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Plasma Levels of Oral Methotrexate in Children Receiving Maintenance Chemotherapy for Acute Lymphocytic Leukemia

Journal of the Korean Pediatric Society 1993;36(7):936-943.
Published online July 15, 1993.
Plasma Levels of Oral Methotrexate in Children Receiving Maintenance Chemotherapy for Acute Lymphocytic Leukemia
Soo Kwan Lee, Kih Yeon Song, Young Hee Hwang, Young Hwan Lee, Jeong Ok Hah, Chun Dong Kim
Department of Pediatrics, College of Medicine, Yeungnam University, Taegu, Korea
급성 임파구성 백혈병 환아에서 경구용 Methotrexate 투여후의 혈중 농도
이수관, 송기연, 황영희, 이영환, 하정옥, 김춘동
영남대학교 의과대학 소아과학교실
Abstract
This study was conducted to investigate plasma levels of oral methotrexate in rabbits and children receiving maintenance chemotherapy for acute lymphocytic leukemia. Eight New Zealand white rabbits, weighing 2kg in body weight, were divided into 3 groups and 5mg of methotrexate from 3 different manufactorying company was administered to the each group rabbits via nasogastric tube. Time to peak concentration ranged from 30 minutes to 3 hours (mean 1.2±0.9 hour) and the peak plasma concentration ranged from 0.08μM to 0.21μM (mean 0.14±0.05μM) and area under the plasma concentration-time curve ranged from 0.6μM,hr to 1.66μM,hr(mean 1.06 ±0.36μM,hr). There were no statistically significant difference in AUC of methotrexate in 3 groups, but interindividual variability in plasma levels of methotrexate was noted. Twelve patients with ALL who were receiving maintenance chemotherapy at pediatric department of Yeungnam University Hospital from August, 1988 to August, 1991 were studied. Plasma levels of oral methotrexate were monitored following an oral dose of 3.3mg~10mg/㎡ which was modified from recommended dose of 10mg/㎡ due to hepatotoxicity or myelosuppression. Time to peak concentration ranged from 30 minutes to 2 hours (mean 1.2±0.4hour) and the peak plasma concentration ranged from 0.34μM to 0.8μM (mean 0.58±0.18μM ). The area under the plasma concentration-time curve ranged from 1.25μM,hr to 3.79μM,hr (mean 2.71±0.84μM,hr ) while standard area under to plasma concentration-time curve ranged from 0.13μM,hr /mg/㎡ to 0.54μM,hr/mg/㎡ (mean 0.4±0.15μM,hr/mg/㎡). Interindividual variability in plasma levels following an oral dose of methotrexate was noted. Peak plasma concentrations of study patients were all less than 1μM which is necessary for antileukemic effect of methotrexate in vitro. It seems to be necessary to increase the dose of methotrexate for all study patients, however optimal dose increment of methotrexate avoiding hepatotoxicity and myelosuppression need to be investigated further and measurement of plasma level of methotrexate is recommended when dose modification of methotrexate is made.
Key Words: Oral Methotrexate, Pharmacology, Acute lymphocytic leukemia


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