International journal of pharmaceutics
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A wet-primed ready-to-use extracorporeal membrane oxygenation (ECMO) circuit is used in some centres for rapid deployment of ECMO during cardiopulmonary resuscitation. Yet, the potential release of plasticizer di(2-ethylhexyl)phthalate (DEHP) from the polyvinyl chloride tubing in the circuit during storage is a concern. ⋯ No accumulation of DEHP in the circulating fluid was detected. The results provide important information for centres where ECMO circuits are kept wet-primed prior to clinical use.
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This study evaluated the effects of combined use of two nonionic surfactants on the characteristics (i.e., appearance, emulsification time, and particle size) of oil-in-water microemulsions generated from flurbiprofen-loaded preconcentrates. ⋯ The combined use of surfactants in preconcentrate showed the promise in generating desired self-emulsifying microemulsions with small particle size, increased drug loading, and improved physical stability. This will have significant implications in future dosage development for poorly water-soluble drugs in using self-emulsifying microemulsions drug delivery system (SMEDDS).
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The pharmacokinetics of total and free plasma platinum (Pt) and Pt tissue distribution were investigated in rats after oral administration of (OC-6-43)-bis(acetato)(1-adamantylamine)amminedichloroplatinum(IV) (LA-12). Plasma and ultrafiltrate were sampled until 48 h and tissue samples were taken at 24 and 48 h after single doses of 38.6 or 540 mg LA-12/kg, and after once-a-day dosing of 4.3 or 38.6 mg kg(-1) LA-12 over 14 consecutive days. Total plasma Pt concentrations increased less than proportionally to the 14-fold increase in the single dose. ⋯ After once-a-day dosing, tissue Pt levels increased proportionally with the dose within the range from 4.3 to 38.6 mg kg(-1). At the same time, the increase in total plasma Pt concentrations was 40% less than proportional. Concentrations of Pt in the plasma ultrafiltrate decreased rapidly with the initial half-life of 1 h.
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Comparative Study
Enhanced paclitaxel bioavailability after oral administration of pegylated paclitaxel prodrug for oral delivery in rats.
The bioavailability and pharmacokinetic parameters of paclitaxel in a PEGylated paclitaxel prodrug were studied after the oral administration of paclitaxel (25, 50, 100 mg/kg) and prodrug (87.5, 175, 350 mg/kg) in rats. The area under the plasma concentration-time curve (AUC) of paclitaxel by oral paclitaxel were 836, 1,602 and 3,076 ng/mlh, which increased dose-dependently (P < 0.006, r = 0.9996). The AUCs of paclitaxel by the oral paclitaxel prodrug were 1,646, 3,079 and 5,998 ng/mlh, also increased dose-dependently (P < 0.003, r = 0.9999). ⋯ At the same dose of paclitaxel, the AUC of paclitaxel in the prodrug resulted in a remarkable increase, approximately four-fold compared to the oral paclitaxel. It might be considered that the significantly enhanced bioavailability of paclitaxel by the prodrug, which is water-soluble and easy to permeat through the intestinal mucosa, is due to the avoidance of being inhibited by p-glycoprotein efflux pump in the intestinal mucosa and reduction of metabolism by cytochrome-p-450 (CYP3A) in epitherial cells of small intestine. It appears that the development of oral paclitaxel preparations as a prodrug is possible, which will be more convenient than the IV dosage form.
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The aim of this study was to evaluate the potential of using three new aqueous formulations of propofol for intravenous (i.v.) anesthesia. The first formulation can be prepared by using hydroxypropyl-gamma-cyclodextrin (HP-gamma-CD) as a solubilizer. Phase-solubility analysis showed a linear increase in the solubility of propofol to a maximum of 16.6 mg/ml in 30% (w/v) HP-gamma-CD. ⋯ The efficacy of all these formulations as i.v. anesthetic agents was assessed using a pharmacodynamic measure (onset and duration of loss of the righting reflex, LORR), and compared with that of the commercial propofol formulation (Diprivan, 10 mg/ml) in rats. It was found that minimizing the amount of cyclodextrin in all CD-based formulations, anesthetic effects comparable to those of propofol in Diprivan were still observed. Moreover, the prolinate ester constituted an effective i.v. anesthetic formulation with the same duration of action but with a longer induction time than Diprivan.