Morikawa N, Mori T, Kawashima H, Takeyama M, Hori S
Department of Clinical Pharmacy, Oita Medical University, Japan.
Ann Pharmacother. 1998 Oct;32(10):1008-12. doi: 10.1345/aph.17362.
To examine the pharmacokinetics of anticancer drugs in the cerebrospinal fluid (CSF) during chemotherapy by the lumbar-ventricular (LV) and ventricular-lumbar (VL) routes.
A 69-year-old Japanese woman with disseminated glioblastoma received two LV and four VL courses of CSF perfusion chemotherapy with methotrexate, nimustine, and cytarabine hydrochloride. Samples of CSF from the ventricles and lumbar spinal canal were obtained via Ommaya reservoirs during one LV and one VL course. Drug concentrations in the CSF were measured by fluorescence polarization immunoassay or HPLC.
During LV CSF perfusion, the highest CSF drug concentrations in both the ventricles and the lumbar spinal canal were observed at the end of perfusion. During treatment, the concentrations of all three drugs in the lumbar spinal canal were higher than those in the ventricles. The CSF AUC of methotrexate in the ventricles was 16.1% of that in the lumbar spinal canal. During VL CSF perfusion, the highest drug concentrations were also observed at the end of perfusion. The drug concentrations in the lumbar spinal canal were initially lower than those in the ventricles. However, the concentrations of methotrexate and cytarabine in the lumbar spinal canal exceeded those in the ventricles 3 hours after perfusion. The AUC of methotrexate in the lumbar spinal canal was 174.9% of that in the ventricles.
The pharmacokinetics of anticancer drugs in ventricular CSF differ from those in lumbar CSF during LV and VL perfusion chemotherapy.
通过腰-脑室（LV）和脑室-腰（VL）途径，研究化疗期间脑脊液（CSF）中抗癌药物的药代动力学。
一名69岁的日本女性，患有弥漫性胶质母细胞瘤，接受了两疗程的LV和四疗程的VL脑脊液灌注化疗，使用甲氨蝶呤、尼莫司汀和盐酸阿糖胞苷。在一个LV疗程和一个VL疗程中，通过奥马亚贮液器采集脑室和腰段椎管的脑脊液样本。脑脊液中的药物浓度通过荧光偏振免疫测定法或高效液相色谱法测量。
在LV脑脊液灌注期间，脑室和腰段椎管中的脑脊液药物浓度在灌注结束时最高。治疗期间，腰段椎管中所有三种药物的浓度均高于脑室中的浓度。脑室中甲氨蝶呤的脑脊液药时曲线下面积（AUC）是腰段椎管中的16.1%。在VL脑脊液灌注期间，药物浓度在灌注结束时也最高。腰段椎管中的药物浓度最初低于脑室中的浓度。然而，灌注3小时后，腰段椎管中甲氨蝶呤和阿糖胞苷的浓度超过了脑室中的浓度。腰段椎管中甲氨蝶呤的AUC是脑室中的174.9%。
在LV和VL灌注化疗期间，脑室脑脊液中抗癌药物的药代动力学与腰段脑脊液中的不同。
