Evaluation of Bayesian predictability of vancomycin concentration using population pharmacokinetic parameters in pediatric patients

The objective of this study was to evaluate the Bayesian predictability of vancomycin (VCM) pharmacokinetics in Japanese pediatric patients using one-compartment population pharmacokinetic (PPK) parameters, which we reported previously. The validity of the PPK model was evaluated by bootstrap method and cross validation method, and the Bayesian predictive performance was examined. The predictive performance of the PPK model for premature patients was also examined. The cross validation method showed the predictability to be acceptable for practical use, especially for predicting trough concentration using other trough data. However, for the external premature patient data, this PPK model did not seem to be adequate. A theoretical approach using a simulation technique was also examined to evaluate the predictive performance. The results suggested that the predictability at the peak was not necessarily good at all sampling times and the predictability at the trough was better when a later time point was used. The optimal sampling time for prediction of VCM concentration in pediatric patients is discussed.     

Disposition of minoxidil in patients with various degrees of renal function

The disposition of minoxidil was evaluated after a 5 mg oral dose in 24 subjects with various degrees of renal function. Patients were divided into four groups based on a 24-hour ambulatory creatinine clearance (Clcr): Group I (n = 6) Clcr greater than 90 mL/min, Group II (n = 6) Clcr 50-80 mL/min, Group III (n = 5) Clcr of 30-49 mL/min, and Group IV (n = 7) Clcr less than 30 mL/min. Blood and urine samples obtained over 36 hours were analyzed for minoxidil by a high pressure liquid chromatography technique. Maximum plasma concentration (Cmax) and time to reach Cmax did not differ among the four groups. The terminal elimination half-life was prolonged in Group IV subjects (8.87 +/- 6.12 hours) (mean +/- SD) compared to those in Groups I, II and III (1.38 +/- 0.16, 1.99 +/- 0.45 and 2.42 +/- 0.53 hours, respectively). Apparent total body clearance (Clp/F) decreased as renal function declined; Clp/F = 0.82(Clcr) + 21.8, r = 0.739, P = 0.0001. Renal clearance and apparent nonrenal clearance also were significantly correlated with Clcr. The apparent volume of distribution significantly increased as renal function declined. Thus, the disposition of minoxidil is significantly delayed and dosage adjustment may be necessary in patients with renal insufficiency.     

Bayesian estimation of pharmacokinetic parameters of vancomycin in patients with decreasing renal function

In clinical settings, decrease of renal function is frequently observed in patients treated with vancomycin (VCM). In this study, mutable covariates models (MCMs) were constructed to analyze the pharmacokinetics (PK) of VCM with Bayesian estimation, considering time-dependent decreases in creatinine clearance in 23 patients with decreasing renal function. The predicted mean percentage error (MPE) of VCM concentrations analyzed with a conventional fixed covariates model (FCM) was -19.1%, whereas the MPE was improved to 2.5% by applying MCM. Furthermore, a probable lag time between fluctuations in VCM clearance (CL(VCM) ) and serum creatinine (S(cr) ) was analyzed by MCM, MCM(Lag1d) , and MCM(Lag2d) , which considered lag times of 0, 1, and 2 days, respectively. Compared with FCM, all MCMs improved fitness with the significantly decreased root mean square percentage error (RMSPE) and MPE. However, RMSPE and MPE analyzed with MCM were not significantly different from those with MCM(Lag1d) and MCM(Lag2d) , indicating that lag times between alterations in CL(VCM) and S(cr) were obscure in these patients. Collectively, these results suggest that PK parameters of VCM were more accurately calculated by MCMs than by conventional FCM, and that VCM dosages calculated by FCM would be overestimated by approximately 20% in patients with decreasing renal function.     

万古霉素治疗101例重症感染儿童患者的血药浓度与肾功能损伤评价

目的探讨重症感染儿童患者万古霉素血药浓度与肾损伤的关系,为减少药物不良反应、促进临床合理用药提供参考。方法采用回顾性分析方法,收集我院2010年5月—2015年5月101例重症感染患儿病历信息和万古霉素血药浓度数据,分析万古霉素血药浓度变化与肌酐和尿素氮、胱抑素C、清除率的关系。结果万古霉素血药浓度>20μg·m L~(-1)患儿的治愈率与血药浓度<10μg·mL~(-1)的患儿相比有增高趋势(94%vs.85%,P=0.052)。其中,22例重症感染患儿在万古霉素治疗前后血肌酐和尿素氮水平均在正常范围内,但胱抑素C水平[(1.76±0.33)mg·L~(-1)]明显高于正常范围(0.51～1.09 mg·L~(-1))。重症感染的新生患儿(年龄<28 d)万古霉素的清除率明显低于非新生患儿[(2.94±3.70)vs.(4.09±3.58)m L·mim~(-1)·kg~(-1),P<0.05]。但不同性别儿童患者的清除率无显著差异(P>0.05)。结论常规监测重症感染患儿万古霉素血药浓度和肾功能,给药个体化,能减轻早期肾损伤。     

The pharmacokinetics of remoxipride and metabolites in patients with various degrees of renal function.

1. The pharmacokinetics of remoxipride, a new neuroleptic, were investigated in an open study with three parallel groups. Twenty-one patients with severely impaired (ClCr < 25 ml min-1), moderately impaired (ClCr 25-50 ml min-1) and normal (ClCr > 65 ml min-1) renal function were evaluated. A single oral dose of remoxipride hydrochloride 100 mg was administered, and blood and urine were collected over 48 h. Concentrations of remoxipride and metabolites were measured by h.p.l.c. 2. In patients with severely decreased renal function, the AUC and Cmax of remoxipride were increased significantly, and t1/2 was prolonged, as compared with the control patients. The renal clearance and urinary recovery of the unchanged drug were significantly diminished. 3. The unbound fraction of remoxipride in plasma was decreased in patients with renal failure, in association with a disease-related increase in alpha 1-acid glycoprotein. In spite of a 25% recovery of unchanged drug in the urine in patients with normal renal function, the AUC of unbound drug was twice as high in patients with severely impaired renal function. 4. A strong correlation between creatinine clearance and renal drug clearance was observed indicating a direct relationship between kidney function and the renal clearance of remoxipride. 5. Remoxipride was the predominant compound in plasma as well as in urine in patients with severely decreased as well as normal renal function. In patients with severely decrease renal function, remoxipride and all five pharmacologically inactive metabolites showed increased peak plasma concentrations, delayed tmax, increased AUC, prolonged half-lives and decreased renal clearance.     

Gentamicin disposition in young and elderly patients with various degrees of renal function

The effect of aging on the total body clearance, volume of distribution, and half-life of gentamicin was examined in 99 febrile patients with various degrees of renal function. In the 50 patients who were 18 to 64 years old, clearance of gentamicin was 79.0 +/- 27.0 mL/min (mean +/- standard deviation), creatinine clearance was 98.6 +/- 33.3 mL/min, volume of distribution was 0.242 +/- 0.077 L/kg, and half-life was 2.63 +/- 0.90 hours. In the 49 patients who were 65 to 90 years old, these values were 36.9 +/- 16.3 mL/min, 51.2 +/- 21.2 mL/min, 0.244 +/- 0.102 L/kg, and 5.80 +/- 4.13 hours. Significant differences were observed between the two groups for all parameters except volume of distribution. Linear regression revealed good correlations between the disposition characteristics (clearance and elimination-rate constant) of gentamicin and age as well as creatinine clearance. However, there was no apparent relationship between the ratio of gentamicin clearance to creatinine clearance and age (r = .0731). These findings suggest that the disposition of gentamicin is independent of age but dependent on renal function.     

Tigecycline pharmacokinetics in subjects with various degrees of renal function

The pharmacokinetic parameters of tigecycline were assessed in subjects with severe renal impairment (creatinine clearance <30 mL/min, n = 6), subjects receiving hemodialysis (4 received tigecycline before and 4 received tigecycline after hemodialysis), and subjects with age-adjusted, normal renal function (n = 6) after administration of single 100-mg doses. Serial serum and urine samples were collected and assayed using validated liquid chromatography with tandem mass spectrometer (LC/MS/MS) methods. Concentration-time data were then analyzed using noncompartmental pharmacokinetic methods. Tigecycline renal clearance in subjects with normal renal function represented approximately 20% of total systemic clearance. Tigecycline clearance was reduced by approximately 20%, and area under the tigecycline concentration-time curve increased by approximately 30% in subjects with severe renal impairment. Tigecycline was not efficiently removed by dialysis; thus, it can be administered without regard to timing of hemodialysis. Based on these pharmacokinetic data, tigecycline requires no dosage adjustment in patients with renal impairment.     

Pharmacokinetics of pregabalin in subjects with various degrees of renal function

The objectives of this study were to determine the single-dose pharmacokinetics of pregabalin in subjects with various degrees of renal function, determine the relationship between pregabalin clearance and estimated creatinine clearance (CLcr), and measure the effect of hemodialysis on plasma levels of pregabalin. Results form the basis of recommended pregabalin dosing regimens in patients with decreased renal function. Thirty-eight subjects were enrolled to ensure a wide range of renal function (CLcr < 30 mL/min, n = 8; 30-50, n = 5; 50-80, n = 7; and > 80, n = 6). Also enrolled were 12 subjects with renal impairment requiring hemodialysis. Each subject received 50 mg of pregabalin as two 25-mg capsules in this open-label, parallel-group study. Pregabalin concentrations were measured using previously validated liquid chromatographic methods. Pregabalin pharmacokinetic parameters were evaluated by established noncompartmental methods. Pregabalin was rapidly absorbed in all subjects. Total and renal pregabalin clearance were proportional (56% and 58%, respectively) to CLcr. As a result, area under the plasma concentration-time profile (AUC) and terminal elimination half-life (t1/2) values increased with decreasing renal function. Pregabalin dosage adjustment should be considered for patients with CLcr < 60 mL/min. A 50% reduction in pregabalin daily dose is recommended for patients with CLcr between 30 and 60 mL/min compared to those with CLcr > 60 mL/min. Daily doses should be further reduced by approximately 50% for each additional 50% decrease in CLcr. Pregabalin was highly cleared by hemodialysis. Supplemental pregabalin doses may be required for patients on chronic hemodialysis treatment after each hemodialysis treatment to maintain steady-state plasma pregabalin concentrations within desired ranges.     

Evaluation of predictability for vancomycin dosage regimens by the Bayesian method with Japanese population pharmacokinetic parameters

The predictability of serum vancomycin (VCM) concentrations by means of the Bayesian method was evaluated to establish whether the method can be used to select safe and effective VCM treatment regimens for individual patients. Serum VCM concentrations at the trough and 2 h after the end of infusion (peak) were measured. Pharmacokinetic parameters were calculated for VCM dosage regimens based on a two-compartment model with the Bayesian method, using the Japanese population pharmacokinetic parameters estimated by Yasuhara et al. (1998). The predictive performance for serum VCM concentrations and the dosage regimens were analyzed using two points of serum VCM concentration in 41 patients whose serum creatinine and age were in the ranges of 0.4-4.6 mg/dl and 24-92 years, respectively. Although the predicted values for trough and peak VCM concentrations were slightly lower than measured VCM concentrations, the predictive performance was generally good. There were no differences among the groups classified by serum creatinine or age. An examination of predicted data that differed markedly from the measured serum VCM concentrations indicated that a larger difference in volume of distribution at the steady state (Vdss) calculated from serum VCM concentrations at the beginning and revision of dosage regimens resulted in a poorer correlation of predicted values and measured values. This finding indicates that therapeutic drug monitoring should be conducted frequently, and the dosage regimen revised accordingly, in the case of patients who may have a change of Vdss of VCM, for example, due to a complication such as heart failure or edema.     

Interference of digoxin-like immunoreactive substances with three digoxin immunoassays in patients with various degrees of renal function

The effect of renal function and digoxin use in adult patients on interference from digoxin-like immunoreactive substances (DLIS) with three digoxin immunoassays was studied. Hospital patients entered into the study were categorized into the following groups according to renal function: group I (serum creatinine less than 1.5 mg/dL), group II (serum creatinine 1.5-2.5 mg/dL), group III (serum creatinine greater than 2.5 mg/dL, not on hemodialysis), and group IV (serum creatinine greater than 2.5 mg/dL, on maintenance hemodialysis). Medical records were reviewed to determine whether or not patients were receiving digoxin. Excess sera for analysis of serum digoxin concentrations (SDCs) was collected from routine laboratory tests. Serum samples were assayed singly by fluorescence polarization immunoassay (FPIA, Digoxin I, Abbott), radioimmunoassay (RIA, Micromedic), and affinity-column-mediated immunoassay (ACMIA, aca, E.I. du Pont). Correlation of SDCs obtained by RIA and ACMIA with FPIA results was determined using linear-regression analysis. A total of 177 patients met the study criteria; 98 were receiving digoxin. In patients on digoxin, SDCs by RIA were significantly higher than those obtained by FPIA in group II and III patients. SDCs obtained by ACMIA correlated well with and were not significantly different from those obtained by FPIA in any of the patient groups. Maximum differences and mean absolute differences in SDCs obtained by RIA were greater than those for ACMIA when compared with FPIA values in all patient groups. Over 40% of patients with renal dysfunction not on digoxin had false-positive SDCs by RIA; the highest of these values was seen in groups II and III.(ABSTRACT TRUNCATED AT 250 WORDS)     

Disposition of recombinant human interleukin-10 in subjects with various degrees of renal function.

The pharmacokinetics of intravenously administered recombinant human interleukin-10 (rHuIL-10) were evaluated in 18 subjects with creatinine clearances (Clcr) between 2.7 and 116.7 mL/min/1.73 m2. Serum samples for rHuIL-10 were obtained over a 48-hour period after a single 25 micrograms/kg i.v. bolus infusion. AUC, total body clearance (Clp), and steady-state volume of distribution (Vdss) were derived by compartmental methods. Analysis of serum concentrations showed statistically significant group differences for log-transformed AUC and original scale Clp (p < 0.01). The AUC and effective half-life increased, while the mean Clp of rHuIL-10 decreased as renal function declined. A linear relationship between AUC and Clcr as well as Clp and Clcr demonstrates that the disposition of rHuIL-10 is altered in subjects with renal insufficiency. No serious adverse events were noted.     

Pharmacokinetics and pharmacodynamics of pegfilgrastim in subjects with various degrees of renal function

A phase I study was conducted to evaluate the effects of renal function on the pharmacokinetics and pharmacodynamics (absolute neutrophil count [ANC]) of pegfilgrastim in nonneutropenic subjects. Thirty subjects categorized into 5 renal function groups (normal, mildly impaired, moderately impaired, severely impaired, and end-stage renal disease) received 1 subcutaneous injection of pegfilgrastim at 6 mg. The ANC profiles after pegfilgrastim administration were similar across different renal function groups. No discernable correlation between pharmacokinetic parameter values and degree of renal impairment was observed; the mean values ranged from 147 to 201 ng/mL for C(max) and from 7469 to 8513 ng x h/mL for AUC. Results suggest that the kidney has no important role in the elimination of pegfilgrastim. Therefore, no dosage adjustment for renal impairment is indicated for pegfilgrastim.     

The pharmacokinetics of quinapril and its active metabolite, quinaprilat, in patients with various degrees of renal function.

Single- and multiple-dose pharmacokinetics of quinapril and its active metabolite, quinaprilat, were determined after oral administration of 20 mg quinapril HCl on day 1 and days 4 through 10 in 17 normotensive subjects with various degrees of renal function. Blood and urine samples were collected over 72- and 24-hour periods, respectively, after the first single dose and last multiple dose for measurement of quinapril and quinaprilat concentrations. The renal clearance of quinapril and quinaprilat decreased with increasing renal insufficiency but did not result in significant changes in quinapril pharmacokinetics in patients with renal impairment. In contrast, quinaprilat maximum plasma concentration, trough and peak steady-state plasma concentrations, area under the plasma concentration-time curve, and half-life increased significantly with increasing renal insufficiency. The disposition of quinapril and quinaprilat was unchanged from single to multiple doses. Small changes in the pharmacokinetic disposition of quinapril, together with a decreased rate of quinaprilat elimination, resulted in increased quinaprilat plasma concentrations following administration of both single and multiple quinapril doses to normotensive patients with renal impairment. Thus, quinapril dosage adjustment may be required in some patients with renal impairment.     

Application of vancomycin in patients with varying renal function,especially those with augmented renal clearance

Context: Augmented renal clearance (ARC) refers to enhanced renal elimination of circulating solute, and has attracted wide attention in recent years.

Objective: This study evaluates the effects of ARC on serum vancomycin concentration in patients administered vancomycin.

Materials and methods: This was a retrospective study in patients receiving vancomycin treatment at a dose of 1000?mg in every 12?h and undergoing serum monitoring admitted over a 2-year period (May 2013 to May 2015), in order to estimate the influence of ARC on serum vancomycin concentration. In this study, statistical comparisons were made on the results from patients grouped according to creatinine clearance (CL_cr).

Results: One hundred forty-eight patients were enrolled in our study. The results showed that ARC patients were significantly younger, with a significantly lower S_cr and higher GFR. The CL_cr and steady-state trough concentrations of serum vancomycin exhibited a logarithmic correlation (Rs?=??0.699, R^2?=^?0.488, p?<?0.01) in the patients included in our study. The trough vancomycin concentrations of 62.9% patients in high CL_cr group were under 10?μg/mL.

Discussion and conclusion: Since ARC was significantly associated with subtherapeutic serum vancomycin concentration, it was necessary to devise adjusted dosage regimens for these patients based on their CL_cr.     

Differences in antimicrobial drug exposure in patients with various degrees of renal function based on recommendations from dosing references

STUDY OBJECTIVE: To calculate and compare 24-hour area under the unbound drug concentration-time curves (AUC(0-24)) of antimicrobials with dosing recommendations from six commonly used dosing references. INTERVENTION: Unbound plasma concentration-time profiles of 13 antimicrobial agents (4 penicillins, 3 cephalosporins, 2 carbapenems, aztreonam, 3 fluoroquinolones) were simulated at steady state using a one-compartment open model for a 70-kg adult based on pharmacokinetic parameters obtained from peer-reviewed literature. Simulations were performed at five levels of creatinine clearance (Cl(cr)). MEASUREMENTS AND MAIN RESULTS: Differences in AUC(0-24) for each antimicrobial agent were noted among the six references at each level of Cl(cr) as well as within references across the range of Cl(cr). In addition, up to 16-fold and 3-fold ranges in AUC(0-24) values were observed for beta-lactams and fluoroquinolones, respectively, in one reference based on dosing recommendations at a single level of Cl(cr) (due to more than one dose and/or dosing interval). CONCLUSION: Clinicians should be aware of differences among common references when selecting dosages of antimicrobial agents, especially for patients with moderate-to-severe renal impairment.     

万古霉素对老年人肾功能的影响

目的：观察万古霉素对老年人肾功能的影响。方法：25例老年严重感染患者，每天予万古霉素0.5-2.0g，分1－2次iv gtt，平均疗程9d，治疗前后观察血清肌酐，血尿素氮，尿酸和内生肌酐清除率的变化。结果：24例患者在应用万古霉素前后血清肌酐，血尿素氮，尿酸，内生肌酐清除率的变化无显著性差异（P＞0．05），仅1例患者出现急性肾功能衰竭。结论：老年人应用万古霉素大多数是安全的，应根据内生肌酐清除率调整用药剂量，进行血药浓度监测，谨慎与袢利尿剂合用。     

Predictive performance study of two digoxin assays in subjects with various degrees of renal function

This prospective study was conducted to compare the predictive performance of fluorescence polarization immunoassay (FPIA, Abbott TDx Digoxin II) and radioimmunoassay (RIA, Kallestad Labs) with combined low-pressure liquid chromatography/RIA (LPLC/RIA) digoxin assay in measuring 15-17 serum digoxin concentrations (SDC) obtained after a single 10 microg/kg intravenous digoxin dose in patients with various degrees of renal function and at different SDC ranges. Eighteen men and women were stratified into 3 age- and gender-matched groups based upon renal function [N = 6 in each, group I (Cl(cr) < 10 mL/min), group II (Cl(cr) = 10-50 mL/min), and group III (Cl(cr) > 50 mL/min)]. Serum digoxin concentrations were measured at time zero; at 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, and 12 hours; and at 2, 3, 4, and 5-7 days after the digoxin dose, using the three different digoxin assays. TDx Digoxin II was unbiased [mean error -0.09 (95% CI -0.19, 0.01)] and RIA biased [mean error -0.29 (95% CI -0.36, -0.21)] to over-predict SDC by 14.2%. In group I patients, the analysis revealed a bias to over-predict SDC by 6.0% for TDx Digoxin II [mean error -0.16 (95% CI -0.29, -0.07)] and an unbiased performance by RIA. In groups II and III, both TDx Digoxin II and RIA showed biased performance, the mean magnitude of bias was low (< 20%). For intermediate SDC range (> 0.5 ng/mL and < or = 3.0 ng/mL), TDx Digoxin II was unbiased in predicting SDC, whereas RIA was biased to under-predict SDC [mean error 0.13 (95% CI 0.10, 0.16)] by 9.9%. The magnitude of bias observed in all cases was less than 20%. Both assays, TDx Digoxin II and RIA, imprecisely measured SDC for all samples combined, different groups and SDC ranges. In all time-paired samples, TDx Digoxin II (FPIA) performed better than the RIA. In conclusion, the magnitude of bias observed with either assay at different groups and SDC ranges was not likely to be clinically relevant. Therefore, either assay may be used to measure SDC in clinical practice.     

Single dose pharmacokinetics of perindopril and its metabolites in hypertensive patients with various degrees of renal insufficiency.

1 Perindopril is a prodrug which is hydrolysed in vivo to the active metabolite perindoprilat, an angiotensin-converting enzyme inhibitor. Perindoprilat glucuronide is also found in plasma. 2 The pharmacokinetics of perindopril and its metabolites were studied after administration of a single 4 mg dose to hypertensive patients with various degrees of renal failure. 3 The absorption and elimination of perindopril were not influenced by the degree of renal failure. 4 The mean area under the serum concentration-time curve of the active metabolite perindoprilat increased from 93 ng ml-1 h in subjects with normal renal function to 1106 ng ml-1 in patients with severe renal failure, whereas its half-life varied from 5.0 to 27.4 h. 5 In the same subjects, the mean area under the curve of perindoprilat glucuronide increased from 78 to 513 ng ml-1 h, while its half-life varied from 1.8 h to 7.7 h. 6 Perindopril, perindoprilat, and perindoprilat glucuronide were dialysable. 7 The extent and duration of serum angiotensin-converting enzyme inhibition was augmented in renal failure. The mean area under the inhibition time curve (extrapolated to infinity) increased from 2490%.h in subjects with normal renal function to 42241 %.h in patients with severe renal impairment. The half-life of inhibition varied from 12.1 h to 100.4 h. This effect of renal failure on the pharmacodynamics of perindoprilat was more pronounced than its influence on perindoprilat kinetics. 8 In view of the important influence of renal impairment on the elimination and action of the active substance perindoprilat, a dosage reduction of perindopril is proposed in in patients with renal failure.(ABSTRACT TRUNCATED AT 250 WORDS)     

肾功能正常患者万古霉素稳态谷浓度分布及影响因素分析

目的 考察肾功能正常患者万古霉素稳态谷浓度的分布情况,明确影响万古霉素稳态谷浓度的相关因素。方法 收集肾功能正常(肌酐清除率≥50mL/min)且接受万古霉素常规给药方案(1g q12h)治疗的感染患者血样,采用酶免疫扩大法测定万古霉素稳态谷浓度,应用有序多元Logistic回归分析万古霉素稳态谷浓度与患者基本资料及生化指标的相关性。结果 纳入331例符合入排标准的感染患者,统计分析发现,41%(136/331)的患者万古霉素稳态谷浓度低于10μg/mL,而稳态谷浓度高于20μg/mL占15%(48/331),仅44%(147/331)的稳态谷浓度达到指南推荐的目标范围(10~20μg/mL)。有序多元Logistic回归结果显示,患者的年龄(P<0.001)、体重(P<0.001)、肌酐清除率(P<0.001)、重症感染(P=0.022)以及高血压(P=0.022)是影响万古霉素稳态谷浓度的危险因素。结论 可以根据患者的年龄、体重、肌酐清除率、感染类型及血压情况来综合调整万古霉素的给药方案,以更好地实现个体化用药。     

万古霉素用药后血清NGAL水平与肾功能变化的相关性研究

目的： 探讨万古霉素暴露的脓毒症患者血清中性粒细胞明胶酶相关脂质运载蛋白（NGAL）水平与肾功能变化的相关性,评价其在预测万古霉素暴露患者早期肾损害中的作用。方法： 以重症监护病房收治患者中接受万古霉素治疗并进行NGAL检测的脓毒症患者为研究对象。根据患者用药前NGAL水平,将纳入患者分为试验组和对照组2组,其中试验组为NGAL（+）组（≥ 50 ng·L^-1）,对照组为NGAL（-）组。分别记录2组患者用药前NGAL指标以及患者万古霉素用药前后血清肌酐（SCr）变化情况,白细胞计数（WBC）、C-反应蛋白（CRP）及降钙素原（PCT）等数据。以SCr绝对值增加>26.5 μmol·L^-1或增加达到基线值的1.5倍作为急性肾损伤（AKI）的诊断标准,评估NGAL水平与血肌酐变化、WBC、CRP及PCT之间的关系,比较NGAL（+）组和NGAL（-）组用药前后肌酐的变化情况及AKI发生率的统计学差异,并分析肾功能变化的影响因素。结果： 本研究共纳入患者69例,其中试验组28例,对照组41例。万古霉素用药前、后对照组患者血肌酐水平分别为（79.6±22.4）μmol·L^-1和（92.8±60.9）μmol·L^-1,试验组患者用药前后的血肌酐水平分别为（89.9±22.8）μmol·L^-1和（102.3±47.1）μmol·L^-1。2组间及用药前后血肌酐值差异均无统计学意义（P>0.05）。血清NGAL与患者用药前后血肌酐变化水平无相关关系（P=0.168,R=0.176）。试验组与对照组AKI的发生率分别为32.14%和24.39%,试验组略高于对照组,但其差异无统计学意义（P>0.05）。试验组中NGAL水平与WBC、CRP及PCT水平之间均无明显的相关关系。结论： 在患者入住ICU接受万古霉素治疗期间,血清NGAL尚不能证实单独作为万古霉素肾毒性的标记物。