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庆大霉素剂量需求:242例肾功能正常的手术患者之间存在广泛的个体差异。

Gentamicin dosage requirements: wide interpatient variations in 242 surgery patients with normal renal function.

作者信息

Zaske D E, Cipolle R J, Strate R J

出版信息

Surgery. 1980 Feb;87(2):164-9.

PMID:7355388
Abstract

Wide interpatient variations were demonstrated in gentamicin elimination rate and dosage requirements for 242 surgery patients with normal renal function. These patients' half-lives ranged from 0.4 to 13.4 hours as compared to previous reports of 2.5 to 4 hours. The distribution volumes ranged from 0.06 to 0.63 liter/kg, as compared of reported values of 0.20 to 0.25 liter/kg. These wide interpatient variations in kinetic parameters, combined with the need to obtain narrow ranges in serum concentrations, necessitated measuring serum concentrations and individually calculating each patient's dosage regimen early in the treatment course. Using this approach, optimal peak and trough serum levels were consistently produced in these patients. Their required dosage regimens demonstrated considerable variability--ranging from 0.7 to 12.4 mg/kg/day. Compared to the recommended regimen (3 to 5 mg/kg/day), 47% of these surgery patients required higher dosages, and 14% required lower dosages. The incidence of ototoxicity and nephrotoxicity were extremely low, with only three patients possibly having gentamicin-associated nephrotoxicity. These results further emphasize the need to measure serum concentrations and make necessary dosage adjustments to ensure therapeutic levels. However, because of the wide interpatient variation, these increased dosage regimens are not routinely suggested without previously measuring serum concentrations.

摘要

242例肾功能正常的外科手术患者在庆大霉素清除率和剂量需求方面存在较大的个体差异。这些患者的半衰期为0.4至13.4小时,而之前报道的半衰期为2.5至4小时。分布容积为0.06至0.63升/千克,而报道的值为0.20至0.25升/千克。动力学参数的这些广泛个体差异,加上需要使血清浓度保持在较窄范围内,使得在治疗过程早期有必要测量血清浓度并单独计算每位患者的给药方案。采用这种方法,这些患者始终能产生最佳的血清峰浓度和谷浓度。他们所需的给药方案显示出相当大的变异性,范围为0.7至12.4毫克/千克/天。与推荐方案(3至5毫克/千克/天)相比,这些外科手术患者中有47%需要更高的剂量,14%需要更低的剂量。耳毒性和肾毒性的发生率极低,只有三名患者可能出现与庆大霉素相关的肾毒性。这些结果进一步强调了测量血清浓度并进行必要剂量调整以确保达到治疗水平的必要性。然而,由于个体差异较大,在未预先测量血清浓度的情况下,通常不建议增加给药方案。

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