AbstractOne of the major limiting steps for the absorption of peptide drugs from the intestine is proteolytic degradation. To slow this degradation, human calcitonin was trapped in polyacrylamide nanoparticles, and human calcitonin and insulin were encapsulated with polyisobutylcyanoacrylate. Human calcitonin trapped in polyacrylamide nanoparticles showed no delayed release characteristics and thus would not provide protection from proteases. Proteolytic degradation of human calcitonin and insulin in polyisobutylcyanoacrylate nanocapsules was slower than the free peptides in solution. The plasma pharmacokinetic profiles were consistent with increased survival time of the peptides in the intestine, with higher plasma concentrations of the peptides in the later time samples compared with the controls. However, the nanocapsules gave no significant overall enhancement of peptide absorption. This led to the conclusion that the nanocapsules released the peptides into the intestinal lumen, with small amounts then being absorbed but the rest largely degraded.

12 Apr 2011·Journal of Pharmacy and PharmacologyQ3 · MEDICINE

The Transmucosal Absorption of Recombinant Human Interferon-α B/D Hybrid in the Rat and Rabbit

Q3 · MEDICINE

Article

Author: Clay, Val ; Temple, Cathy ; Lowther, Nicholas ; Bayley, Deborah ; Steward, Alan

AbstractFor therapeutic proteins such as interferon-α B/D, a non-parenteral route of delivery is desirable. Possible sites of administration include the various regions of the gastrointestinal tract and airways, and this paper reports the bioavailability of interferon-α B/D via these routes in the rat and rabbit.Apart from the stomach, detectable levels of interferon-α B/D in the serum were achieved via all routes. Bioavailabilities were less than 1%, except from the lung (6·8% in the rat) and nasal cavity (2·9% in the rabbit). Absorption from the gastrointestinal tract was similar for both species, but in the nasal cavity of the rabbit was sixfold that of the rat, and in the lung of the rat was tenfold that in the rabbit. Absorption from all routes, except the buccal cavity, resulted in detectable biochemical changes in the liver of the rabbit.Comparison with reports from other groups show differences in the extent of absorption of interferon-α B/D and of natural or homologous recombinant interferon-α. The non-parenteral delivery of biochemically active amounts of interferon-α B/D is thus demonstrated.

01 Jan 1997·Thrombosis and HaemostasisQ2 · MEDICINE

Effect of a 15-Minute Infusion of DDAVP on the Pharmacokinetics and Pharmacodynamics of ™REVASC during a Four-Hour Intravenous Infusion in Healthy Male Volunteers

Q2 · MEDICINE

Article

Author: Amin, Dipti M ; Mant, Timothy G K ; Close, Philippe ; Kerry, Roger ; Lefèvre, Gilbert ; Walker, Stephen M ; Lloyd, Peter

SummaryPlasma pharmacokinetics, effect on coagulation parameters, and safety and tolerability of an intravenous infusion of ™REVASC before, during and after a DDAVP infusion were investigated.Twelve healthy volunteers were given an intravenous bolus dose followed by a constant rate four-hour infusion of ™REVASC. Fifteen-minute infusions of 0.9% saline and DDAVP were started two and three hours respectively after the start of the ™REVASC infusion.Plasma ™REVASC concentrations were not affected by either the saline or DDAVP infusion. ™REVASC infusion produced an increase in APTT which plateaued between 0.5 and 3 hours. After the DDAVP infusion there was a tendency towards a new lower plateau whilst the ™REVASC infusion continued. There were no serious adverse events or bleeding episodes throughout the study.In conclusion, the co-administration of intravenous DDAVP has no effect on the plasma pharmacokinetics of ™REVASC and partially reverses the ™REVASC-induced increase in APTT. This may represent a role for DDAVP in the partial reversal of anticoagulation induced by ™REVASC.

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