کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10909565 | 1087920 | 2005 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
A phase I and pharmacologic study of idarubicin, cytarabine, etoposide, and the multidrug resistance protein (MDR1/Pgp) inhibitor PSC-833 in patients with refractory leukemia
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کلمات کلیدی
AMLCML-BCSWOGCmaxMDR1MUGADLTMTDAkaike's information criteriaPGPAICANCIRBECoGMDSAUC - AUCP-glycoprotein - P-گلیکوپروتئینAra-C - آرا- CInteraction - اثر متقابلAbsolute neutrophil count - تعداد نوتروفیل مطلقMaximum tolerated dose - حداکثر دوز قابل تحملmaximum plasma concentration - حداکثر غلظت پلاسماCNS - دستگاه عصبی مرکزیdose limiting toxicity - دوز محدودیت سمیتmyelodysplastic syndrome - سندرم میلودیسپلاستیکcytarabine - سیتارابینcentral nervous system - سیستم عصبی مرکزیPharmacokinetics - فارماکوکینتیکacute myeloid leukemia - لوسمی حاد میلوئیدی یا به اختصار AMLAcute lymphoblastic leukemia - لوسمی لنفوبلاستیک حادchronic myelogenous leukemia in blast crisis - لوسمی مزمن میلوئیدی در بحران انفجارMultidrug resistance - مقاومت چند داروییALL - همهinstitutional review board - هیئت بررسی نظارتPartial response - پاسخ جزئیcomplete response - پاسخ کاملTransport proteins - پروتئین حمل و نقلHPLC - کروماتوگرافی مایعی کاراhigh-performance liquid chromatography - کروماتوگرافی مایعی کاراSouthwest Oncology Group - گروه آنوکولوژی جنوب غربی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
This study was conducted to define the maximum tolerated dose (MTD), dose limiting toxicity (DLT), and pharmacokinetics of idarubicin when administered with and without the P-glycoprotein inhibitor PSC-833 in combination with cytarabine, and etoposide. Fifteen patients with relapsed and refractory acute leukemia were enrolled and received cytarabine as a 7-day continuous infusion, with etoposide and idarubicin administered for any three consecutive days during the cytarabine infusion. Two hours prior to the second dose of idarubicin, PSC-833 administration was initiated. The pharmacokinetics of idarubicin alone and with PSC-833 was assessed at three idarubicin dose levels (6, 8 and 10 mg/m2). The MTD of idarubicin in this combination was 8 mg/(m2 day) with a DLT of oral mucositis. The complete remission rate (on an intent-to-treat basis) for this regimen was 33%, with a median duration of 6 months. The clearance of idarubicin was 140 ± 200 and 181 ± 94.3 l/h for idarubicin alone and with PSC-833, respectively. The volume of distribution of the central compartment was 423 ± 443 and 337 ± 394 l for idarubicin alone and in combination with PSC-833, respectively. This combination including PSC-833 was well tolerated. Although a pharmacokinetic interaction might have been expected, PSC-833 did not significantly alter the disposition of idarubicin.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Leukemia Research - Volume 29, Issue 3, March 2005, Pages 263-271
Journal: Leukemia Research - Volume 29, Issue 3, March 2005, Pages 263-271
نویسندگان
Kenneth S. Bauer, Judith E. Karp, Tushar S. Garimella, Suhlan Wu, Ming Tan, Douglas D. Ross,