constant throughout PCA range, whereas the absolute CL (r=0.74) and normalized CL (r=0.36) showed high correlation with PCA. Also, the normalized CL showed a strong inverse correlation (r=-0.55) with serum creatinine concentrations (SrCr). Based on the high correlation among PCA serum creatinine concentration, CL, and the daily dosage requirements, the following dosing guideline for vancomycin in neonates was suggested: 10 mg/kg $12{\sim}18$ hourly for < 30 weeks PCA and < 0.6 mg/dl SrCr; 10 mg/kg 18 hourly for < 30 weeks PCA and $0.6{\sim}1.2$ mg/dl SrCr; 10 mg/kg 8 hourly for $30\sim44$ weeks PCA and < 0.6 mg/dl SrCr; 10 mg/kg 12 hourly for $30\sim44$ weeks PCA and $0.6{\sim}1.2$ mg/dl SrCr.

• YAKHAK HOEJI
• /
• v.45 no.2
• /
• pp.153-160
• /
• 2001

This research developed an intravenous (IV) vancomycin dosing nomogram based on the clinical pharmacokinetic data of Korean adult patients. Total 99 pairs of steady-state peak and trough serum concentrations of vancomycin were obtained from 73 adult patients in a tertiary general hospital. Serum vancomycin concentrations were determined to assess the appropriateness of initial vancomycin dosing. Only 47.2% of the cases were within therapeutic range. To characterize the clinical pharmacokinetics (PK) of vancomycin, PK parameters including elimination rate constant ( $K_{e}$) half-life( $T_{1}$2/), clearance (C $l_{van}$), volume of distribution ( $V_{d}$) were calculated by using one-compartment, first order pharmacokinetic equations. PK parameters were evaluated based on the differences of patients'renal function and age. Regression analysis showed a significant correlation between C $l_{van}$ and $C_{cr}$ (C $l_{van}$ = -1.89+0.914 $C_{cr}$ , r=0.763) and between $K_{e}$ and $C_{cr}$ , ( $K_{e}$=-0.0037+0.00139 $C_{cr}$ =0.724). The relationship between $K_{e}$ and $C_{cr}$ , and the mean $V_{d}$ were utilized for developing the nomogram to individualize the initial dosing regimen of vancomycin for the patients with various degrees of renal functions. The nomogram may be used as an efficient tool to determine safe and effective doses of vancomycin for the Korean adult patients.nts.nts.nts.s.nts.

• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.4
• /
• pp.1903-1907
• /
• 2016

Background: Studies of effects of IL-1 polymorphisms, CYP2C19 genotype together with antibiotic resistance for H. pylori eradication are rare worldwide. The present study was designed to evaluate efficacy of 10-day sequential therapy (SQT) and 14-day standard triple therapy (STT) with four- times-daily dosing of amoxicillin for H. pylori eradication related to these important host and bacterial factors in Thailand. Materials and Methods: This prospective randomized study was performed during March 2015 to January 2016. H. pylori infected gastritis patients were randomized to receive 10-day sequential therapy and 14-day standard triple therapy. CYP2C19 genotyping, IL1 polymorphism (IL-1B and IL-1RN genotypes) and antibiotic susceptibility tests were performed in all patients. 13C-UBT was conducted to confirm H. pylori eradication at least 4 weeks after treatment. Results: A total of 100 patients (33 males and 67 females, mean age=51.1 years) were enrolled. Eradication rate by PP analysis was 97.9% (47/48) with the 10-day SQT regimen and 87.8% (43/49) with 14-day STT regimen (97.9% vs 87.8%; p-value=0.053). Antibiotic susceptibility testing demonstrated 45% resistance to metronidazole, 14.8% to clarithromycin, and 24.1% to levofloxacin. CYP2C19 genotyping revealed 44.9% RM, 49% IM and 6.1% PM. IL-1B and IL-1RN genotypes were demonstrated as 21.4% for CC, 48.1% for TC, 36.8% for TT, 72.7% for 1/1, and 21.2% for 1/2 genotypes, respectively. The 10-day SQT regimen provided 100% eradication in patients with clarithromycin or dual clarithromycin and levofloxacin H. pylori resistant strains. Moreover, the 10-day SQT regimen resulted in a 100% eradication rate in all patients with CYP2C19 genotype RM and almost type of IL-1B (TC and TT) and IL1-RN genotypes ( 1/2 and other). Conclusions: Treatment with 10-day sequential therapy is highly effective for H. pylori eradication regardless of the effects of clarithromycin resistance, dual clarithromycin and levofloxacin resistance, CYP2C19 genotype, IL-1B and IL1-RN genetic polymorphisms and can be used as effective first line therapy in Thailand.

• Korean Journal of Clinical Pharmacy
• /
• v.11 no.2
• /
• pp.57-61
• /
• 2001

The effect of circadian rhythm on the pharmacokinetics of acebutolol was studied in rabbits administered intravenous 5 mg/kg dose of acebutolol at 09:00 in the morning (a.m) and 22:00 in the evening (p.m). A significant effect of circadian rhythm of pbarmacokinetic parameters as a function of time of day was noted in rabbits, showing lower total body clearance (CLt), higher plasma concentration and the area under the plasma concentration time curve (AUC) when acebutolol was given in the evening. The plasma concentration of acebutolol was increased significantly (p<0.05) at 12-24 hr after dosing in the evening. The AUC was greater in the evening $(111\%)$ than that in the morning and $CL_t$, was higher when acebutolol was given in the morning ($1.12\pm0.24$ ml/hr) versus in the evening ($1.01\pm0.22$ ml/hr), but those were not significant. Therefore, It is reasonable to consider individual circadian rhythm for effective dosage regimen of acebutolol in clinical chronotherapeutics.

• Clinical and Experimental Pediatrics
• /
• v.57 no.3
• /
• pp.153-156
• /
• 2014

Toxic epidermal necrolysis is an unpredictable and severe adverse drug reaction. In toxic epidermal necrolysis, epidermal damage appears to result from keratinocyte apoptosis. This condition is triggered by many factors, principally drugs such as antiepileptic medications, antibiotics (particularly sulfonamide), nonsteroidal anti-inflammatory drugs, allopurinol, and nevirapine. Lamotrigine has been reported potentially cause serious cutaneous reactions, and concomitant use of valproic acid with lamotrigine significantly increases this risk. We describe a case of an 11-year-old girl with tic and major depressive disorders who developed toxic epidermal necrolysis after treatment with lamotrigine, and who was diagnosed both clinically and pathologically. Children are more susceptible to lamotrigine-induced rash than adults, and risk of serious rash can be lessened by strict adherence to dosing guidelines. Unfortunately, in our case, the patient was administered a higher dose than the required regimen. Therefore, clinicians should strictly adhere to the dose regimen when using lamotrigine, especially in children.

• YAKHAK HOEJI
• /
• v.44 no.1
• /
• pp.16-21
• /
• 2000

Peptic ulcer is involved with Helicobacter pylori infection and antibiotic regimens are primary treatments. An optimal therapeutic regimen for eradication of Helicobacter pylori remains uncertain due to variable efficacy. The objectives of this study were to evaluate the efficacy of omeprazole based antibiotic regimens in bacterial eradication, healing of peptic ulcer and to identify factors affecting efficacy. Seventy-seven patients were enrolled in the prospective, open-trial from November 1997 to Setember 1998. H. pylori infection was identified with endoscopy, H. pylori stain and rapid urease test. The first group (OAC7) received omeprazole 20 mg twice daily for 4 weeks which were the same schedule for all, amoxicillin and clarithromycin 500 mg three times daily for 1 week; the second group (OAC14), for 2 weeks on the same regimen as the first; and the last group (OACD) has taken bismuth in addition to the OAC7 regimen for 1 week. Eradication of H. pylori and healing of peptic ulcer were evaluated with endoscopy and tests for H. pylori before and after treatments. There were no significant differences in eradication rates; 77% in OAC7, 76% in OAC14, 81% in OACD (p=0.935) and healing rates; 82% in OAC7, 71% in OAC14, 95% in OACD (p=0.179), respectively. Compliance had an relationship with eradication rates significantly among regimens (p=0.049). Twenty three cases (29%) complained of the minor side effects. In conclusion, OAC7 was better in convenience of dosing schedule and showed fewer side effects with shorter duration and lower cost while There were no significant differences in efficacy among regimens.

• Korean Journal of Clinical Pharmacy
• /
• v.2 no.1
• /
• pp.23-28
• /
• 1992

This study was attempted to investigate the pharmacokinetics of theophylline(4mg/kg) in the rabbits of carbon tetrachloride induced hepatic Cailure, The plasma concentration and relative bioavailability of theophylline were increased significantly in hepatic railure rabbits compared with those of normal rabbits. There was significant relationship between SGOT value and bioavailability parameters of theophylline. From the results of this experiments, dosage regimen of theophylline is considered to be adjusted in dose size and dosing interval using SGOT values.