The bridge assay detected IgM and IgG APAb reactive with common PEG sizes and derivatives at sufficient sensitivity, 15-500 ng/ml. Of subjects evaluated, 6% of PEG-IFN-λ and 9% of PEG-IFN-α subjects had persistent APAb while 60% of PEG-IFN-λ and 33% of PEG-IFN-α subjects had persistent anti-interferon antibodies (AIAb). Pre-existing APAb and AIAb prevalence was comparable (approximately 10% of subjects). APAb were earlier onset, less frequent, less persistent and lower titer than AIAb. No associated hypersensitivity events were reported.
Prescreening of serum to exclude reactive individuals resulted in successful cross-validation and the establishment of a high integrity pharmacokinetic assay in support of global clinical trials.
Maraviroc is a first-in-class CCR5 antagonist that shows potent anti-HIV-1 activity in vitro and in vivo and is well tolerated in both healthy volunteers and HIV-1-infected patients. The method for determination of maraviroc (UK-427,857) and its major metabolite (UK-408,027) in human plasma consists of a protein-precipitation procedure and analysis by liquid chromatography/tandem mass spectrometry using positive ion TurboIonSpray® ionization and multiple reaction monitoring. The assay has been validated over a concentration range of 0.500-500 ng/mL for both analytes. The determinations of maraviroc in human cerebrospinal fluid (0.500-500 ng/mL) and in urine (5.00-5000 ng/mL) have also been validated but do not include measurement of the metabolite. The validations included extraction recovery, intra-assay and inter-assay precision and accuracy, stability of stock and spiking solutions, freeze-thaw stability, matrix stability, processed-extract stability, and evaluation of potential interferences from selected medications in plasma or urine.
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