Reference

Plasma and cerebrospinal fluid population pharmacokinetics of temozolomide in malignant glioma patients

Plasma and cerebrospinal fluid population pharmacokinetics of temozolomide in malignant glioma patients. Ostermann, Sandrine; Csajka, Chantal; Buclin, Thierry; Leyvraz, Serge; Lejeune, Ferdy; Decosterd, Laurent A.; Stupp, Roger (Multidisciplinary Oncology Center, Centre Hospitalier Universitaire Vaudois, Lausanne, Switz.Several substances are used for example 85622-93-1 which is its cas registry number.). Clinical Cancer Research, 10(11), 3728-3736 (English) 2004 American Association for Cancer Research. CODEN: CCREF4. ISSN: 1078-0432. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Scarce information is available on the brain penetration of temozolomide (TMZ), although this novel methylating agent is mainly used for the treatment of malignant brain tumors. The purpose was to assess TMZ pharmacokinetics in plasma and cerebrospinal fluid (CSF) along with its inter-individual variability, to characterize covariates and to explore relationships between systemic or cerebral drug exposure and clin. outcomes. TMZ levels were measured by high-performance liq. chromatog. in plasma and CSF samples from 35 patients with newly diagnosed or recurrent malignant gliomas. The population pharmacokinetic anal. was performed with nonlinear mixed-effect modeling software. Drug exposure, defined by the area under the concn.-time curve (AUC) in plasma and CSF, was estd. for each patient and correlated with toxicity, survival, and progression-free survival. A three-compartment model with first-order absorption and transfer rates between plasma and CSF described the data appropriately. Oral clearance was 10 L/h; vol. of distribution (VD), 30.3 L; absorption const. rate, 5.8 h-1; elimination half-time, 2.1 h; transfer rate from plasma to CSF (Kplasma CSF), 7.2 x 10-4h-1 and the backwards rate, 0.76 h-1. Body surface area significantly influenced both clearance and VD, and clearance was sex dependent. The AUCCSF corresponded to 20% of the AUCplasma. A trend toward an increased Kplasma CSF of 15% was obsd. in case of concomitant radiochemotherapy. No significant correlations between AUC in plasma or CSF and toxicity, survival, or progression-free survival were apparent after deduction of dose-effect. This is the first human pharmacokinetic study on TMZ to quantify CSF penetration. The AUCCSF/AUCplasma ratio was 20%. Systemic or cerebral exposures are not better predictors than the cumulative dose alone for both efficacy and safety. .

Antitumor sustained-release injection containing clofarabine and its synergistic agents

All Rights Reserved. Antitumor sustained-release injection containing clofarabine and its synergistic agents. Kong, Qingxin (Jinan Kangquan Pharmaceutical Science and Technology Co., Ltd., Peop. Rep. China). Faming Zhuanli Shenqing Gongkai Shuomingshu CN 1875940 A 13 Dec 2006, 27pp. (Chinese). (People's Republic of China). CODEN: CNXXEV. APPLICATION: CN 2010-200705 18 Jul 2006. DOCUMENT TYPE: Patent CA Section: 63 (Pharmaceuticals) Section cross-reference(s): 1 The sustained-release injection is comprised of (A) sustained-release microsphere comprising effective constituent of clofarabine and its synergistic agents from phosphoinositide-3-kinase inhibitors and/or tetrazine compds. 0.5-60, sustained-release adjuvant 40-99% and suspending agent 0.0-30.0%; and (B) solvent. The phosphoinositide-3-kinase inhibitors are selected from camptothecin, podophyllotoxin, lurtotecan, or the mixt. thereof. The tetrazine compds. are selected from procarbazine, mitozolomide, 4-carboxy temozolomide, temozolomide, or the mixt. thereof. The sustained-release adjuvant is polylactic acid, polyglycolic acid-hydroxy acetic acid copolymer, polifeprosan, racemic polylactic acid, etc., or the mixt. 85622-93-1 and 9003-01-4 are just another two chemicals used in this study. thereof. The suspending agent is one of (sodium) CM-cellulose, mannitol, sorbitol, etc. .