不同水温和给药方式下磺胺甲噁唑在草鱼体内的药动学研究
A STUDY ON PHARMACOKINETIC OF SULPHAMETHOXAZOLE IN GRASS CARP AT DIFFERENT TEMPERATURES AND ADMINISTRATION REGIMES
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摘要: 在18℃和28℃的不同水温条件下，分别采用口灌和腹腔注射的给药方式，给予草鱼100mg/kg体重单剂量的磺胺甲唑(SMZ)，以HPLC法测定草鱼血浆和肌肉中药物浓度，用MCPKP药代动力学软件处理药时数据，结果表明，18℃条件下，草鱼口灌SMZ的分布半衰期T1/2α、消除半衰期T1/2β、达峰时间Tp均显著长于28℃(P<；0.01)，其峰浓度Cmax显著低于28℃下的值(P<；0.01)；腹腔注射给药时，SMZ在鱼体血浆和肌肉中的吸收与分布较口服快，消除较口服也快。在水温18℃条件下，口灌SMZ在草鱼血浆中的药时数据符合带时滞的二室开放模型，腹腔注射的符合无时滞二室开放模型；水温28℃条件下，口灌SMZ在草鱼血浆中的药时数据符合可忽略时滞的二室开放模型。根据SMZ的药代动力学规律、最低有效血药浓度和抗菌药物应用的一般原则，制定了SMZ的用药方案：治疗温水性鱼类细菌性疾病，在水温18℃左右，口服或注射100mg/kg剂量的SMZ，以每天给药两次，3d一个疗程为宜；在水温28℃左右，以每天给药3-4次为宜。该项研究全面了解了在不同水温和不同给药方式下SMZ在鱼体内的药动学规律，为确定合理的临床用药方案以及无公害水产品中药物残留监测提供了可靠的理论依据。Abstract: At water temperature of 18℃ or 28℃,grass carp was administered orally or by intraperitoneal injection with sulphamethoxazole (SMZ) in single dose of 100mg/kg. The concentration of SMZ in the plasma and muscles of the fish were determined by high performance liquid chromatography and the concentration-time data were treated with MPKP practical pharmacokinetic software. The results showed that the elimination half-time (T 1/2α ),the elimination half-time (T 1/2β ) and the peak time of SMZ at oral administration at lower temperature were remarkably longer than those at higher temperature (P0.01). The peak concentration at lower temperature was significantly lower than that at higher temperature (P0.01). Absorption and elimination of SMZ in the plasma and muscle were quicker when administered by intraperitoneal injection than those when administered orally. and its elimination was quicker by intraperitoneal injection than at oral administration. At the temperature of 18℃,the profile of SMZ in the plasma could be described by a two-compartment open model with lag-time when administered orally. It could be described by a two-compartment model without lag-time when administered by intraperitoneal injection. At the temperature of 28℃,the profile could be described by a two-compartment open model with an illegible lag-time. Based on the pharmacokinetics of SMZ,the minimum effective blood drug concentration and the general principle in application of antibiotics,SMZ administration for grass carp is recommended to be in a 3 days treatment administered orally or by intraperitoneal injection twice a day,at 18℃ or 3-4 times a day at 28℃ at 100mg/kg.
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Keywords:
- Sulphamethoxazole /
- Grass carp /
- Pharmacokinetic /
- Water temperature /
- Administration regimes
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