Bauer L A, Black D J, Lill J S
Department of Pharmacy, School of Pharmacy, University of Washington, Seattle 98195-7630, USA.
Eur J Clin Pharmacol. 1998 Oct;54(8):621-5. doi: 10.1007/s002280050524.
Vancomycin hydrochloride dosing requirements in morbidly obese patients with normal renal function were computed to determine the dose of vancomycin necessary to achieve target steady-state peak and trough concentrations and compared with a normal weight population.
Morbidly obese patients [total body weight (TBW) 165 kg, ideal body weight (IBW) 63 kg] required 31.2 mg x kg(-1) x d(-1) TBW or 81.9 mg x kg(-1) x d(-1) IBW to achieve the target concentrations. Normal weight patients (TBW 68.6 kg) required 27.8 mg x kg(-1) x d(-1) to achieve the same concentrations. Because of altered kinetic parameters in the morbidly obese patients (obese: t1/2 = 3.3 h, V = 52 L, CL = 197 ml x min(-1); normal: t1/2=7.2 h, V=46 L, CL=77 ml x min(-1), 20 of 24 patients required q8h dosing (1938 mg q8h) compared with q12h dosing (954 mg q12h) in all normal weight patients in order to avoid trough concentrations that were too low for prolonged periods. There was a good correlation between TBW and CL, but only fair correlation between TBW and V.
Doses required to achieve desired vancomycin concentrations are similar in morbidly obese and normal weight patients when TBW is used as a dosing weight for the obese (approximately 30 mg x kg(-1) x d(-1)). Shorter dosage intervals may be needed when dosing morbidly obese patients so that steady-state trough concentrations remain above 5 microg x ml(-1) in this population. Because of the large amount of variation in required doses, vancomycin serum concentrations should be obtained in morbidly obese patients to ensure that adequate doses are being administered. Dosage requirements for morbidly obese patients with renal dysfunction require further study.
计算肾功能正常的病态肥胖患者的盐酸万古霉素给药需求量，以确定达到目标稳态峰浓度和谷浓度所需的万古霉素剂量，并与正常体重人群进行比较。
病态肥胖患者[总体重（TBW）165kg，理想体重（IBW）63kg]需要31.2mg·kg⁻¹·d⁻¹ TBW或81.9mg·kg⁻¹·d⁻¹ IBW才能达到目标浓度。正常体重患者（TBW 68.6kg）需要27.8mg·kg⁻¹·d⁻¹才能达到相同浓度。由于病态肥胖患者的动力学参数发生改变（肥胖患者：t1/2 = 3.3小时，V = 52L，CL = 197ml·min⁻¹；正常患者：t1/2 = 7.2小时，V = 46L，CL = 77ml·min⁻¹），24例患者中有20例需要每8小时给药一次（每8小时1938mg），而所有正常体重患者为每12小时给药一次（每12小时954mg），以避免谷浓度长时间过低。TBW与CL之间存在良好的相关性，但TBW与V之间只有中等相关性。
当将TBW用作肥胖患者的给药体重时（约30mg·kg⁻¹·d⁻¹），病态肥胖患者和正常体重患者达到所需万古霉素浓度所需的剂量相似。给病态肥胖患者给药时可能需要更短的给药间隔，以使该人群的稳态谷浓度保持在5μg·ml⁻¹以上。由于所需剂量差异很大，应测定病态肥胖患者的万古霉素血清浓度，以确保给予足够的剂量。肾功能不全的病态肥胖患者的给药需求量需要进一步研究。
