生物活性
Dolutegravir (DTG) is a second-generation integrase strand transfer inhibitor (INSTI) and INSTIs are the latest class of potent anti-HIV drugs.Compared to the first generation INSTIs, raltegravir, and elvitegravir, Dolutegravir shows a limited cross-resistance profile.More interestingly, clinical resistance mutations to Dolutegravir in treatment-naive patents have not been observed to this date.Dolutegravir is a dominant strategy in the management of TN and TE patients when compared to recommended comparators.Dolutegravir had no effect on NGM/EE PK or PD. NGM/EE can be administered with DTG without dose adjustment.Dolutegravir is the integrase inhibitor of choice for rescue therapy in multiresistant HIV infection, both in integrase inhibitor-naïve patients and in those previously treated with raltegravir or elvitegravir.Treatment with DTG led to less HIV-1 genetic and amino-acid diversification over time, as compared to treatment with RAL or the absence of drug.
不同实验动物依据体表面积的等效剂量转换表(数据来源于FDA指南)
|
小鼠 |
大鼠 |
兔 |
豚鼠 |
仓鼠 |
狗 |
重量 (kg) |
0.02 |
0.15 |
1.8 |
0.4 |
0.08 |
10 |
体表面积 (m2) |
0.007 |
0.025 |
0.15 |
0.05 |
0.02 |
0.5 |
Km 系数 |
3 |
6 |
12 |
8 |
5 |
20 |
动物 A (mg/kg) = 动物 B (mg/kg) × |
动物 B的Km系数 |
动物 A的Km系数 |
例如,依据体表面积折算法,将白藜芦醇用于小鼠的剂量22.4 mg/kg 换算成大鼠的剂量,需要将22.4 mg/kg 乘以小鼠的Km系数(3),再除以大鼠的Km系数(6),得到白藜芦醇用于大鼠的等效剂量为11.2 mg/kg。
化学数据
分子量 |
441.36 |
分子式 |
C20H18F2N3NaO5 |
CAS号 |
1051375-19-9 |
纯度 |
99.46% |
溶解性(25°C) |
DMSO >80 mg/ml |
储存和运输条件 |
固体粉末: -20°C 冷藏长期储存 常温运输及临时存放 |
储备液配制
以下数据基于产品分子量,对于特殊产品,请参照COA中的储备液配制条件和说明进行操作。
Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
1 mM |
2.2657 mL |
11.3286 mL |
22.6572 mL |
5 mM |
0.4531 mL |
2.2657 mL |
4.5314 mL |
10 mM |
0.2266 mL |
1.1329 mL |
2.2657 mL |
参考文献
Cost-Effectiveness of Dolutegravir in HIV-1 Treatment-Naive and Treatment-Experienced Patients in Canada.
Despiégel N, et al. Infect Dis Ther. 2015 Jun 23. PMID: 26099626.
Will drug resistance against dolutegravir in initial therapy ever occur?
Wainberg MA, et al. Front Pharmacol. 2015 Apr 29;6:90. PMID: 25972810.
Dolutegravir Has No Effect on the Pharmacokinetics of Oral Contraceptives With Norgestimate and Ethinyl Estradiol.
Song IH, et al. Ann Pharmacother. 2015 Jul;49(7):784-9. PMID: 25862012.
[Efficacy of dolutegravir in treatment-experienced patients: the SAILING and VIKING trials].
Moreno S, et al. Enferm Infecc Microbiol Clin. 2015 Mar;33 Suppl 1:26-30. PMID: 25858609.
Dolutegravir inhibits HIV-1 Env evolution in primary human cells.
Mesplède T, et al. AIDS. 2015 Mar 27;29(6):659-65. PMID: 25849829.