Biotherapeutic bioanalysis: a multi-indication case study review.

A thorough understanding of the structure and biology of a biotherapeutic is crucial to defining a suitable strategy for pharmacokinetic characterization in proof-of-concept disease models, toxicology species as well as the healthy and disease indication patient populations. This manuscript summarizes parameters that impact bioanalytical strategy for over 50 biotherapeutics indicated for the treatment of oncology, rheumatoid arthritis, allergy, multiple sclerosis, hematology, metabolism and infectious disease. We have addressed numerous therapeutic modalities including chimeric, humanized and fully human monoclonal antibodies, replacement proteins, peptides and fusion proteins, including polyethylene glycol and Fc fusions, as well as antibody-drug conjugates.

Effects of multiple-dose pegylated interferon alfa-2b on the activity of drug-metabolizing enzymes in persons with chronic hepatitis C.

Purpose: To examine the effect of pegylated interferon (PEG-IFN) alfa-2b on the activity of major drug-metabolizing enzymes.

Methods: This nonrandomized, open-label, multiple-dose study examined the effects of PEG-IFN alfa-2b on the activity of CYP450 1A2, 2 C8/9, 2D6, and 3A4 enzymes and N-acetyltransferase in subjects with chronic hepatitis C. Eligible subjects received PEG-IFN alfa-2b 1.

Multiple-dose pharmacokinetics of peginterferon alfa-2b in patients with renal insufficiency.

Aim: To evaluate the safety, tolerability and multiple-dose pharmacokinetics of pegylated interferon (PEG-IFN) alfa-2b in patients with moderate or severe renal insufficiency and in those with normal renal function.

Methods: In an open-label study, subjects with normal renal function (creatinine clearance >80 ml min(-1) per 1.73 m2) and patients with moderate (30-50 ml min(-1) per 1.

The effect of multiple doses of peginterferon alfa-2b on the steady-state pharmacokinetics of methadone in patients with chronic hepatitis C undergoing methadone maintenance therapy.

This multicenter, open-label study evaluated the effects of multiple doses of peginterferon alfa-2b on the steadystate pharmacokinetics of methadone in 20 adults with hepatitis C virus infection who were enrolled in a methadone maintenance program. All subjects received peginterferon alfa-2b 1.5 mug/kg/wk for 4 weeks and maintained their normal methadone regimen.

Dose selection and population pharmacokinetics of PEG-Intron in patients with chronic myelogenous leukaemia.

Aims: To assess the dose selection using population pharmacokinetics of Pegylated Intron-alpha2b (PEG-Intron) in patients with chronic myelogenous leukaemia (CML).

Methods: PEG-Intron 3-6 microg kg(-1) was administered subcutaneously once a week and blood samples were collected up to 48 weeks of treatment. A total of 624 samples collected from 137 patients were included in the analysis.