Renal Filtration, Absorption and Catabolism of Human Alpha Interferon

Bocci, Velio; Pacini, A.; Muscettola, Michela; Paulesu, Luana; Pessina, G. P.; Santiano, M; Viano, I

doi:10.1089/jir.1981.1.347

Cited by 48 publications

(18 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Using a direct approach, such as studying the filtration, absorption and excretion of human IFN-ct with an isolated and perfused rabbit kidney, Bocci et al (1981) have estimated a fractional turnover rate of 0.85 % per min per kidney, a value that is in good agreement with the renal extraction rate measured in the present experiments.…”

Section: Discussionsupporting

confidence: 84%

Renal Metabolism of Rabbit Serum Interferon

Bocci

Pacini

Muscettola

et al. 1981

Journal of General Virology

Self Cite

View full text Add to dashboard Cite

SUMMARYThree different approaches have been used to evaluate the catabolism of rabbit serum interferon (IFN) by the kidneys. Firstly, in normal rabbits the disappearance of exogenous IFN from plasma was very rapid, whereas it was significantly slower after bilateral nephrectomy. Secondly, the IFN level in arterial blood was always higher than in renal venous blood: the mean renal extraction rate of IFN in the rabbit, with a renal plasma flow of 9 ml/min, was about 1 ml/min. Thirdly, a selective and reversible tubular damage induced by maleate before intravenous administration of IFN significantly inhibited luminal uptake of IFN and markedly increases the interferonuria. All of these results support the view that the kidneys have a preponderant role in IFN filtration, catabolism and excretion.

show abstract

Section: Discussionsupporting

confidence: 84%

Renal Metabolism of Rabbit Serum Interferon

Bocci

Pacini

Muscettola

et al. 1981

Journal of General Virology

Self Cite

View full text Add to dashboard Cite

show abstract

“…IFN ␤-1a has a molecular mass of ϳ25 kDa, and the kidney has been shown to be the major site of interferon degradation based on published animal studies, among which one study quantified the renal clearance contribution as more than 90% of total clearance in rats (Bino et al, 1982a,b;Bocci et al, 1984). The clearance pathway of interferon ␣ by the kidneys is described as an initial filtration, followed by absorption by the proximal tubular cells, and subsequent catabolism in cellular lysosomes (Bocci et al, 1981(Bocci et al, , 1984. Incorporation of a single 20-kDa PEG resulted in an increase in the apparent M r of the protein from ϳ25 to ϳ320 kDa as measured by size exclusion chromatography (Baker et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

In Vivo Pharmacology and Toxicology Evaluation of Polyethylene Glycol-Conjugated Interferon β-1a

Hu¹,

Olivier²,

Polack³

et al. 2011

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Human interferon (IFN) ␤ has well established beneficial effects in treating relapsing forms of multiple sclerosis, but current first-line treatment requires frequent (from daily to weekly) parenteral administration. A 20-kDa polyethylene glycol (PEG)-conjugated IFN ␤-1a (PEG-IFN ␤-1a) is being developed to decrease the frequency of administration and improve patient convenience and compliance. We present pharmacokinetic (PK) and pharmacodynamic (PD) parameters, immunogenicity, and safety of PEG-IFN ␤-1a in Rhesus monkeys in support of a phase 1 clinical trial. Two single-dose PK/PD studies and one 5-week repeat-dose toxicity study compliant with good laboratory practice were conducted. The PK of IFN ␤-1a and PEG-IFN ␤-1a were modeled with a two-compartment model, and the link between drug concentration and neopterin response (PD marker) was described with an indirect stimulatory model. PEG-IFN ␤-1ashowed greater exposure, longer half-life, lower clearance, and reduced volume of distribution than unmodified IFN ␤-1a. Consistent with the pharmacology of type I IFNs, PEG-IFN ␤-1a resulted in the elevation of neopterin concentration, a transient body temperature increase, and a reversible lymphocyte count decrease. As expected, neutralizing antibodies to PEG-IFN ␤-1a formed in almost all monkeys after 5 weeks of treatment, which resulted in significantly reduced drug exposure and abrogation of neopterin induction. There were no drug-related adverse effects at doses up to 100 g/kg (11 MIU/kg) given subcutaneously or intramuscularly once weekly for 5 weeks. The no-observed-adverse-effect level was determined to be 100 g/kg (11 MIU/kg), the highest dose tested.

show abstract

“…Using these procedures, we have carried out about 30 successful renal perfusions with minimal hemolysis and very rare microhe maturia; and we have been able to measure the renal filtration, absorption and catabo lism of interferon-a [26],…”

Section: Discussionmentioning

confidence: 99%

An Analysis of the Optimal Conditions for Perfusing an Isolated Rabbit Kidney with Homologous Blood

Pacini¹,

Bocci²

1983

Kidney Blood Press Res

Self Cite

View full text Add to dashboard Cite

Isolated rabbit kidneys were perfused in a closed-circuit system with a number of media such a Krebs-Henseleit bicarbonate buffer with albumin, homologous platelet-free plasma, serum and whole blood. All of these media were unsatisfactory. In contrast, fresh blood deprived of platelets, leukocytes, floating lipoproteins, microaggregates and micro-clots did not cause vasoconstriction of the isolated kidney. Renal blood flow, glomerular filtration rate, urinary flow and glucose, cations and renal water reabsorption were approximately normal.

show abstract

Renal Filtration, Absorption and Catabolism of Human Alpha Interferon

Cited by 48 publications

References 26 publications

Renal Metabolism of Rabbit Serum Interferon

Renal Metabolism of Rabbit Serum Interferon

In Vivo Pharmacology and Toxicology Evaluation of Polyethylene Glycol-Conjugated Interferon β-1a

An Analysis of the Optimal Conditions for Perfusing an Isolated Rabbit Kidney with Homologous Blood

Contact Info

Product

Resources

About