JPWO2019234240A5

JPWO2019234240A5 -

Info

Publication number: JPWO2019234240A5
Application number: JP2020568390A
Authority: JP
Publication date: 2022-06-15

Claims

A pharmaceutical composition for treating or preventing a disease, which comprises a pharmaceutically effective amount of a β-lactam compound or a pharmaceutically acceptable salt thereof, and probenecid or a pharmaceutically acceptable salt thereof.
A pharmaceutical composition in which the β-lactam compound or a pharmaceutically acceptable salt thereof and the probenecid or a pharmaceutically acceptable salt thereof are administered by the same route of administration.

The pharmaceutical composition according to claim 1, wherein the β-lactam compound or a pharmaceutically acceptable salt thereof and the probenecid or a pharmaceutically acceptable salt thereof are administered over a certain period of time.

The period is longer than about 24 hours;
Is the period about 2 to about 30 days, about 3 to about 20 days, about 4 to about 15 days, about 5 to about 10 days, or about 6 to about 8 days; or the above. The pharmaceutical composition according to claim 2, which has a period of about 7 days.

The plasma concentration of the β-lactam compound of the subject to which the pharmaceutical composition was administered was the equivalent subject (eg, said equivalent) to which the β-lactam compound and probenecid were administered without food as a result of the administration. Subjects are fasting), within about 30 minutes, or within 1 hour, or within approximately 2 hours, or within approximately 3 hours, or within approximately 6 hours, or within approximately 12 hours, or Within approximately 18 hours, or within approximately 1 day, or within approximately 2 days, or within approximately 3 days, or within approximately 4 days, or within approximately 5 days, or within approximately 6 days, or within approximately 7 days, approximately 5 % Or more, or about 10% or more, or about 20% or more, or about 30% or more, or about 40% or more, or about 50% or more, or about 55% or more, or about 60% or more, or about 65% or more. , Or about 70% or more, or about 100% or more, or about 150% or more, or about 200% or more, or about 300% or more, or about 400% or more, or about 500% or more large sub-curve area (AUC) The pharmaceutical composition according to any one of claims 1 to 3.

The diseases are simple urinary tract infection, complicated urinary tract infection, complicated intraperitoneal infection, pneumonia, middle ear inflammation, sinusitis, gonococcal urinary tract inflammation, pelvic inflammatory disease, prostatic inflammation, bone infection. , Joint infection, diabetic foot disease infection, infectious diarrhea, the pharmaceutical composition according to any one of claims 1 to 4.

The β-lactam compound is a compound of the formula (I), (Ia), or (Ib):

(In the equation, R ¹ is H or, in some cases, substituted alkyl),
The pharmaceutical composition according to any one of claims 1 to 5, which is a salt acceptable as the pharmaceutically acceptable salt.

The β-lactam compound is a compound of the formula (III), (IIIa), or (IIIb):

(In the equation, R ² is H or, in some cases, substituted alkyl),
The pharmaceutical composition according to any one of claims 1 to 5, which is a salt that is acceptable as a pharmaceutical thereof.

The β-lactam compound is

The pharmaceutical composition according to claim 9, which is selected from the group consisting of salts that are acceptable as the pharmaceutically acceptable salt thereof.

The pharmaceutical composition according to any one of claims 1 to 8, wherein the β-lactam compound or a pharmaceutically acceptable salt thereof and the probenecid or a pharmaceutically acceptable salt thereof are administered as a combination drug.

The pharmaceutical composition according to claim 9, wherein the combination drug is administered to the subject at least once a day.

The pharmaceutical composition according to claim 10, wherein the combination drug is administered to a subject once a day, twice a day, three times a day, or four times a day.

The combination drug
20 mg to about 5 g, or about 50 mg to about 2 g, or about 80 mg to about 1 g, or about 100 mg to about 900 mg, or about 900 mg of the β-lactam compound or a pharmaceutically acceptable salt thereof. 200 mg to about 800 mg, or about 300 mg to about 700 mg, or about 400 mg to about 600 mg, or about 450 mg to about 550 mg, or about 480 mg to about 520 mg;
20 mg to about 5 g, or about 50 mg to about 2 g, or about 80 mg to about 1 g, or about 100 mg to about 900 mg, or about 200 mg to the pharmaceutically acceptable salt of probenecid or the like. Any one of claims 9-11, comprising about 800 mg, or about 300 mg to about 700 mg, or about 400 mg to about 600 mg, or about 450 mg to about 550 mg, or about 480 mg to about 520 mg. The pharmaceutical composition according to the section.

The pharmaceutical composition according to claim 12, wherein the combination drug contains about 500 mg of the β-lactam compound or a pharmaceutically acceptable salt thereof and about 500 mg of the probenecid or a pharmaceutically acceptable salt thereof.

As a result of administration of the mixture, the plasma concentration of β-lactam compound is about 4325 ± 3000 ng · hour / ml, or about 4325 ± 2500 ng · hour / ml, or about 1 day after administration. 4325 ± 2000 ng · hours / ml, or about 4325 ± 1500 ng · hours / ml, or about 4325 ± 1000 ng · hours / ml, or about 4325 ± 900 ng · hours / ml, or about 4325 ± 800 ng · hours / ml, or about 4325 ± 700 ng · hours / ml, or about 4325 ± 600 ng · hours / ml, or about 4325 ± 500 ng · hours / ml, or about 4325 ± 400 ng · hours / ml, or about 4325 ± 300 ng · hours / ml, or about 4325 ± 200 ng · hours / ml, or about 4325 ± 100 ng · hours / ml, or about 4325 ± 90 ng · hours / ml, or about 4325 ± 80 ng · hours / ml, or about 4325 ± 70 ng · hours / ml, or about 4325 ± 60 ng · hours / ml, or about 4325 ± 50 ng · hours / ml, or about 4325 ± 40 ng · hours / ml, or about 4325 ± Claimed to have an area under the curve (AUC) of 30 ng · hour / ml, or about 4325 ± 20 ng · hour / ml, or about 4325 ± 10 ng · hour / ml (eg, about 4325 ng · hour / ml). 13. The pharmaceutical composition according to 13.

As a result of administration of the mixture, the plasma concentration of β-lactam compound is about 7340 ± 3000 ng · hour / ml, or about 7340 ± 2500 ng · hour / ml, or about 1 day after administration. 7340 ± 2000 ng · hours / ml, or about 7340 ± 1500 ng · hours / ml, or about 7340 ± 1000 ng · hours / ml, or about 7340 ± 900 ng · hours / ml, or about 7340 ± 800 ng · hours / ml, or about 7340 ± 700 ng · hours / ml, or about 7340 ± 600 ng · hours / ml, or about 7340 ± 500 ng · hours / ml, or about 7340 ± 400 ng · hours / ml, or about 7340 ± 300 ng · hours / ml, or about 7340 ± 200 ng · hours / ml, or about 7340 ± 100 ng · hours / ml, or about 7340 ± 90 ng · hours / ml, or about 7340 ± 80 ng · hours / ml, or about 7340 ± 70 ng · hours / ml, or about 7340 ± 60 ng · hours / ml, or about 7340 ± 50 ng · hours / ml, or about 7340 ± 40 ng · hours / ml, or about 7340 ± Claimed to have an area under the curve (AUC) of 30 ng · hour / ml, or about 7340 ± 20 ng · hour / ml, or about 7340 ± 10 ng · hour / ml (eg about 7340 ng · hour / ml). 13. The pharmaceutical composition according to 13.

The combination may be used for about 1 day, or about 2 days, or about 3 days, or about 4 days, or about 5 days, or about 6 days, or about 7 days, or about 14 days, or about 21 days, or 13. Pharmaceutical composition.

The pharmaceutical composition according to any one of claims 9 to 16, wherein the combination is an oral combination.

The pharmaceutical composition according to claim 17, wherein the combination drug is a tablet.

The pharmaceutical composition according to any one of claims 1 to 8, wherein the β-lactam compound or a pharmaceutically acceptable salt thereof and the probenecid or a pharmaceutically acceptable salt thereof are administered at the same time.

The β-lactam compound or a pharmaceutically acceptable salt thereof is at least once a day, about 20 mg to about 5 g, or about 50 mg to about 2 g, or about 80 mg to about 1 g, or about. 100 mg to about 900 mg, or about 200 mg to about 800 mg, or about 300 mg to about 700 mg, or about 400 mg to about 600 mg, or about 450 mg to about 550 mg, or about 480 mg to about 520 With daily doses in the range of mg
19. The pharmaceutical composition of claim 19, preferably administered at a daily dose of about 500 mg.

The β-lactam compound or a pharmaceutically acceptable salt thereof at least once a day, about 50 mg to about 10 g, or about 100 mg to about 5 g, or about 200 mg to about 3 g, or about. With daily doses ranging from 400 mg to about 2 g, or about 600 mg to about 1.5 g, or about 800 mg to about 1.2 g, or about 900 mg to about 1.1 g.
19. The pharmaceutical composition of claim 19, preferably administered at a daily dose of about 1 g.

The pharmaceutical composition according to any one of claims 1 to 8 and 19 to 21, wherein the β-lactam compound or a pharmaceutically acceptable salt thereof is administered twice a day.

The probenecid or a pharmaceutically acceptable salt thereof is at least once a day, about 20 mg to about 5 g, or about 50 mg to about 2 g, or about 80 mg to about 1 g, or about 100 mg to. Range of about 900 mg, or about 200 mg to about 800 mg, or about 300 mg to about 700 mg, or about 400 mg to about 600 mg, or about 450 mg to about 550 mg, or about 480 mg to about 520 mg With a daily dose of
The pharmaceutical composition according to any one of claims 1 to 8 and 19 to 22, preferably administered at a daily dose of about 500 mg.

The probenecid or a pharmaceutically acceptable salt thereof is at least once a day, about 50 mg to about 10 g, or about 100 mg to about 5 g, or about 200 mg to about 3 g, or about 400 mg to. At daily doses ranging from about 2 g, or about 600 mg to about 1.5 g, or about 800 mg to about 1.2 g, or about 900 mg to about 1.1 g,
The pharmaceutical composition according to any one of claims 1 to 8 and 19 to 22, preferably administered at a daily dose of about 1 g.

The pharmaceutical composition according to any one of claims 1 to 8 and 19 to 24, wherein the probenecid or a pharmaceutically acceptable salt thereof is administered twice a day.

The subject to which the pharmaceutical composition is administered is within about 1 hour, or within about 2 hours, or within about 3 hours, or within about 6 hours, or within about 12 hours, or within about 24 hours, or about 2 before administration. The pharmaceutical composition according to any one of claims 1 to 25, which is not fasted within a day, about 5 days, or within about 10 days.

The pharmaceutical composition according to claim 26, wherein the subject of administration of the pharmaceutical composition is to be fed before administration.

The pharmaceutical composition according to any one of claims 1 to 25, wherein the subject of administration of the pharmaceutical composition is fasted before administration.

The subject to which the pharmaceutical composition is administered is within about 1 hour, or within about 2 hours, or within about 3 hours, or within about 6 hours, or within about 12 hours, or within about 24 hours, or about 2 before administration. 28. The pharmaceutical composition according to claim 28, which is fasted within a day, or within about 5 days, or within about 10 days.