External Validation of the Bilirubin–Atazanavir Nomogram for Assessment of Atazanavir Plasma Exposure in HIV-1-Infected Patients
Journal Title: The AAPS Journal - Year 2013, Vol 15, Issue 2
Abstract
Atazanavir increases plasma bilirubin levels in a concentration-dependent manner. Due to less costly and readily available assays, bilirubin has been proposed as a marker of atazanavir exposure. In this work, a previously developed nomogram for detection of suboptimal atazanavir exposure is validated against external patient populations. The bilirubin nomogram was validated against 311 matching bilirubin and atazanavir samples from 166 HIV-1-infected Norwegian, French, and Italian patients on a ritonavir-boosted regimen. In addition, the nomogram was evaluated in 56 Italian patients on an unboosted regimen. The predictive properties of the nomogram were validated against observed atazanavir plasma concentrations. The use of the nomogram to detect non-adherence was also investigated by simulation. The bilirubin nomogram predicted suboptimal exposure in the patient populations on a ritonavir-boosted regimen with a negative predictive value of 97% (95% CI 95–100). The bilirubin nomogram and monitoring of atazanavir concentrations had similar predictive properties for detecting non-adherence based on simulations. Although both methods performed adequately during a period of non-adherence, they had lower predictive power to detect past non-adherence episodes. Using the bilirubin nomogram for detection of suboptimal atazanavir exposure in patients on a ritonavir-boosted regimen is a rapid and cost-effective alternative to routine measurements of the actual atazanavir exposure in plasma. Its application may be useful in clinical settings if atazanavir concentrations are not available.
Authors and Affiliations
Dinko Rekić, Daniel Röshammar, Martin Bergstrand, Joel Tarning, Andrea Calcagno, Antonio D’Avolio, Vidar Ormaasen, Marie Vigan, Aurélie Barrail-Tran, Michael Ashton, Magnus Gisslén, Angela Äbelö
Keywords
Related Articles
- EP ID EP681088
- DOI 10.1208/s12248-012-9440-8
- Views 50
- Downloads 0
Is any measurement method optimal for all aggregate sizes and types?
Protein-based pharmaceuticals exhibit a wide range of aggregation phenomena, making it virtually impossible to find any one analytical method that works well in all cases. Aggregate sizes cover a range from small oligome...
Impact of Osmotically Active Excipients on Bioavailability and Bioequivalence of BCS Class III Drugs
SAPP is commonly used as a food additive and mostly found in bakery products (40). SAPP can also be employed as an excipient for effervescent formulations to provide rapid disintegration of pharmaceutical products. In a...
Pharmacokinetic mAb–mAb Interaction: Anti-VEGF mAb Decreases the Distribution of Anti-CEA mAb into Colorectal Tumor Xenografts
To date, there has been little investigation of the risk for drug–drug interactions involving monoclonal antibodies. The present work examined the effects of an anti-vascular endothelial growth factor (anti-VEGF)...
Inhalation Devices and Patient Interface: Human Factors
The development of any inhalation product that does not consider the patient needs will fail. The needs of the patients must be identified and aligned with engineering options and physical laws to achieve a robust and in...
Shrinkage in Nonlinear Mixed-Effects Population Models: Quantification, Influencing Factors, and Impact
The online version of this article (doi:10.1208/s12248-012-9407-9) contains supplementary material, which is available to authorized users.