14 May 2009
Population pharmacokinetics of ritonavir-boosted atazanavir in HIV-infected patients and healthy volunteers.
Back D et al. J
Antimicrob Chemother 2009 Mar 28. [Epub ahead of print]
• This study reports the development and validation of a population pharmacokinetic model to describe ATV/r concentrations (300/100 mg once daily), identify important covariates and evaluate the predictive performance of the model for lower, unlicensed ATV doses (150 and 200 mg once daily) boosted with ritonavir (100 mg once daily).
• A one-compartment model with first-order absorption and lag-time best described the data. RTV AUC0–24 was the only significant covariate. Overall, 94–97% of observed concentrations were within the 95% prediction intervals for all three regimens.
• Conclusions: RTV AUC0–24 was significantly associated with ATV apparent oral clearance.
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25 June 2009
A randomized trial comparing plasma drug concentrations and efficacies between 2 nonnucleoside reverse-transcriptase inhibitor-based regimens in HIV-infected patients receiving rifampicin: the N2R Study.
Manosuthi W, Sungkanuparph S, Tantanathip P et al.
Clin Infect Dis 2009;48:1752–9.
• This clinical trial (N2R) in patients with concurrent HIV-1 and TB infection receiving rifampicin compared EFV- and NVP-based ART.
• At weeks 6 and 12, the mean (± SD) concentrations 12 hours after dosing for EFV were 4.27±4.49 and 3.54±3.78 mg/L, respectively, and for NVP were 5.59±3.48 and 5.6±2.65 mg/L, respectively.
• At week 12, 3.1% of EFV patients and 21.3% NVP patients had drug concentrations that were less than the recommended minimum concentrations (OR: 8.396; 95% CI: 1.808–38.993; p=0.002).
• Conclusions. EFV-based ART was less compromised by concomitant use of rifampicin than NVP-based ART in patients with concurrent HIV-1 and TB infection. Low drug exposure and low body weight were important predictive factors for treatment failure.
Link
25 June 2009
Efavirenz and nevirapine interactions with rifampicin: resolving the dilemmas?
Lalloo UG.
Clin Infect Dis 2009;48:1760–2.
• This clinical trial (N2R) in patients with concurrent HIV-1 and TB infection receiving rifampicin compared EFV- and NVP-based ART.
• At weeks 6 and 12, the mean (± SD) concentrations 12 hours after dosing for EFV were 4.27±4.49 and 3.54±3.78 mg/L, respectively, and for NVP were 5.59±3.48 and 5.6±2.65 mg/L, respectively.
• At week 12, 3.1% of EFV patients and 21.3% NVP patients had drug concentrations that were less than the recommended minimum concentrations (OR: 8.396; 95% CI: 1.808–38.993; p=0.002).
• Conclusions. EFV-based ART was less compromised by concomitant use of rifampicin than NVP-based ART in patients with concurrent HIV-1 and TB infection. Low drug exposure and low body weight were important predictive factors for treatment failure.
Link
07 June 2010
Recognition of risk for clinically significant drug interactions among HIV-infected patients receiving antiretroviral therapy.
Evans-Jones JG et al.
Clin Infect Dis 2010;50:1419–21.
• This study investigated the risk of clinically significant drug interactions in patients receiving ARVs and their recognition by clinicians.
• Clinically significant drug interactions were recorded in 27% of 159 patients, with 15% of interactions potentially lowering ARV concentrations.
• Conclusions: The risk of clinically significant drug interactions was significantly related to treatment with PIs. Only 36% of clinically significant drug interactions were correctly identified by clinicians.
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