# US 2019/0167570 A1 · Intravenous administration of tramadol > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2019/0167570 A1 - Document ID: US20190167570A1 - Status: Published application - Kind: A1 - Application number: 16/269,124 - Filed: 2019-02-06 - Published: 2019-06-06 - Earliest claimed: 2015-12-22 - Assignees: Revogenex Ireland Ltd - Applicants: Revogenex Ireland Ltd - Inventors: Lucy Lu; Scott Reines; Jeffrey Ping - Web page: https://patentgrep.com/patent/US20190167570A1 ## CPC - A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)} - A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration} - A61K 31/135: having aromatic rings {, e.g. ketamine, nortriptyline (methadone A61K31/137)} - A61P 25/00: Drugs for disorders of the nervous system - A61P 25/04: Centrally acting analgesics, e.g. opioids - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract A method of treating pain, e.g., acute post-operative pain, by administering to a human patient(s) a therapeutically effective dose of tramadol intravenously in a dosing regimen which includes one or more loading doses administered at shortened intervals as compared to dosing at steady-state is disclosed. In certain embodiments, the dose of tramadol is from about 45 mg to about 80 mg and the second (and optionally) third doses are intravenously administered at intervals of from about 2 to about 3 hours, and thereafter the tramadol is intravenously administered at a dosing interval of about 4 to about 6 hours, until the patient no longer requires treatment with tramadol. In preferred embodiments, the intravenous dosing regimen provides a Cmax and AUC of tramadol is similar to the Cmax and AUC of an oral dose of 100 mg tramadol HCl given every 6 hours. In certain preferred embodiments, the dosing regimen comprises 50 mg IV tramadol at Hour 0, followed by 50 mg at Hour 2, 50 mg at hour 4, and 50 mg every 4 hours thereafter (e.g., until the patient no longer requires treatment with tramadol). ## Claims ### Claim at position 1 1-27. (canceled) ### Claim 28 A method of administering tramadol for treating acute pain in a human patient via an intravenous dosing regimen, comprising intravenously administering a first dose of tramadol to a human patient experiencing acute pain in an amount of about 50 mg; and thereafter intravenously administering additional doses of tramadol to the human patient(s) in an amount of about 50 mg tramadol at dosage intervals of about 4 hours, except that a second dose is intravenously administered as a loading dose at a shortened interval as compared to the dosage interval of about 4 hours, such that a total of 7 doses of 50 mg tramadol are intravenously administered on the first day of treatment and the intravenous tramadol is administered on subsequent days of treatment on a basis of a total of 6 doses of 50 mg tramadol per day until the intravenous tramadol administration is terminated, and wherein the tramadol is tramadol base or a pharmaceutically acceptable salt of tramadol, such that the mean Cmax concentration after administration of the third administered dose of tramadol is similar to the mean Cmax at steady-state and is similar to the mean Cmax at steady-state for a dosing regimen of 100 mg tramadol HCl administered orally every 6 hours, and such that the intravenous dosing regimen provides a steady-state Cmax and AUC of tramadol which is similar to the steady-state Cmax and AUC of 100 mg tramadol HCl given every 6 hours, and administering another analgesic before, concurrently with, or after administration of the tramadol, thereby treating the acute pain in the subject. ### Claim 29 (depends on 16) The method of claim 16, wherein the another analgesic is selected from the group consisting of an NSAID, acetaminophen, another opioid analgesic, and a combination of any of the foregoing. ### Claim 30 (depends on 28) The method of claim 28, further comprising continuing to administer additional doses of tramadol to the human patient in an amount of about 50 mg tramadol at dosage intervals of about 4 hours for at least about 44 hours after the first administered dose of tramadol, such that the intravenous dosing regimen provides a Cmax of tramadol at steady-state of about 711 ng/mL±152. ### Claim 31 (depends on 28) The method of claim 28, further comprising continuing to administer additional doses of tramadol to the human patient in an amount of about 50 mg tramadol at dosage intervals of about 4 hours for at least about 24 hours after the first administered dose of tramadol, such that the intravenous dosing regimen provides an AUC0-24 of about 9520 h*ng/ml±2106. ### Claim 32 (depends on 28) The method of claim 28, further comprising continuing to administer additional doses of tramadol to the human patient in an amount of about 50 mg tramadol at dosage intervals of about 4 hours for at least about 44 hours after the first administered dose of tramadol, such that the intravenous dosing regimen provides an AUC0-48 of about 20,540 h*ng/ml±4906. ### Claim 33 (depends on 29) The method of claim 29, wherein the another analgesic is acetaminophen. ### Claim 34 A method of administering tramadol for treating acute pain in a human patient via an intravenous dosing regimen, comprising intravenously administering a first dose of tramadol to a human patient experiencing acute pain in an amount of about 50 mg; and thereafter intravenously administering additional doses of tramadol to the human patient(s) in an amount of about 50 mg tramadol at dosage intervals of about 4 hours, except that a second dose is intravenously administered as a loading dose at a shortened interval as compared to the dosage interval of about 4 hours, such that a total of 7 doses of 50 mg tramadol are intravenously administered on the first day of treatment and the intravenous tramadol is administered on subsequent days of treatment on a basis of a total of 6 doses of 50 mg tramadol per day until the intravenous tramadol administration is terminated, and wherein the tramadol is tramadol base or a pharmaceutically acceptable salt of tramadol, such that the mean Cmax concentration after administration of the third administered dose of tramadol is similar to the mean Cmax at steady-state and is similar to the mean Cmax at steady-state for a dosing regimen of 100 mg tramadol HCl administered orally every 6 hours, and such that the intravenous dosing regimen provides a steady-state Cmax and an AUC0-48 of tramadol which is similar to the steady-state Cmax and AUC0-48 of an oral dose of 100 mg tramadol HCl given every 6 hours, wherein the tramadol is tramadol base or a pharmaceutically acceptable salt of tramadol, and administering another analgesic selected from the group consisting of an NSAID, acetaminophen, and another opioid analgesic before, concurrently with, or after administration of the tramadol, thereby treating the acute pain in the subject. ### Claim 35 (depends on 33) The method of claim 33, further comprising continuing to administer additional doses of tramadol to the human patient in an amount of about 50 mg tramadol at dosage intervals of about 4 hours for at least about 44 hours after the first administered dose of tramadol. ### Claim 36 (depends on 33) The method of claim 33, further comprising continuing to administer additional doses of tramadol to the human patient in an amount of about 50 mg tramadol at dosage intervals of about 4 hours for at least about 44 hours after the first administered dose of tramadol, such that the intravenous dosing regimen provides a Cmax of tramadol at steady-state of about 711 ng/ml±152. ### Claim 37 (depends on 33) The method of claim 33, further comprising continuing to administer additional doses of tramadol to the human patient in an amount of about 50 mg tramadol at dosage intervals of about 4 hours for at least about 24 hours after the first administered dose of tramadol, such that the intravenous dosing regimen provides an AUC0-24 of about 9520 h*ng/ml±2106. ### Claim 38 (depends on 33) The method of claim 33, further comprising continuing to administer additional doses of tramadol to the human patient in an amount of about 50 mg tramadol at dosage intervals of about 4 hours for at least about 44 hours after the first administered dose of tramadol, such that the intravenous dosing regimen provides an AUC0-48 of about 20,540 h*ng/ml±4906. ### Claim 39 A method of administering tramadol for treating acute postoperative pain in a human patient via an intravenous dosing regimen, consisting of intravenously administering a first dose of tramadol to a human patient experiencing acute postoperative pain in an amount of about 50 mg; and thereafter intravenously administering additional doses of tramadol to the human patient(s) in an amount of about 50 mg tramadol at dosage intervals of about 4 hours, except that a second dose is intravenously administered as a loading dose at a shortened interval as compared to the dosage interval of about 4 hours, a total of 7 doses of 50 mg tramadol being intravenously administered on the first day of treatment and the intravenous tramadol being administered on subsequent days of treatment on a basis of a total of 6 doses of 50 mg tramadol per day until the intravenous tramadol administration is terminated, and wherein the tramadol is tramadol base or a pharmaceutically acceptable salt of tramadol, such that such that the mean Cmax after the first dose is about 273±60 ng/mL, the mean Cmax after the second dose is about 451±65 ng/mL, and the mean Cmax concentration after administration of the third administered dose of tramadol is about 666 ng/mL±135 and the mean Cmax at steady-state is of about 711 ng/mL±152, such that the intravenous dosing regimen provides a steady-state Cmax of about 711±152 ng/ml and a Css of about 557±131 ng/ml, wherein the tramadol is tramadol base or a pharmaceutically acceptable salt of tramadol, and administering another analgesic selected from the group consisting of an NSAID, acetaminophen, and another opioid analgesic before, concurrently with, or after administration of the tramadol, thereby treating the acute pain in the subject. ### Claim 40 (depends on 38) The method of claim 38, further comprising continuing to administer additional doses of tramadol to the human patient in an amount of about 50 mg tramadol at dosage intervals of about 4 hours for at least about 44 hours after the first administered dose of tramadol. ### Claim 41 (depends on 38) The method of claim 38, further comprising continuing to administer additional doses of tramadol to the human patient in an amount of about 50 mg tramadol such that the intravenous dosing regimen provides an AUC0-24 of about 9520 h*ng/ml±2106. ### Claim 42 (depends on 38) The method of claim 38, further comprising continuing to administer additional doses of tramadol to the human patient in an amount of about 50 mg tramadol at dosage intervals of about 4 hours for at least about 44 hours after the first administered dose of tramadol, such that the intravenous dosing regimen provides an AUC0-48 of about 20,540 h*ng/ml±4906. ### Claim 43 (depends on 34) The method of claim 34, wherein the another analgesic is acetaminophen. ### Claim 44 (depends on 34) The method of claim 34, wherein the another analgesic is an NSAID. ### Claim 45 (depends on 39) The method of claim 39, wherein the another analgesic is acetaminophen. ### Claim 46 (depends on 39) The method of claim 39, wherein the another analgesic is an NSAID. ### Claim 47 (depends on 28) The method of claim 28, wherein the another analgesic is an NSAID.