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  1. Overcoming barriers to optimal drug dosing during ECMO in critically ill adult patients
    Cheng V, Abdul-Aziz MH, Roberts JA, Shekar K
    Expert Opin Drug Metab Toxicol, 2019 Feb;15(2):103-112.
    PMID: 30582435 DOI: 10.1080/17425255.2019.1563596
    INTRODUCTION: One major challenge to achieving optimal patient outcome in extracorporeal membrane oxygenation (ECMO) is the development of effective dosing strategies in this critically ill patient population. Suboptimal drug dosing impacts on patient outcome as patients on ECMO often require reversal of the underlying pathology with effective pharmacotherapy in order to be liberated of the life-support device. Areas covered: This article provides a concise review of the effective use of antibiotics, analgesics, and sedative by characterizing the specific changes in PK secondary to the introduction of the ECMO support. We also discuss the barriers to achieving optimal pharmacotherapy in patients on ECMO and also the current and potential research that can be undertaken to address these clinical challenges. Expert opinion: Decreased bioavailability due to sequestration of drugs in the ECMO circuit and ECMO induced PK alterations are both significant barriers to optimal drug dosing. Evidence-based drug choices may minimize sequestration in the circuit and would enable safety and efficacy to be maintained. More work to characterize ECMO related pharmacodynamic alterations such as effects of ECMO on hepatic cytochrome system are still needed. Novel techniques to increase target site concentrations should also be explored.
    Matched MeSH terms: Analgesics/pharmacokinetics
  2. Fulltext Topical piroxicam in vitro release and in vivo anti-inflammatory and analgesic effects from palm oil esters-based nanocream
    Abdulkarim MF, Abdullah GZ, Chitneni M, Salman IM, Ameer OZ, Yam MF, et al.
    Int J Nanomedicine, 2010 Nov 04;5:915-24.
    PMID: 21116332 DOI: 10.2147/IJN.S13305
    INTRODUCTION: During recent years, there has been growing interest in use of topical vehicle systems to assist in drug permeation through the skin. Drugs of interest are usually those that are problematic when given orally, such as piroxicam, a highly effective anti-inflammatory, anti-pyretic, and analgesic, but with the adverse effect of causing gastrointestinal ulcers. The present study investigated the in vitro and in vivo pharmacodynamic activity of a newly synthesized palm oil esters (POEs)-based nanocream containing piroxicam for topical delivery.

    METHODS: A ratio of 25:37:38 of POEs: external phase: surfactants (Tween 80:Span 20, in a ratio 80:20), respectively was selected as the basic composition for the production of a nanocream with ideal properties. Various nanocreams were prepared using phosphate-buffered saline as the external phase at three different pH values. The abilities of these formulae to deliver piroxicam were assessed in vitro using a Franz diffusion cell fitted with a cellulose acetate membrane and full thickness rat skin. These formulae were also evaluated in vivo by comparing their anti-inflammatory and analgesic activities with those of the currently marketed gel.

    RESULTS: After eight hours, nearly 100% of drug was transferred through the artificial membrane from the prepared formula F3 (phosphate-buffered saline at pH 7.4 as the external phase) and the marketed gel. The steady-state flux through rat skin of all formulae tested was higher than that of the marketed gel. Pharmacodynamically, nanocream formula F3 exhibited the highest anti- inflammatory and analgesic effects as compared with the other formulae.

    CONCLUSION: The nanocream containing the newly synthesized POEs was successful for trans-dermal delivery of piroxicam.

    Matched MeSH terms: Analgesics/pharmacokinetics
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