Pharmacokinetics comparison of two pegylated interferon alfa formulations in healthy volunteers

Abstract

BackgroundSeveral countries have used pegylation technology to improve the pharmacokinetic properties of essential drugs. Recently, a novel interferon alfa-2b protein conjugated to four-branched 12 kDa polyethylene glycol molecules was developed jointly between Cuba and Brazil. The aim of this study was to compare the pharmacokinetic properties of BIP48 (pegylated interferon alfa-2b from Bio-Manguinhos/Fiocruz, Brazil) to those of PEGASYS® (commercially available pegylated interferon alfa-2a from Roche Pharmaceutical).MethodsThis phase I, single-centre, randomized, double-blind crossover trial enrolled 31 healthy male volunteers aged 19 to 35 who were allocated to two stages, either side of a 5-week wash-out period, with each arm lasting 14 consecutive days after subcutaneous administration of 180 μg of one formulation or the other (study or comparator). The main outcome variable was serum pegylated interferon concentrations in 15 samples collected during the course of the study and tested using an enzyme immunoassay.ResultsThere were no differences between formulations in terms of magnitude or absorption parameters. Analysis of time parameters revealed that BIP48 remained in the body significantly longer than PEGASYS® (Tmax: 73 vs. 54 h [p = 0.0010]; MRT: 133 vs. 115 h [p = 0.0324]; ke: 0.011 vs. 0.013 h(−1) [p = 0.0153]; t1/2: 192 vs. 108 h [p = 0.0218]).ConclusionBIP48 showed the expected pharmacokinetic profile for a pegylated product with a branched molecular structure. Compared to PEGASYS®, the magnitude absorption was similar, but time parameters were consistent with slower elimination. Further studies should be conducted to evaluate the clinical implications of these findings. A phase II-III repeated-dose clinical trial is ongoing to study these findings in patients with chronic hepatitis C virus infection.Trial registrationThis study is registered on the ClinicalTrials.gov platform (accession number NCT01889849). This trial was retrospectively registered in June 2013.

A 7-Years Active Pharmacovigilance Study of Adverse Drug Reactions Causing Children Admission to a Pediatric Emergency Department in Sicily

“…Indeed, this is the first study that has been carried out in Sicily and therefore it may serve as benchmark for future research and it may offer an important piece of evidence for healthcare stakeholders and government decision makers to implement the needed actions to curb the burden of the ADRs in the pediatric age. The observed rate of ED admissions related to ADRs (1.6/1000) was lower than the rate previously reported in other studies ( Lombardi et al, 2018 ). On the other hand, the rate of hospitalization due to ADRs in our pediatric population (1.0%) agrees with the ADRs related hospitalization previously reported ( Smyth et al, 2012 ).…”

“…A research teams of pharmacologists, operating in the Sicilian Pharmacovigilance Centre of the University Hospital of Messina, ED physicians and monitors reviewed all identified cases of ADRs. In particularly, this group analyzed each case of suspected ADR, to evaluate the relation between drug administration and ADR onset using the Naranjo algorithm ( Naranjo et al, 1981 ; Lombardi et al, 2018 ). Preventability of ADRs was also evaluated, using the modified Schumock and Thornton criteria ( Schumock and Thornton, 1992 ).…”

“…ED visits represent a significant source of information in terms of frequency, preventability, and seriousness of ADRs ( Lombardi et al, 2018 ). Moreover, 1/10 of in-hospital children have an ADR, 12% of them are serious ( Clavenna and Bonati, 2009 ) and 2.9% of hospitalizations were due to ADRs ( Smyth et al, 2012 ).…”

“…Several reports suggest that the rate of ADR-related ED admissions in children is lower (5%) than in adults (25%) ( Lombardi et al, 2018 ). An active monitoring system of ADR showed that neonates (< 1 years) have an higher risk of ADR appearance than children (7–14 years) ( Menniti-lppolito et al, 2000 ).…”

“…An active monitoring system of ADR showed that neonates (< 1 years) have an higher risk of ADR appearance than children (7–14 years) ( Menniti-lppolito et al, 2000 ). Antibacterial for systemic use were reported as the drugs with the highest frequency of ADRs ( Carnovale et al, 2014 ; Ferrajolo et al, 2014 ; Lombardi et al, 2018 )…”