• Clinical and Experimental Pediatrics
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• v.52 no.5
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• pp.581-587
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• 2009

Purpose : To evaluate the correlation between serum methotrexate (MTX) peak levels and clinical outcome of osteosarcoma, as well as to determine the correlation of these levels with the histologic response and event-free survival (EFS). Methods : To maintain the homogeneity of the study population, we selected 52 patients with localized extremity osteosarcoma who had received two cycles of neoadjuvant chemotherapy consisting of high-dose (HD) MTX ($12g/m^2$), cisplatin ($100mg/m^2$), and doxorubicin ($60mg/m^2$). Results : Totally, 204 courses of HD MTX were administered. The serial MTX levels ($mean{\pm}SE$) at 4 h (peak), 24 h, 48 h, and 72 h were $1292.14{\pm}12.83{\mu}m$, $9.29{\pm}3.89{\mu}m$, $1.73{\pm}1.37{\mu}m$, and $0.58{\pm}0.44{\mu}m$, respectively. The peak MTX serum level was $1292.14{\pm}12.83{\mu}m$. Neither the continuous average MTX peak level nor the dichotomized MTX peak level was related to the histologic response. However, the patients with a high 24-h MTX level ($3.4{\mu}m$) had a poor histologic response (P=0.044). An inverse relationship was observed between MTX levels and survival: the EFS was better in the patients with a mean MTX peak level of less than $1,400{\mu}m$ (P=0.002) and mean 24-h MTX level of less than $3.4{\mu}m$ (P=0.011). Conclusion : The inverse correlation between the MTX level and the outcome is an unexpected finding. Further study on the pharmacokinetics of MTX is required to substantiate our findings and elucidate the mechanism involved.

• Pediatric Infection and Vaccine
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• v.18 no.2
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• pp.109-116
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• 2011

Purpose : Pneumococcus is one of the most important causes of invasive infection through the childhood period. In January 2008, the Clinical and Laboratory Standards Institute (CLSI) published revised penicillin breakpoints for Streptococcus pneumoniae and penicillin susceptibility rates of S. pneumoniae increased in Korea. This study was performed to determine the probability of oral amoxicillin for the empirical treatment achieving bactericidal exposure against pneumococcus using pharmacodynamics model. Methods : Twenty-three isolates of pneumococci were subjected to determine minimum inhibitory concentration (MIC) for ${\beta}$-lactams and macrolide. For the ${\beta}$-lactams, exposure of fT >MIC (time that free drug concentrations remain above the MIC) for 50% of the administration interval have determined the probability of target attainment (PTA), and regimens that had a PTA >90% were considered optimal. An analysis was performed by applying MIC of 23 isolates to a 5000-patient Monte Carlo simulation model. Results : Among 23 isolates from healthy children, 7 (30.4%) isolates were MIC ${\leq}$1.0 ${\mu}g$/mL and 19 (82.6%) were MIC ${\leq}$2 ${\mu}g$/mL for amoxicillin. Amoxicillin 40 mg/kg/day achieved PTA >90% at MIC ${\leq}$1.0 ${\mu}g$/mL but PTA decreased to 52% at MIC 2 ${\mu}g$/mL, whereas amoxicillin 90 mg/kg/day can predict 97% of PTA at MIC 2 ${\mu}g$/mL. Overall, oral amoxicillin 90 mg/ kg/day for the empirical treatment against pneumococcus can expect more successful response in Korean children. Conclusion : Considering the resistantce pattern of pneumococci in Korean children, we estimate that oral amoxicillin 90 mg/kg/day will provide a pharmacodynamic advantage for the empirical treatment against pneumococcus. And low dose amoxicillin or macrolide are expected to have higher chance of treatment failure than high dose oral amoxicillin.