Appearance: Solid powder
Purity: > 98%
Dolutegravir(CAS 1051375-16-6), also known as GSK1349572, is an FDA-approved drug for the treatment of HIV infection.
Dolutegravir can be used to treat HIV-infected adults who have never taken HIV therapy (treatment-naïve) and HIV-infected adults who have previously taken HIV therapy (treatment-experienced), including those who have been treated with other integrase strand transfer inhibitors. Tivicay is also approved for children ages 12 years and older weighing at least 40 kilograms (kg) who are treatment-naïve or treatment-experienced but have not previously taken other integrase strand transfer inhibitors.
1. AIDS. 2010 Nov 13;24(17):2753-5. doi: 10.1097/QAD.0b013e32833f9e36.
In-vitro phenotypic susceptibility of HIV-2 clinical isolates to the integrase
Charpentier C(1), Larrouy L, Collin G, Damond F, Matheron S, Chêne G, Nie T,
Schinazi R, Brun-Vézinet F, Descamps D; French ANRS HIV-2 Cohort (ANRS CO 05
(1)Assistance Publique-Hôpitaux de Paris, Hôpital Bichat-Claude Bernard,
Université Paris-Diderot, France.
In this study of nine clinical isolates obtained from integrase inhibitor-naïve
HIV-2-infected patients, the median EC₅₀ value for the new integrase inhibitor
S/GSK1349572 was 0.8 nM (range 0.2-1.4), and is similar to HIV-1 reference
strains. We found a seven-, 13- and 18-fold increase in EC₅₀ values to
S/GSK1349572 for the HIV-2 double (T97A + Y143C; G140S + Q148R) and triple (G140T
+ Q148R + N155H) mutants, respectively, obtained from two raltegravir-experienced
2. J Acquir Immune Defic Syndr. 2010 Nov;55(3):365-7. doi:
Lack of interaction between the HIV integrase inhibitor S/GSK1349572 and
tenofovir in healthy subjects.
Song I(1), Min SS, Borland J, Lou Y, Chen S, Ishibashi T, Wajima T, Piscitelli
(1)GlaxoSmithKline, Research Triangle Park, NC 27709, USA.
BACKGROUND: The potential for a drug interaction between S/GSK1349572 and
tenofovir disoproxil fumarate (TDF) was evaluated in an open-label, repeat dose,
3-period, drug-drug interaction study in healthy subjects.
METHODS: S/GSK1349572 was administered at 50 mg once daily for 5 days (period 1)
followed by a 6-day washout period. TDF 300 mg once daily was then administered
for 7 days (period 2). The combination of S/GSK1349572 and TDF was then
coadministered for 5 days (period 3). Pharmacokinetic parameters were determined
and compared between periods.
RESULTS: Fifteen subjects completed all periods and follow-up. S/GSK1349572 and
TDF were generally well tolerated with few adverse events reported. No clinically
significant trends in post-dose laboratory abnormalities, vital signs, or
electrocardiogram values were noted. Pharmacokinetic parameters of S/GSK1349572
and tenofovir during combination therapy were similar to those when given alone,
demonstrating no significant drug interaction. S/GSK1349572 geometric least
squares mean ratios (90% confidence interval) for AUC(0-τ), Cmax, and Cτ were
1.01 (0.908, 1.11), 0.969 (0.867, 1.08), and 0.920 (0.816, 1.04), respectively.
Tenofovir geometric least squares mean ratios (90% confidence interval) for
AUC(0-τ), Cmax, and Cτ were 1.12 (1.01, 1.24), 1.09 (0.974, 1.23), and 1.19
(1.04, 1.35), respectively.
CONCLUSION: S/GSK1349572 and TDF can be coadministered without dose adjustment.
3. Antimicrob Agents Chemother. 2010 Jan;54(1):254-8. doi: 10.1128/AAC.00842-09.
Epub 2009 Nov 2.
Pharmacokinetics and safety of S/GSK1349572, a next-generation HIV integrase
inhibitor, in healthy volunteers.
Min S(1), Song I, Borland J, Chen S, Lou Y, Fujiwara T, Piscitelli SC.
(1)Infectious Diseases MDC, GlaxoSmithKline, 5 Moore Drive, Research Triangle
Park, NC 27709, USA.
S/GSK1349572 is a novel integrase inhibitor with potent in vitro anti-HIV
activity, an in vitro resistance profile different from those of other integrase
inhibitors, and favorable preclinical safety and pharmacokinetics (PK).
Randomized, double-blind, placebo-controlled single-dose and multiple-dose, dose
escalation studies evaluated the PK, safety, and tolerability of S/GSK1349572 for
healthy subjects. In the single-dose study, two cohorts of 10 subjects each (8
active, 2 receiving placebo) received suspension doses of 2, 5, 10, 25, 50, and
100 mg in an alternating panel design. In the multiple-dose study, three cohorts
of 10 subjects each (8 active, 2 receiving placebo) received suspension doses of
10, 25, and 50 mg once daily for 10 days. A cytochrome P450 3A (CYP3A) substudy
with midazolam was conducted with the 25-mg dose. Laboratory testing, vital
signs, electrocardiograms (ECGs), and PK sampling were performed at regular
intervals. S/GSK1349572 was well tolerated. Most adverse events (AEs) were mild,
with a few moderate AEs reported. Headache was the most common AE. No clinically
significant laboratory trends or ECG changes were noted. PK was linear over the
dosage range studied. The steady-state geometric mean area under the
concentration-time curve over a dosing interval (AUC(0-tau)) and maximum
concentration of the drug in plasma (C(max)) ranged from 16.7 microg.h/ml
(coefficient of variation [CV], 15%) and 1.5 microg/ml (CV, 24%) at a 10-mg dose
to 76.8 microg.h/ml (CV, 19%) and 6.2 microg/ml (CV, 15%) at a 50-mg dose,
respectively. The geometric mean steady-state concentration at the end of the
dosing interval (C(tau)) with a 50-mg dose was 1.6 microg/ml, approximately
25-fold higher than the protein-adjusted 90% inhibitory concentration (0.064
microg/ml). The half-life was approximately 15 h. S/GSK1349572 had no impact on
midazolam exposure, indicating that it does not modulate CYP3A activity. The PK
profile suggests that once-daily, low milligram doses will achieve therapeutic