Journal of pharmaceutical sciences
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The University of British Columbia (UBC) became the first university in Canada to develop a strategy for enhancing global access to its technologies. UBC's University-Industry Liaison Office, in collaboration with the UBC chapter of Universities Allied for Essential Medicines (UAEM), established a mandate and developed principles that provide the developing world with access to UBC technologies. This commentary will discuss these principles and provide examples of where they have been applied to several UBC technologies.
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It has been shown previously that it is impossible to measure the volume of distribution at steady state conclusively for a multicompartment system from an iv bolus dose only. The problem lies in deciding from which compartment elimination of the drug occurs in the compartmental model. ⋯ The two models examined predict different profiles in the absorption phase of an oral profile. An in vivo data set is provided that favours a peripheral elimination explanation of its observed pharmacokinetics, based on the 'goodness of fit'.
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WST11, a novel generation of photo sensitizers to be used for vascular-targeted phototherapy (VTP), is effective at short interval between injection and illumination and it is expected to enable selective destruction of neovasculature with minimal side effects or skin photo toxicity. This study was conducted to evaluate the clinical and laboratory safety, tolerability and pharmacokinetic profile of WST11 given as a single intravenous administration (1.25, 2.5, 5, 7.5, 10, or 15 mg/kg) during an escalating dose study in healthy male subjects. This article describes WST11 population pharmacokinetic modeling and simulations performed to optimize the IV infusion-dosing regimen in combination with illumination, the target PK profile being plateau concentrations during approximately 30 min. ⋯ The study results do not indicate that the dose should be adjusted for body size. The only factor that determines the drug input profile is the dose level, since the elimination half-life decreases when the dose administered increases. The use of the population PK model for simulations has shown that, at dose level of 5 mg/kg or more, a loading dose of 80% dose given over 5 min followed by 15% of dose during 10 min and remained dose to give over 10 min would result in a favorable PK profile.
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IVIG may achieve its beneficial effects in immune thrombocytopenia (ITP) patients via several mechanisms; however, little is known of the relative importance of various mechanisms associated with IVIG action in ITP. The purposes of this study were to develop a pharmacokinetic/pharmacodynamic (PK/PD) model relating an anti-platelet antibody, MWReg30, to platelet counts in a mouse model of sustained ITP, to use modeling to characterize effects of IVIG on MWReg30 elimination, and to use PK/PD modeling to assess the contribution of IVIG effects on MWReg30 disposition to the effects of IVIG on MWReg30-induced thrombocytopenia in mice. A pharmacokinetic model, based on the competitive occupancy of protective FcRn receptors, was used to characterize the effects of IVIG on MWReg30 pharmacokinetics. ⋯ The pharmacokinetic model well-captured MWReg30 plasma concentration-time profiles, with and without administration of IVIG. The indirect response model accurately characterized the effects of IVIG on MWReg30-induced thrombocytopenia in mice. Using these models, it was estimated that 43 +/- 5% of overall effects of IVIG on MWReg30-induced thrombocytopenia in mice could be accounted for by the IVIG-mediated increases in MWReg30 clearance.
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The aim of this work was to study the characteristics of powders of morphine HCl suitable for nasal administration to be employed for pain treatment as alternative to injection. Primary microparticles of morphine were prepared by spray drying of aqueous drug solutions using sugars or sugar derivatives as drying protectors and particle shapers. The spray drying procedure modified morphine crystallinity making the substance amorphous and affecting its stability in dependence on the excipient employed. ⋯ Lactose was the most effective excipient for agglomerate manufacturing and delivery of spray-dried morphine. The agglomerates of morphine crystals mixed with mannitol/lecithin microparticles showed superior stability. However, the drug permeation through rabbit mucosa was slower than with spray-dried morphine microparticle agglomerates.