Intravenous and intramuscular pharmacokinetics of recombinant leukocyte a interferon

Bornemann, L. D.; Spiegel, Herbert E.; Dziewanowska, Zofia E.; Krown, Susan E.; Colburn, Wayne A.

doi:10.1007/bf00544369

Cited by 24 publications

(2 citation statements)

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“…Additionally, on the macro-scale, analysis of different routes of injections on IFN- α pharmacokinetic is addressed by statistical modelling (a.k.a mixed effect models) [60–63]. Moreover, two compartment PK/PD models on patient populations have been reported in the literature [36, 38, 64–66]. The multi-scale PBPK/PD model presented here is a unique example of linking a detailed cellular signalling model to a whole-body PBPK model using the case of therapeutic protein.…”

Section: Discussionmentioning

confidence: 99%

Quantitative systems pharmacology of interferon alpha administration: A multi-scale approach

et al. 2019

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The therapeutic effect of a drug is governed by its pharmacokinetics which determine the downstream pharmacodynamic response within the cellular network. A complete understanding of the drug-effect relationship therefore requires multi-scale models which integrate the properties of the different physiological scales. Computational modelling of these individual scales has been successfully established in the past. However, coupling of the scales remains challenging, although it will provide a unique possibility of mechanistic and holistic analyses of therapeutic outcomes for varied treatment scenarios. We present a methodology to combine whole-body physiologically-based pharmacokinetic (PBPK) models with mechanistic intracellular models of signal transduction in the liver for therapeutic proteins. To this end, we developed a whole-body distribution model of IFN- α in human and a detailed intracellular model of the JAK/STAT signalling cascade in hepatocytes and coupled them at the liver of the whole-body human model. This integrated model infers the time-resolved concentration of IFN- α arriving at the liver after intravenous injection while simultaneously estimates the effect of this dose on the intracellular signalling behaviour in the liver. In our multi-scale physiologically-based pharmacokinetic/pharmacodynamic (PBPK/PD) model, receptor saturation is seen at low doses, thus giving mechanistic insights into the pharmacodynamic (PD) response. This model suggests a fourfold lower intracellular response after administration of a typical IFN- α dose to an individual as compared to the experimentally observed responses in in vitro setups. In conclusion, this work highlights clear differences between the observed in vitro and in vivo drug effects and provides important suggestions for future model-based study design.

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Section: Discussionmentioning

confidence: 99%

Quantitative systems pharmacology of interferon alpha administration: A multi-scale approach

et al. 2019

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“…In order to elucidate the pharmacokinetic profiles of recombinant interferon-α, many studies have been performed in human or animals, such as the pharmacokinetic profile of Escherichia coli-derived human interferon type alpha in mice [24] , Recombinant Human Interferon Alpha2b Formulations in healthy human volunteers [25] , recombinant leukocyte A interferon in patients with disseminated cancer [26] , recombinant interferon alpha-C in patients with metastatic renal cell carcinoma [27] , recombinant human interferon-alpha I in African green monkeys [28] , recombinant alpha A interferon in African green monkeys [29] , human recombinant interferon (Re-IFN-alpha A) in cynomolgus monkeys [30] , recombinant leukocyte A interferon in beagle dogs [31] , recombinant human interferon-alpha 2C in rat and marmoset [32] , recombinant feline interferon in cats [33] , recombinant chicken interferon-α in broiler chickens [34] . However, till now, to the best of our knowledge, no information on the pharmacokinetic characteristics of rBoIFN-α has been reported in scientific literatures.…”

Section: Introductionmentioning

confidence: 99%

Sığırlarda Rekombinant Bovine İnterferon-alfa Üzerine Farmakokinetik Çalışmalar

Yu¹,

Zhao²,

Li³

et al. 2018

Kafkas Univ Vet Fak Derg

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In order to evaluate the pharmacokinetics of recombinant bovine interferon-alpha (rBoIFN-α) in cattle, which has potential for its antiviral and immunomodulatory activities, 12 animals of 6-month age were classified into 4 groups (n=3) to receive rBoIFN-α through IV, IM or SC routes at a dose of 5.0×10 3 IU/kg. Serum rBoIFN-α titer was evaluated using cytopathic effect (CPE) inhibition bioassay. Then, the standard pharmacokinetic parameters were calculated using the DAS (Drug and statistics) software. The concentrationtime profiles of serum rBoIFN-α following IM administration, SC administration and IV administration were characteristics of the 1-, 1-, and 2-compartment open models, respectively. After a single dose of IV administration, the drug rapidly dispersed and was rapidly eliminated from the body (T1/2α=0.15±0.02 h, T1/2=6.48±0.49 h). After IM and SC administrations, the drug is rapidly absorbed and slowly eliminated from the body (For IM administration, Tmax=6.12±0.32 h, T1/2=8.19±0.74 h) (For SC administration, Tmax=4.06±0.56 h, T1/2=7.29±0.55 h). The bioavailability of rBoIFN-α after IM administration is 53.74%, which is higher than the bioavailability of SC administration (27.96%). Therefore, the results showed that the drug administration effect can be preferably obtained following a single dose IM injection using the rBoIFN-α aqueous preparation. We hope that this study will provide valuable information for the clinical application of rBoIFN-α as an potential antiviral agent.

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Pharmacokinetics

Shibata¹,

Ito²,

Takada³

2010

Pharmaceutical Sciences Encyclopedia

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Recombinant DNA technology has produced many proteins and peptides drugs in large scale, and they are becoming increasingly important as therapeutic agents. The successful development of recombinant proteins depends on the proper characterization of their pharmacokinetics and an understanding of the relationship between drug exposure or dose and the pharmacological response. This article describes the pharmacokinetics of clinically important peptide/protein drugs, such as insulin, erythropoietin (EPO), granulocyte‐colony stimulating factor (G‐CSF), interferon, growth hormone, leuprolide, desmopressin, and antibodies in relation to their administration routes and formulations.

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Intravenous and intramuscular pharmacokinetics of recombinant leukocyte a interferon

Cited by 24 publications

References 1 publication

Quantitative systems pharmacology of interferon alpha administration: A multi-scale approach

Quantitative systems pharmacology of interferon alpha administration: A multi-scale approach

Sığırlarda Rekombinant Bovine İnterferon-alfa Üzerine Farmakokinetik Çalışmalar

Pharmacokinetics

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