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  • Title: Influence of absorption enhancers on the pharmacokinetic properties of non-oral beta-lactam-cefpirom using the rabbit (Chinchilla) in vivo model.
    Author: Mrestani Y, Härtl A, Neubert RH.
    Journal: Int J Pharm; 2006 Feb 17; 309(1-2):67-70. PubMed ID: 16377108.
    Abstract:
    The oral application is the application of the first choice for drug administration. A lot of drugs exhibit relatively low bioavailability. This may be caused by binding of the drug in the gastro-intestinal tract, by poor penetration of the intestinal mucose or by highly hydrophilic properties. Therefore, problem drugs were only used for i.v. administration (intravenously) or for i.m. administration (intramuscularly). In the present study, cefpirom was investigated as a model substance. Cefpirom (Cp) is a semi-synthetic amino-2-thiazolyl-methoxyimino cephalosporin. It exhibits highly hydrophilic properties (P(ow)=0.02+/-0.01) and a very low bioavailability (AUC=524+/-403 microg min/ml). It was only applied i.v. or i.m. In this work, the influence of absorption enhancers (aggregation and ion-pair formation) on the bioavailability and on the hydrophilic properties of Cp was investigated. The bioavailability of cefpirom was improved through the combination with absorption enhancers (hexadecyldimethylbenzylammonium chloride, BAC; hexylsalicylic acid, HSA). The absolute bioavailability of the Cp combination with absorption enhancers was 21 times larger for BAC and 15 times larger for HSA than in the case when Cp was used alone.
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