抗微生物药物在山羊体内独特的药动学和药效学参数

S. Saganuwan
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引用次数: 6

摘要

药代动力学是涉及抗菌剂的药物吸收、分布、代谢和排泄(ADME)的过程,它决定了药效学反应,即药物对身体的作用。因此,在所有药代动力学参数中,消除半衰期(t1 / 2 β)、分布体积(Vd)、最大血药浓度(Cmax)和最大到达时间(Tmax)是最重要的参数。因此,这些参数在确定抗菌素的药代动力学和药效学反应方面是独一无二的。然而,它是消除半衰期和最低抑制浓度(MIC)决定给药间隔的抗菌素。庆大霉素在2.5 mg/kg的剂量范围内通过4 mg/kg(环丙沙星)、4.2 mg/kg(氨苄西林L/A)、5 mg/kg(卡那霉素、恩诺沙星、加替沙星、诺氟沙星)、7 mg/kg(甲喹诺多)、10 mg/kg(阿米卡星、恩诺沙星、林可霉素、培氟沙星、头孢匹罗、红霉素、异烟肼)、20 mg/kg(土霉素)、30 mg/kg(甲硝唑),消除半衰期为1.2 ~ 67.2 h, Cmax为0.12 ~ 54.4 μ g/ml, Tmax为0.2 ~ 24 h。肌肉、静脉和口服给药时生物利用度为16 - 99.8%,血浆蛋白结合率为0 - >80%。人等效剂量公式可用于推断人-羊抗微生物药物的治疗剂量。然而,磺胺嘧啶、土拉霉素、土霉素、阿奇霉素等抗菌素在乳汁、肾脏、肝脏、肠道、大脑和骨骼肌中的残留量可能很高,可能是抗菌素耐药、过敏反应、表皮坏死松解、史蒂文斯-约翰逊综合征等药物不良反应的高风险。
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Unique Pharmacokinetic and Pharmacodynamic Parameters of Antimicrobials in Goats
Pharmacokinetics, the process that involves drug absorption, distribution, metabolism and excretion (ADME) of antimicrobials, determines pharmacodynamic response, that is, what drugs do to the body. Therefore, of all the pharmacokinetic parameters, elimination half-life (T 1 / 2 β ), volume of distribution (Vd), maximum plasma concentration (Cmax) and maximum time reached (Tmax) are the most important parameters. Hence, the parameters are unique in determining pharmacokinetic and pharmacodynamic response of antimicrobials. However, it is elimination half-life and minimum inhibitory concentration (MIC) that determine the dosing interval of antimicrobials. The dose range of 2.5 mg/kg for gentamicin passing through 4 mg/kg (ciprofloxacin), 4.2 mg/kg (ampicillin L/A), 5 mg/kg (kanamycin, enrofloxacin, gatifloxacin and norfloxacin), 7 mg/kg (mequindox), 10 mg/kg (amikacin, enrofloxacin, lincomycin, pefloxacin, cefpirome, erythromycin and isoniazid), 20 mg/kg (oxytetracycline) and 30 mg/kg (metronidazole) have elimination half-life of 1.2 – 67.2 h, Cmax of 0.12 – 54.4 μ g/ml, Tmax of 0.2 – 24 h, bioavailability of 16 – 99.8% and plasma protein binding of 0 – >80% when administered intramuscularly, intravenously and orally. Human equivalent dose formula could be used to extrapolate human-goat therapeutic doses of antimicrobials. How-ever, some antimicrobials such as sulfadimidine, tulathromycin, oxytetracycline and azithromycin may have high residues in the milk, kidneys, liver, intestines, brain and skeletal muscles and may portend high risk of antimicrobial resistance, hypersensitivity reaction, epidermal necrolysis, Stevens-Johnson syndrome and other adverse drug reactions.
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