Kawalek J C, Fetterer R H
Veterinary Pharmacology/Toxicology Branch, FDA, Beltsville, MD 20705.
Am J Vet Res. 1990 Dec;51(12):2044-9.
A study was made to determine the effect of Haemonchus contortus parasitic infection in lambs on the clearance of several IV administered drugs. Clearance of sulfobromophthalein or sulfathiazole from the plasma of lambs was unaffected by infection with H contortus. Clearance of antipyrine was enhanced by the infection, and thiabendazole treatment did not alter this effect. Clearance of chloramphenicol (CAP), administered as the succinate ester (CAPS), was not changed by the infection, but it was increased after treatment with thiabendazole. Changes in the mean body residence time and initial plasma concentration of CAPS and CAP after treatment with thiabendazole indicate that hydrolysis of CAPS to CAP was reduced. High concentrations of CAPS apparently enhanced its own elimination directly rather than via the expected sequence involving hydrolysis, glucuronidation, and excretion of CAP-glucuronide. Enhanced clearance of antipyrine following infection of lambs with H contortus can be explained in at least 2 ways. First, it is possible that the lambs did not have mature amounts of hepatic drug metabolizing enzyme activity as reported by other investigators, which may be explained by breed differences or animal husbandry practices. Second, infection of lambs by H contortus may have triggered an inductive response in hepatic cytochrome P-450-mediated activities, which might result via a generalized enhancement in hepatic protein synthesis associated with the physiologic response to replace plasma proteins and other blood components lost through gastrointestinal hemorrhage caused by the active feeding of adult worms. Other phase-II reactions such as acetylation, glucuronidation, and glutathione-S-transferase apparently were not affected.
开展了一项研究，以确定捻转血矛线虫寄生感染羔羊对几种静脉给药药物清除率的影响。感染捻转血矛线虫未影响羔羊血浆中磺溴酞或磺胺噻唑的清除率。感染使安替比林的清除率提高，而噻苯达唑治疗未改变这种影响。以琥珀酸酯（CAPS）形式给药的氯霉素（CAP）的清除率未因感染而改变，但在噻苯达唑治疗后增加。噻苯达唑治疗后CAPS和CAP的平均体内驻留时间及初始血浆浓度的变化表明，CAPS向CAP的水解减少。高浓度的CAPS显然直接增强了其自身的消除，而非通过预期的涉及CAP水解、葡萄糖醛酸化及CAP - 葡萄糖醛酸排泄的过程。羔羊感染捻转血矛线虫后安替比林清除率提高至少有两种解释。其一，有可能羔羊没有如其他研究者所报道的成熟量的肝脏药物代谢酶活性，这可能由品种差异或饲养管理方式来解释。其二，捻转血矛线虫感染羔羊可能触发了肝脏细胞色素P - 450介导活性的诱导反应，这可能是由于与对因成虫活跃取食导致胃肠道出血而流失的血浆蛋白和其他血液成分进行生理补偿相关的肝脏蛋白质合成普遍增强所致。其他II相反应如乙酰化、葡萄糖醛酸化及谷胱甘肽 - S - 转移酶显然未受影响。
