Martin G P, Loveday B E, Marriott C
Department of Pharmacy, King's College London, UK.
J Pharm Pharmacol. 1993 Feb;45(2):126-30. doi: 10.1111/j.2042-7158.1993.tb03696.x.
Three adult mini-pigs were employed to assess the effects of a twice daily dosage (40 mg kg-1) of oxytetracycline hydrochloride (OTC) and a combination of OTC with (0.5 mg kg-1) bromhexine hydrochloride (BHC) on the rheological properties and wet weight of secreted tracheal mucus. Mucus was collected daily from open-ended tracheal pouches established surgically in the mini-pigs. After a five day control period, either OTC or OTC plus BHC was administered twice daily with the normal diet. Each study period was followed by a five day washout period when mucus was collected but no drug given. The viscoelastic properties of each mucus sample were determined using creep compliance analysis. OTC was shown to increase the residual shear viscosity IP < 0.01) and increase the instantaneous compliance (P < 0.01). An increase in the wet weight of the collected mucus occurred in one pig only (P < 0.01). When BHC was co-administered with OTC, all of these changes were abolished. Evidence was obtained to suggest that BHC increased the concentration of OTC within the secreted mucus. BHC appeared to reverse the mucospissic activity of OTC in-vivo.
选用三只成年小型猪,评估每日两次剂量(40毫克/千克)的盐酸土霉素(OTC)以及OTC与(0.5毫克/千克)盐酸溴己新(BHC)联合使用对气管分泌黏液的流变学特性和湿重的影响。黏液每天从通过手术在小型猪身上建立的开放式气管袋中收集。在为期五天的对照期后,将OTC或OTC加BHC与正常饮食一起每日给药两次。每个研究期之后是为期五天的洗脱期,在此期间收集黏液但不给药。使用蠕变柔量分析确定每个黏液样品的粘弹性特性。结果显示,OTC可增加残余剪切粘度(P<0.01)并增加瞬时柔量(P<0.01)。仅在一只猪中观察到收集的黏液湿重增加(P<0.01)。当BHC与OTC联合给药时,所有这些变化均被消除。有证据表明,BHC可增加分泌黏液中OTC的浓度。BHC似乎在体内逆转了OTC的黏痰形成活性。