CYP4 enzymes predominantly contribute to the metabolism of lusutrombopag, especially CYP4A11 [FDA Label]. Lusutrombopag is reported to mainly undergo ω- and β-oxidation, as well as glucuronidation [A36730].
In clinical trials in patients with ITP, ALT elevations occurred in 10% to 11% of eltrombopag vs 3% to 7% of placebo treated subjects, but the elevations were usually mild and transient, resolving once eltrombopag was discontinued and sometimes even with continued use. Instances in which there was recurrence of serum enzyme elevations with restarting eltrombopag have been reported and several patients were said to have developed serious liver disease on treatment, perhaps as a result of portal vein thrombosis. Because of such reports, eltrombopag has a boxed warning about hepatotoxicity and the possibility of hepatic decompensation when treating patients with chronic hepatitis C, in which situation monitoring of liver tests is recommended. Despite this, there have been no published reports of idiosyncratic clinically apparent liver injury attributable to eltrombopag therapy in the medical literature and the clinical characteristics, timing on onset, pattern of enzyme elevations and response to withdrawal of therapy of the liver injury attributed to the drug have not been described. Furthermore, with the development of more potent antiviral agents for hepatitis C, interferon is now rarely used and the indication for concurrent use of eltrombopag for thrombocytopenia during interferon therapy is rarely encountered.
There is no known antidote for lusutrombopag: hemodialysis is not expected to enhance the elimination of lusutrombopag from the plasma as there is high protein binding. Overdose may be characterized by excessive platelet counts that may result in thrombotic and thromboembolic complications. In the event of overdose, closely monitor patients and platelet count and treat thrombotic complications in accordance with standard of care [FDA Label]. In animal and _in vitro_ studies, lusutrombopag did not display any carcinogenicity, genotoxicity, or reproductive toxicity [FDA Label].
来源:DrugBank
毒理性
蛋白质结合
露舒通伯帕的血浆蛋白结合率超过99.9% [FDA 标签]。
The plasma protein binding of lusutrombopag is more than 99.9% [FDA Label].
Lusutrombopag is rapidly absorbed following oral administration [A36730]. It exhibited a dose‐proportional pharmacokinetic profile over the single dose range of 1 mg to 50 mg, which was similar in both healthy subjects and those with chronic liver disease. A geometric mean (%CV) maximal concentration (Cmax) and area under the curve (AUC) in healthy subjects receiving 3 mg of lusutrombopag were 111 (20.4) ng/mL and 2931 (23.4) ng.hr/mL [FDA Label]. The accumulation ratios of Cmax and AUC were approximately 2 with once‐daily multiple‐dose administration, and steady‐state plasma lusutrombopag concentrations were achieved after Day 5. The time to reach peak plasma concentrations (Tmax) were approximately 6 to 8 hours after oral administration in patients with chronic liver disease [FDA Label]. Food consumption is not reported to affect the absorption and bioavailability of lusutrombopag [FDA Label].
About 1% of the administered dose of lusutrombopag undergoes urinary excretion. Fecal excretion accounted for 83% of the total dose, where 16% of the dose was excreted as unchanged parent compound [A36730].
PHARMACEUTICAL COMPOSITION CONTAINING OPTICALLY ACTIVE COMPOUND HAVING THROMBOPOIETIN RECEPTOR AGONIST ACTIVITY, AND INTERMEDIATE THEREFOR
申请人：Takayama Masami
公开号：US20100267783A1
公开（公告）日：2010-10-21
An optically active 4-phenylthiazole derivative having a thrombopoietin receptor agonist activity and a pharmaceutical composition containing the present compound as an active ingredient are created, and a platelet production regulating agent which can be orally administered is provided.
Disclosed is a pharmaceutical composition containing, as an active ingredient, an optically active compound represented by the formula:
wherein, R
1
is a halogen atom or C1-C3 alkyloxy; R
2
is C1-C8 alkyl; R
3
is C1-C8 alkyl; R
4
and R
5
are each independently a fluorine atom or chlorine atom; R
6
is C1-C3 alkyl or C1-C3 alkyloxy; * indicates that a carbon atom marked with an asterisk is an asymmetric carbon,
a pharmaceutically acceptable salt thereof, or a solvate thereof.
CRYSTAL FORM OF 4-PHENYLTHIAZOLE DERIVATIVE AND PREPARATION METHOD THEREOF
申请人：Sichuan Kelun Pharmaceutical Research
Institute Co., Ltd.
公开号：EP3808736A1
公开（公告）日：2021-04-21
The invention relates to a crystal form of 4-phenylthiazole derivative, a pharmaceutical composition comprising the same, a preparation method, and a use of the crystal form for the manufacture of a medicament for treating thrombocytopenia.
Pharmaceutical composition containing a compound having a thrombopoietin receptor agonistic activity
申请人：Shionogi & Co., Ltd.
公开号：US10085973B2
公开（公告）日：2018-10-02
The present inventor has found out that the following criteria enable to ensure an effect for increasing the platelet count while preventing an excessive increase in the platelet count;
“when the platelet count has increased by a certain amount and reached to a sufficient level of the platelet count during administration of a pharmaceutical composition containing a compound having a thrombopoietin receptor agonistic activity, administration of the pharmaceutical composition is discontinued thereafter”.
Ligand-binding fiber and cell culture substrate using said fiber
申请人：NISSAN CHEMICAL INDUSTRIES, LTD.
公开号：US10724028B2
公开（公告）日：2020-07-28
The invention provides a ligand-bonded fiber in which a ligand having affinity for a cell membrane receptor is immobilized on a fiber precursor, and a cell culture substrate capable of repeating ex vivo amplification of a cell expressing a cell membrane receptor by using the ligand-bonded fiber.
Crystal form of 4-phenylthiazole derivative and preparation method thereof
申请人：SICHUAN KELUN PHARMACEUTICAL RESEARCH INSTITUTE CO., LTD.
公开号：US11174234B2
公开（公告）日：2021-11-16
The invention relates to a crystal form of 4-phenylthiazole derivative, a pharmaceutical composition comprising the same, a preparation method, and a use of the crystal form for the manufacture of a medicament for treating thrombocytopenia.
