Pharmacokinetic and pharmacodynamic optimisation of intravenous tobramycin dosing among children with cystic fibrosis

被引:20
作者
Sherwin, Catherine M. T. [1 ]
Zobell, Jeffery T. [2 ,3 ]
Stockmann, Chris [1 ,4 ]
McCrory, Bradley E. [5 ]
Wisdom, Millie [6 ]
Young, David C. [7 ,8 ]
Olson, Jared [1 ,2 ]
Ampofo, Krow [1 ]
Spigarelli, Michael G. [1 ,4 ]
机构
[1] Univ Utah, Sch Med, Dept Paediat, Salt Lake City, UT 84112 USA
[2] Intermt Primary Childrens Hosp, Salt Lake City, UT 84132 USA
[3] Intermt Cyst Fibrosis Paediat Ctr, Salt Lake City, UT 84132 USA
[4] Univ Utah, Coll Pharm, Dept Pharmacol & Toxicol, Salt Lake City, UT 84112 USA
[5] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA
[6] Phoenix Childrens Hosp, Phoenix, AZ 85006 USA
[7] Intermt Cyst Fibrosis Adult Ctr, Salt Lake City, UT 84132 USA
[8] Univ Utah, Dept Pharmacotherapy, Coll Pharm, Salt Lake City, UT 84112 USA
关键词
Pseudomonas aeruginosa; Aminoglycosides; Pharmacometrics; NONMEM; ONCE-DAILY TOBRAMYCIN; THRICE-DAILY TOBRAMYCIN; POPULATION PHARMACOKINETICS; PULMONARY EXACERBATIONS; AMINOGLYCOSIDE THERAPY; MODEL; ANTIBIOTICS; INFECTIONS; PNEUMONIA; EFFICACY;
D O I
10.1007/s10928-013-9348-7
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
This study aimed to characterize the pharmacokinetics of tobramycin administered one, two, or three times daily and to develop an optimal dosing scheme for children with cystic fibrosis. Therapeutic drug monitoring data were obtained from children hospitalized at three academic medical centres from 2006 to 2012. Population pharmacokinetic models were constructed using NONMEM 7.2. Model-based simulations were performed in Matlab R2012b to identify optimal dosing regimens using pharmacodynamic targets. The pharmacokinetic analysis involved 257 patients with a median age of 8.1 years (range 0.1-18.8). Clearance was estimated as 5.59 L/h and the volume of distribution was 18.90 L. Mean (+/- SD) maximum serum concentrations were highest among patients dosed once per day (24.1 +/- A 8.9 mu g/mL) and were lower among patients dosed two and three times per day (11.2 +/- A 1.4 and 8.1 +/- A 2.4 mu g/mL, respectively). Simulations revealed that once daily dosing was the only effective regimen for a Pseudomonas aeruginosa MIC of 1.5 mu g/mL and none of the tested regimens reliably achieved the pharmacodynamic target for MICs a parts per thousand yen2 mu g/mL. Once daily dosing resulted in higher maximum serum concentrations when compared to multiple-daily dosing. In simulations, once daily dosing was the only regimen to achieve the pharmacodynamic target for all subjects with MICs < 2 mu g/mL.
引用
收藏
页码:71 / 79
页数:9
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