US 5,695,751 A · Enhancing delivery of large neutral amino acid drugs

Abstract

L-amino acid oxidase is utilized to reduce the plasma level of large neutral amino acids to allow the opportunity of increased large neutral amino acid drug transport across the blood brain barrier. Preferably anti L-amino acid oxidase antibody is administered intermediate to the L-amino acid oxidase and large neutral amino acid drug administrations to deplete L-amino acid oxidase activity once the L-amino acid oxidase has caused the large neutral amino acid drug transport improving level plasma reduction of large neutral amino acids thereby to reduce or eliminate degrading of large neutral amino acid drugs by L-amino acid oxidase. The large neutral amino acid drugs include levodopa, melphalan, L-DON, azaserine, acivicin, L-alanosine and 3-(phosphonomethyl)phenylalanines. For treatment of brain tumors, the drug administration is preferably preceded by the administration of a large neutral amino acid glutathione depleting agent, e.g., L-buthionine-SR-sulfoximine. L-Amino acid oxidase is also utilized to enhance the transport of large neutral amino acid glutathione depleting agent across the blood brain barrier as an adjunct to radiation therapy of brain tumors.

Claims22

Dependent claims

A method of treatment of a patient for a brain associated disease susceptible to a large neutral amino acid drug, said method comprising:

(a) administering L-amino acid oxidase to said patient at a dosage ranging from about 1 to about 100 units/ml of plasma, which is non-toxic and which is sufficient to reduce the plasma level of large neutral amino acids from a normal level to a large neutral amino acid drug transport improving level,
(b) administering orally or parenterally a therapeutically effective amount of the large neutral amino acid drug to said patient wherein the plasma level of large neutral amino acids is reduced from the normal level, within about 2 to 36 hours after administering L-amino acid oxidase;
thereby to enhance transport of the large neutral amino acid drug across the blood brain harrier compared to where L-amino acid oxidase is not administered.

A method of treatment of a patient for a brain associated disease susceptible to a large neutral amino acid drug, said method comprising:

(a) administering L-amino acid oxidase to said patient at a dosage ranging from about 1 to about 100 units/ml of plasma, which is non-toxic and which is sufficient to reduce the plasma level of large neutral amino acids from a normal level to a large neutral amino acid drug transport improving level,
(b) administering to the patient wherein the plasma level of large neutral amino acids is reduced from the normal level and from about 1 to 30 hours after the administering in step (a), from about 1 to about 25 .mu.g anti L-amino acid oxidase antibody per unit of L-amino acid oxidase administered in step (a) to inhibit plasma L-amino acid oxidase activity so that the plasma L-amino acid oxidase activity is less than 25% of the plasma L-amino acid oxidase activity one hour after the administration of step (a),
(c) administering orally or parenterally a therapeutically effective amount of the large neutral amino acid drug to the patient wherein the plasma level of large neutral amino acids is reduced from the normal level, within about 1 to 10 hours after the administration in step (b) and within about 2 to 36 hours after the administration in step (a);
thereby to enhance transport of the large neutral amino acid drug across the blood brain barrier compared to where L-amino acid oxidase is not administered.

1 more element

Dependencies are inferred from the claim text.

Enhancing delivery of large neutral amino acid drugs

Life of this patent

Enhancing delivery of large neutral amino acid drugs

Life of this patent

Abstract

Claims22