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The role of dolutegravir in the management of HIV infection.

Miller MM, Liedtke MD, Lockhart SM, Rathbun RC - Infect Drug Resist (2015)

Bottom Line: As a substrate of CYP 3A4, dolutegravir is affected by rifampin, efavirenz, tipranavir/ritonavir, fosamprenavir/ritonavir, and dose increase is required.Dolutegravir inhibits the organic cation transporter 2, resulting in decreased creatinine clearance with no apparent decrease in renal function.Other adverse effects are minimal but include diarrhea, headache, and nausea.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy: Clinical and Administrative Sciences, University of Oklahoma College of Pharmacy, Oklahoma City, OK, USA.

ABSTRACT
Dolutegravir is the most recent integrase strand transfer inhibitor approved for HIV-1 infection in both treatment-naïve and experienced patients. As a tricyclic carbamoyl pyridone analog, dolutegravir is rapidly absorbed and distributes through the cerebrospinal fluid. It is hepatically metabolized by uridine diphosphate glucuronosyl transferase 1A1; no inhibition or induction of cytochrome P450 enzymes is noted. As a substrate of CYP 3A4, dolutegravir is affected by rifampin, efavirenz, tipranavir/ritonavir, fosamprenavir/ritonavir, and dose increase is required. Dolutegravir inhibits the organic cation transporter 2, resulting in decreased creatinine clearance with no apparent decrease in renal function. Other adverse effects are minimal but include diarrhea, headache, and nausea. Clinical trials in treatment-naïve and experienced patients are ongoing and will be presented in this text.

No MeSH data available.


Related in: MedlinePlus

Chemical structure of Tivicay® (dolutegravir 50 mg tablets).
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f1-idr-8-019: Chemical structure of Tivicay® (dolutegravir 50 mg tablets).

Mentions: Structurally, DTG is a tricyclic carbamoyl pyridone analog and has activity against wild-type HIV subtype 1 (HIV-1), with a protein-adjusted 90% inhibitory concentration (IC90) of 0.064 μg/mL (Figure 1).10,11 DTG also exhibits activity against clinical isolates of HIV subtype 2 (IC50 of 0.18 nM).11 DTG inhibits the strand transfer reaction of HIV integrase that is necessary for annealing proviral deoxyribonucleic acid (DNA) to host chromosomal DNA by binding to divalent cations (eg, magnesium) in HIV integrase within the host nucleus.10,12


The role of dolutegravir in the management of HIV infection.

Miller MM, Liedtke MD, Lockhart SM, Rathbun RC - Infect Drug Resist (2015)

Chemical structure of Tivicay® (dolutegravir 50 mg tablets).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4340460&req=5

f1-idr-8-019: Chemical structure of Tivicay® (dolutegravir 50 mg tablets).
Mentions: Structurally, DTG is a tricyclic carbamoyl pyridone analog and has activity against wild-type HIV subtype 1 (HIV-1), with a protein-adjusted 90% inhibitory concentration (IC90) of 0.064 μg/mL (Figure 1).10,11 DTG also exhibits activity against clinical isolates of HIV subtype 2 (IC50 of 0.18 nM).11 DTG inhibits the strand transfer reaction of HIV integrase that is necessary for annealing proviral deoxyribonucleic acid (DNA) to host chromosomal DNA by binding to divalent cations (eg, magnesium) in HIV integrase within the host nucleus.10,12

Bottom Line: As a substrate of CYP 3A4, dolutegravir is affected by rifampin, efavirenz, tipranavir/ritonavir, fosamprenavir/ritonavir, and dose increase is required.Dolutegravir inhibits the organic cation transporter 2, resulting in decreased creatinine clearance with no apparent decrease in renal function.Other adverse effects are minimal but include diarrhea, headache, and nausea.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy: Clinical and Administrative Sciences, University of Oklahoma College of Pharmacy, Oklahoma City, OK, USA.

ABSTRACT
Dolutegravir is the most recent integrase strand transfer inhibitor approved for HIV-1 infection in both treatment-naïve and experienced patients. As a tricyclic carbamoyl pyridone analog, dolutegravir is rapidly absorbed and distributes through the cerebrospinal fluid. It is hepatically metabolized by uridine diphosphate glucuronosyl transferase 1A1; no inhibition or induction of cytochrome P450 enzymes is noted. As a substrate of CYP 3A4, dolutegravir is affected by rifampin, efavirenz, tipranavir/ritonavir, fosamprenavir/ritonavir, and dose increase is required. Dolutegravir inhibits the organic cation transporter 2, resulting in decreased creatinine clearance with no apparent decrease in renal function. Other adverse effects are minimal but include diarrhea, headache, and nausea. Clinical trials in treatment-naïve and experienced patients are ongoing and will be presented in this text.

No MeSH data available.


Related in: MedlinePlus