Infusing drug solution directly into brain fluid

Abstract

A method of treating a subject which may be a human suffering from epilepsy which may be a form of epilepsy resistant to treatment and particular patients which are resistant to treatment with oral medication. The method involves positioning a catheter device in the subject's brain and infusing a liquid formulation of a drug into a portion of the subject's brain through an infusion lumen at a rate of 5, 4, 3, 2, or 1 ml or less per day ±50%. The infusion may be constant and corrected by aspirating fluid from the patient's brain and testing the aspirated fluid for drug concentration. The rate of infusion by the formulation and the concentration of drug may be adjusted based on patient responsiveness.

What is claimed is: 
     
         1 . A method of treating a subject, comprising:
 positioning a portion of a device into a subject's brain;   infusing a liquid formulation of a drug into a portion of a subject's brain fluid through an infusion lumen at a rate of 5 ml per day or less.   
     
     
         2 . The method of  claim 1 , wherein the rate is 4 ml per day or less. 
     
     
         3 . The method of  claim 1 , wherein the rate is 1 ml per day ±50%. 
     
     
         4 . The method of  claim 1 , wherein the infusion rate is less than 3 ml per day and greater than 0.1 ml per day with drug in the formulation at a concentration in a range of from 10 mg/ml to 500 mg/ml. 
     
     
         5 . The method of  claim 1 , further comprising:
 continuing the infusing for a period of one month or more.   
     
     
         6 . The method of  claim 5 , wherein the infusion rate is substantially constant over one month. 
     
     
         7 . The method of  claim 1 , further comprising:
 aspirating a sample of fluid from the subject's brain, that sample having a volume of 3 ml or less;   determining the drug level in the sample; and   adjusting the rate of infusion of the liquid formulation based on the determined drug level in the sample fluid.   
     
     
         8 . The method of  claim 1 , further comprising:
 selecting a subject patient suffering from epilepsy which patient is non-responsive to treatment with oral anti-epileptic drugs.   
     
     
         9 . The method of  claim 8 , further comprising:
 selecting patient with a severe form of epilepsy in danger of brain damage or death.   
     
     
         10 . The method of  claim 1 , wherein the patient has been diagnosed with a neurological disease selected from the group consisting of:
 post-traumatic stress disorder (PTSD) bipolar disorder, brain cancer, Alzheimer's diseases, Parkinson's diseases, closed head injury, stroke, multiple sclerosis, depression, schizophrenia, and anxiety.   
     
     
         11 . A method of treatment, comprising:
 diagnosing a patient as having a refractory form of epilepsy which patient is non-responsive to oral administration of a drug;   administering a solution of an anti-epileptic drug directly to the brain of the patient at a rate of 5 ml per day or less via an implantable infusion pump system;   continuing the administering over a period of days;   extracting fluid from the brain of the patient;   determining a concentration of drug in the fluid extracted;   adjusting the administering based on the concentration.   
     
     
         12 . A method of treating a subject suffering from a neurological disorder, comprising:
 inserting a catheter through the skull of a patient wherein the catheter is comprised of an infusion lumen which delivers a drug solution directly to the subject's brain, and an aspiration lumen which withdraws fluid from the subject's brain;   delivering a drug solution to the subject's brain via the infusion lumen at a rate of 5 ml per day or less;   withdrawing fluid from the patient's brain via the aspiration lumen, wherein a proximal end of the aspiration lumen is connected to a container.   
     
     
         13 . The method as claimed in  claim 12 , wherein the neurological disorder is selected from the group consisting of post-traumatic stress disorder (PTSD) bipolar disorder, brain cancer, Alzheimer's disease, Parkinson's disease, closed head injury, stroke, multiple sclerosis, depression, schizophrenia, and anxiety; and
 wherein the patient has been determined as non-responsive to treatment with oral medication.   
     
     
         14 . The method as claimed in  claim 13 , wherein the drug is selected from the group consisting of valproic acid, benzodiazepine, lithium, irinotecan, Beta amyloid secretase inhibitors, tau protein antibodies, glial derived neurotrophic factor (GDNF), Glatiramer acetate, beta interferences, MAOi monoamine oxidase, TCA tricyclic antidepressants, clozapine, clozanezapam, and isocarboxazid. 
     
     
         15 . The method of  claim 12 , wherein the aspiration lumen is used only for sampling of the subject's brain fluid and is positioned such that a distal end of the aspiration lumen and a distal end of the infusion lumen are positioned away from one another. 
     
     
         16 . The method of  claim 12 , wherein the rate is 1 ml per day ±50% and drug is in the drug solution at a concentration in a range of 10 mg/ml to 500 mg/ml, ±20%. 
     
     
         17 . The method of  claim 12 , wherein the drug is an anti-epileptic drug selected from the group consisting of:
 Carbatrol, Epitol, Equetro, Tegretol (carbamazepine);   Gabitril (tiagabine);   Keppra (levetiracetam);   Lamictal (lamotrigine);   Lyrica (pregabalin);   Fenfluramine;   Gralise, Horizant, Neurontin, Gabarone (gabapentin);   Dilantin, Prompt, Di-Phen, Epanutin, Phenytek (phenytoin);   Topamax, Qudexy XR, Trokendi XR, Topiragen (topiramate);   Trileptal, Oxtellar (oxcarbazepine);   Depacon, Depakene, Depakote, Stavzor (valproate, valproic acid);   Zonegran (zonisamide);   Fycompa (perampanel);   Aptiom (eslicarbazepine acetate);   Vimpat (lacosamide);   Sabril (vigabatrin);   Banzel, Inovelon (rufinamide);   Cerebyx (fosphenytoin);   Zarontin (ethosuximide);   Solfoton, Luminal (phenobarbital);   Valium, Diastat (diazepam);   Ativan (lorazepam);   Lonopin, Klonopin (clonazepam);   Frisium, Onfi (clobazam);   Potiga (ezogabine);   Felbatol (felbamate);   Mysoline (primidone);   Acetazolamide;   Brivaracetam;   Clorazepate;   Ethotoin;   Mephenytoin;   Methsuximide;   Trimethadione; and   Bumetanide;   Adenosine; and   Adenosine a1 receptor agonists;   wherein the patient has been determined as non-responsive to treatment with oral medication.   
     
     
         18 . The method of  claim 12 , wherein outer surfaces of the catheter are coated with biocompatible materials which inhibit cell adhesion and/or comprises an antimicrobial. 
     
     
         19 . The method of  claim 12 , further comprising:
 withdrawing fluid from the subject's brain with the aspiration lumen;   testing fluid withdrawn; and   modifying the rate of infusion based on an analysis of the fluid tested.   
     
     
         20 . A package, comprising:
 a catheter including an aspiration lumen, an infusion lumen, wherein a distal end of the catheter is positionable during use, in a subject's brain fluid;   a container coupled to a proximal end of the aspiration lumen, wherein the proximal end of the aspiration lumen is in fluid communication with the container;   a pump which pumps a drug solution into the patient's brain at an infusion rate of 5 ml per day or less;   a liquid solution of a drug present in a drug container;   instructions for using the drug for treating a neurological disease in a patient in need of treatment, the instructions indicating the patient must be determined nonresponsive to or noncompliant with oral medication.