Naphthalimide Dosing by N-Acetyl Transferase Genotyping
The present invention provides methods for dosing patients with naphthalimides, including amonafide, amonafide salts, and analogs thereof based on N-acetyl transferase genotyping. The invention also provides methods for dosing the amount of granulocyte colony stimulating factor (GCSF) used in combination with naphthalimide to prevent or modulate leukocytopenia.
1 . A method for dosing a patient with a naphthalimide comprising:
genotyping a patient for an N-acetyl transferase genotype to provide an indication of the phenotype of said patient to rapidly or slowly acylate a naphthalimide; and
determining the dose of napthalimide to be administered to said patient.
2 . A method for dosing a patient with a naphthalimide comprising:
genotyping a patient for an N-acetyl transferase genotype to provide an indication of the phenotype of said patient to rapidly or slowly acylate a naphthalimide; and
administrating a naphthalimide to said patient at a dose that is dependent upon the acylation phenotype.
3 . The method of claim 1 or 2 wherein said naphthalimide is amonafide.
4 . The method of claim 2 wherein a higher amount of naphthalimide is administered to a patient with a slow acylation phenotype as compared to a fast acylator phenotype.
5 . The method of claim 2 wherein a lower dose of the naphthalimide is administered to a patient with a fast acylation phenotype as compared to a slow acylator phenotype.
6 . The method of claim 1 further comprising determining the dose of granulocyte colony stimulating factor (GCSF) to be administered to said patient based on the determination of said fast or slow acylation phenotype to treat leukocytopenia associated with administration of said naphthalimide.
7 . The method of claim 2 further comprising administering a dose of granulocyte colony stimulating factor (GCSF) based on the determination of said fast or slow acylation phenotype to treat leukocytopenia associated with administration of said naphthalimide.
8 . The method of claim 7 wherein said GCSF is administered contemporaneously with said naphthalimide.
9 . The method of claim 7 wherein said GCSM is administered prior to said naphthalimide.
10 . The method of claim 7 wherein said GSCSF is administered after the administration of said naphthalimide.
11 . The method of claim 7 further comprising administering an anti-proliferative agent to said patient before, during or after the administration of either of said naphthalimide or said GSCSF.
12 . A composition comprising a naphthalimide and GCSF.
13 . A composition according to claim 12 wherein said naphthalimide is amonafide.
14 . The composition of claim 12 further comprising anti-proliferative agent.
15 . A kit for N-acetyl transferase genotyping comprising:
at least one nucleic acid capable of distinguishing at least one allele of a genotype of N-acetyl transferase; and
at least one reagent or label required for said genotyping.
16 . The kit of claim 15 wherein one or more reagents include a DNA polymerase for carrying out a polymerase chain reaction (PCR).
17 . A kit comprising naphthalimide and GCSF.
18 . The kit of claim 17 further comprising an anti-proliferative agent.