Darunavir/Ritonavir Pharmacokinetics Following Coadministration With Clarithromycin in Healthy Volunteers

  title={Darunavir/Ritonavir Pharmacokinetics Following Coadministration With Clarithromycin in Healthy Volunteers},
  author={Vanitha J. Sekar and Sabrina Spinosa‐Guzman and Els De Paepe and Martine De Pauw and Tony J Vangeneugden and {\'E}ric Lefebvre and Richard M. W. Hoetelmans},
  journal={The Journal of Clinical Pharmacology},
This study investigated the steady‐state pharmacokinetic interaction between the HIV protease inhibitor, darunavir (TMC114), administered with low‐dose ritonavir (darunavir/ritonavir), and clarithromycin in HIV‐negative healthy volunteers. In a 3‐way crossover study, 18 individuals received darunavir/ritonavir 400/100 mg bid, clarithromycin 500 mg bid, and darunavir/ritonavir 400/100 mg bid plus clarithromycin 500 mg bid in 3 separate sessions for 7 days, with a washout period of at least 7… 

The Effect of Lopinavir/Ritonavir and Darunavir/Ritonavir on the HIV Integrase Inhibitor S/GSK1349572 in Healthy Participants

Treatment comparisons of steady‐state S/ GSK1349572 PK parameters demonstrated that coadministration of lopinavir/ritonavir had no significant effect on steady‐ state PK of S/GSK13 49572, and coadministration of darunavir /rit onavir resulted in a nonclinically significant reduction in steady-state plasma S /GSK 1349572 exposures.

Pharmacokinetic evaluation of the interaction between etravirine and rifabutin or clarithromycin in HIV-negative, healthy volunteers: results from two Phase 1 studies.

Etravirine can be coadministered with 300 mg of rifabutin once daily in the absence of an additional potent cytochrome P450 inducer, but alternatives to clarithromycin are recommended when used for Mycobacterium avium complex prophylaxis or treatment.

Management of Antiretroviral Therapy with Boosted Protease Inhibitors—Darunavir/Ritonavir or Darunavir/Cobicistat

Current information on the pharmacokinetics, pharmacology, drug interactions, and adverse reactions of darunavir is presented; it not only compares the bioavailability, pharmacokinetic parameters, immunological and virological responses, but also the efficacy, advantages, and therapeutic disadvantages of DRV/COBI orDRV/RTV combinations.

Pharmacotherapy Update: Treatment of HIV Infection with Darunavir

In HIV infected adults, the pharmacokinetic profile of darunavir showed that the drug concentrations are similar in the age range between 18 to 65 years and unaffected by the presence of moderate renal or hepatic function impairment.

Darunavir: in treatment-experienced pediatric patients with HIV-1 infection.

Boosted darunavir was generally well tolerated in the DELPHI trial, with a similar profile to that observed in adults, and the mean triglyceride level at week 48 was lower than that at baseline, and cholesterol levels increased slightly but remained within the normal range.

Darunavir: an effective protease inhibitor for HIV-infected patients

Boosted darunavir was generally well tolerated, with lower incidence of diarrhea and a more favorable lipid profile than boosted lopinavir in treatment-naive patients, and Monotherapy with boosted dar unavir is an acceptable option in some specific conditions.

Darunavir: a review of its use in the management of HIV infection in adults.

Boosted darunavir is an oral nonpeptidic HIV-1 PI that selectively inhibits the cleavage of HIV gag and gag-pol polyproteins, thereby preventing viral maturation and is highly potent against laboratory strains and clinical isolates of wild-type and multidrug-resistant HIV.

Managing treatment-experienced pediatric and adolescent HIV patients: role of darunavir

Substantial data support darunavir use as a potent, well-tolerated option for salvage therapy in highly treatment-experienced children and adolescents.

Darunavir: A Critical Review of Its Properties, Use and Drug Interactions

The impact of the use of darunavir in the treatment of HIV-infected patients, its pharmacological and physical-chemical properties, its drug interactions, and challenges that remain are discussed in order to ensure safety and compliance of treatment.



Pharmacokinetic Interaction between Amprenavir and Clarithromycin in Healthy Male Volunteers

A pharmacokinetic interaction occurs when amprenavir and clarithromycin are coadministered, but the effects are not likely to be clinically important, and coadministration does not require a dosage adjustment for either drug.

Efficacy and safety of TMC114/ritonavir in treatment-experienced HIV patients: 24-week results of POWER 1

TMC114/r demonstrated statistically higher 24-week virological response rates and CD4 cell count increases than CPI(s) and has received regulatory approval in treatment-experienced patients.

Clinical Pharmacokinetics of Clarithromycin

  • K. Rodvold
  • Biology, Medicine
    Clinical pharmacokinetics
  • 1999
The pharmacokinetic and pharmacodynamic studies suggest that fewer serious drug interactions occur with clarithromycin compared with older macrolides such as erythromycin and troleandomycin.

Week 24 efficacy and safety of TMC114/ritonavir in treatment-experienced HIV patients

TMC114/r treatment resulted in greater virological and immunological responses in ART-experienced patients compared with CPI at 24 weeks, and more patients in each TMC 114/r dose group achieved ≥ 1.0 log10 copies/ml reduction in HIV-1 RNA than in the CPI group.

Pharmacokinetic interaction between ritonavir and clarithromycin *

The management of HIV-1 protease inhibitor pharmacokinetic interactions.

This review will focus on the current use of PIs, highlighting some important management issues encountered with common pharmacokinetic interactions seen in clinical practice.

Clarithromycin. A review of its efficacy in the treatment of respiratory tract infections in immunocompetent patients.

Clarithromycin provides similar clinical and bacteriological efficacy to that seen with beta-lactam agents, cephalosporins and other macrolides and is available in both once-daily and twice-daily formulations.

The role of newer macrolides in the treatment of community-acquired respiratory tract infection. A review of experimental and clinical data.

Clinical experience with clarithromycin and azithromyc suggests that these agents have limited efficacy against certain respiratory infections, and they may no longer be an appropriate choice for first-line therapy.

Novel bis-Tetrahydrofuranylurethane-Containing Nonpeptidic Protease Inhibitor (PI) UIC-94017 (TMC114) with Potent Activity against Multi-PI-Resistant Human Immunodeficiency Virus In Vitro

Considering the favorable pharmacokinetics of UIC-94017 when administered with ritonavir, the present data warrant that UIC -94017 be further developed as a potential therapeutic agent for the treatment of primary and multi-PI-resistant HIV-1 infections.