Drug-Drug Interaction between the Direct-Acting Antiviral Regimen of Ombitasvir-Paritaprevir-Ritonavir plus Dasabuvir and the HIV Antiretroviral Agent Dolutegravir or Abacavir plus Lamivudine
| Autor: | Weihan Zhao, Roger Trinh, Amit Khatri, Rajeev M. Menon, Thomas Podsadecki |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Cyclopropanes
Male HIV Infections Pharmacology 030226 pharmacology & pharmacy Piperazines chemistry.chemical_compound 0302 clinical medicine Abacavir 2-Naphthylamine Anilides Drug Interactions Pharmacology (medical) 030212 general & internal medicine Sulfonamides Dasabuvir Lamivudine Valine Middle Aged Drug Combinations Infectious Diseases Anti-Retroviral Agents Dolutegravir Female Heterocyclic Compounds 3-Ring medicine.drug Adult Macrocyclic Compounds Proline Anti-HIV Agents Pyridones Lactams Macrocyclic Antiviral Agents 03 medical and health sciences Ombitasvir/paritaprevir/ritonavir Oxazines medicine Humans Uracil Ritonavir business.industry Hepatitis C Chronic Dideoxynucleosides Regimen chemistry Paritaprevir Carbamates business |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 60:6244-6251 |
| ISSN: | 1098-6596 0066-4804 |
| Popis: | The direct-acting antiviral regimen of 25 mg ombitasvir–150 mg paritaprevir–100 mg ritonavir once daily (QD) plus 250 mg dasabuvir twice daily (BID) is approved for the treatment of hepatitis C virus genotype 1 infection, including patients coinfected with human immunodeficiency virus. This study was performed to evaluate the pharmacokinetic, safety, and tolerability effects of coadministering the regimen of 3 direct-acting antivirals with two antiretroviral therapies (dolutegravir or abacavir plus lamivudine). Healthy volunteers ( n = 24) enrolled in this phase I, single-center, open-label, multiple-dose study received 50 mg dolutegravir QD for 7 days or 300 mg abacavir plus 300 mg lamivudine QD for 4 days, the 3-direct-acting-antiviral regimen for 14 days, followed by the 3-direct-acting-antiviral regimen with dolutegravir or abacavir plus lamivudine for 10 days. Pharmacokinetic parameters were calculated to compare combination therapy with 3-direct-acting-antiviral or antiretroviral therapy alone, and safety/tolerability were assessed throughout the study. Coadministration of the 3-direct-acting-antiviral regimen increased the geometric mean maximum plasma concentration ( C max ) and the area under the curve (AUC) of dolutegravir by 22% (central value ratio [90% confidence intervals], 1.219 [1.153, 1.288]) and 38% (1.380 [1.295, 1.469]), respectively. Abacavir geometric mean C max and AUC values decreased by 13% (0.873 [0.777, 0.979]) and 6% (0.943 [0.901, 0.986]), while those for lamivudine decreased by 22% (0.778 [0.719, 0.842]) and 12% (0.876 [0.821, 0.934]). For the 3-direct-acting-antiviral regimen, geometric mean C max and AUC during coadministration were within 18% of measurements made during administration of the 3-direct-acting-antiviral regimen alone, although trough concentrations for paritaprevir were 34% (0.664 [0.585, 0.754]) and 27% (0.729 [0.627, 0.847]) lower with dolutegravir and abacavir-lamivudine, respectively. All study treatments were generally well tolerated, with no evidence of increased rates of adverse events during combination administration. These data indicate that the 3-direct-acting-antiviral regimen can be administered with dolutegravir or abacavir plus lamivudine without dose adjustment. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|