Evaluation of Bayesian Predictability of Vancomycin Concentration Using Population Pharmacokinetic Parameters in Pediatric Patients

Ohnishi, Ayako; Yano, Yoshitaka; Ishibashi, Tôru; Katsube, Takayuki; Oguma, Takayoshi

doi:10.2133/dmpk.20.415

Cited by 9 publications

(10 citation statements)

References 28 publications

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“…The observed relationship between serum clearance of vancomycin and postmenstrual age agree with the fact that vancomycin is cleared renally by glomerular filtration and that there is a positive relationship between postmenstrual age and maturation of renal function [17–19].…”

Section: Discussionsupporting

confidence: 82%

Population pharmacokinetic analysis of vancomycin in neonates. A new proposal of initial dosage guideline

Marqués-Miñana¹,

Saadeddin

Peris

2010

Brit J Clinical Pharma

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Vancomycin is a glycopeptide antibiotic commonly used to treat resistant gram-positive infections in neonates. While adult dosing guidelines are generally well established, a lack of consensus for optimal dosing regimens in neonates remains.• The large variance in pharmacokinetic values in premature neonates compared with full-term infants is a major barrier to the development of optimal dosing regimens. Pharmacokinetic values have been reported for vancomycin in neonates. However, the studies have included small groups with differing, clinical conditions, serum sampling times and pharmacokinetic models. There are many proposed neonatal dosing guidelines for vancomycin, but few, if any, have been prospectively evaluated. In addition, the complexity of the dose and interval selection has led to errors in use. WHAT THIS STUDY ADDS• The purpose of this investigation was to determine population pharmacokinetic parameters of vancomycin in neonatal patients with a wide range of gestational age and birth weight and to study the effect of the co-administration of amoxicillin-clavulanic acid and spironolactone on the pharmacokinetics of vancomycin in this cohort of patients. The aim was to find covariates with a relevant influence on the pharmacokinetic parameters of this drug, and to use this information for the design of an initial dosing schedule of vancomycin in neonates. Additionally, the obtained population pharmacokinetic parameters can be used to perform modifications of the initial dosing schedule in neonates with serum concentrations outside of the therapeutic range, by means of a Bayesian approach. AIMTo determine the population pharmacokinetic parameters of vancomycin in neonatal patients with a wide range of gestational age and birth weight, and subsequently to design an initial dosing schedule for vancomycin in neonates. METHODSUsing nonlinear mixed-effects modelling (NONMEM VI), the pharmacokinetics of vancomycin were investigated in 70 neonates with postmenstrual age and body weight ranging 25.1-48.1 weeks and 0.7-3.7 kg, respectively. A one-compartment linear disposition model with zero order input and first-order elimination was used to describe the data. Nine demographic characteristics and 21 co-administered drugs were evaluated as covariates of clearance (CL) and distribution volume (V d) of vancomycin. RESULTSWeight-normalized clearance of vancomycin was influenced by postmenstrual age (PMA) and co-administration of amoxicillin-clavulanic acid. Weight-normalized volume of distribution was influenced by co-administration of spironolactone. CL and Vd of the typical individual in this study population (PMA = 34.6 weeks, weight = 1.7 kg) were estimated to be 0.066 l h -1 kg -1 (95% CI 0.059, 0.073 l h -1 kg -1) and 0.572 l kg -1 (95% CI 0.505, 0.639 l kg), respectively. This model was used to predict a priori serum vancomycin concentrations in a validation group (n = 41), which were compared with observed concentrations to determine the predictive performance of...

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Section: Discussionsupporting

confidence: 82%

Population pharmacokinetic analysis of vancomycin in neonates. A new proposal of initial dosage guideline

Marqués-Miñana¹,

Saadeddin

Peris

2010

Brit J Clinical Pharma

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“…Because kinetic disposition is quite different between adult patients and pediatric patients due to differences in body size, fluid compartments and drug elimination by urinary excretion or drug metabolism (Onishi et al, 2005), these data may agree with the previous studies.…”

Section: Therapeutic Drug Monitoringsupporting

confidence: 89%

Pharmacokinetic-pharmacodynamic correlation of imipenem in pediatric burn patients using a bioanalytical liquid chromatographic method

Santos

Sanches

Júnior

et al. 2015

Braz. J. Pharm. Sci.

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A bioanalytical method was developed and applied to quantify the free imipenem concentrations for pharmacokinetics and PK/PD correlation studies of the dose adjustments required to maintain antimicrobial effectiveness in pediatric burn patients. A reverse-phase Supelcosil LC18 column (250 x 4.6 mm 5 micra), binary mobile phase consisting of 0.01 M, pH 7.0 phosphate buffer and acetonitrile (99:1, v/v), flow rate of 0.8 mL/min, was applied. The method showed good absolute recovery (above 90%), good linearity (0.25-100.0 µg/mL, r 2 =0.999), good sensitivity (LLOQ: 0.25 µg/mL; LLOD: 0.12 µg/mL) and acceptable stability. Inter/intraday precision values were 7.3/5.9%, and mean accuracy was 92.9%. A bioanalytical method was applied to quantify free drug concentrations in children with burns. Six pediatric burn patients (median 7.0 years old, 27.5 kg), normal renal function, and 33% total burn surface area were prospectively investigated; inhalation injuries were present in 4/6 (67%) of the patients. Plasma monitoring and PK assessments were performed using a serial blood sample collection for each set, totaling 10 sets. The PK/PD target attained (40%T>MIC) for each minimum inhibitory concentration (MIC: 0.5, 1.0, 2.0, 4.0 mg/L) occurred at a percentage higher than 80% of the sets investigated and 100% after dose adjustment. In conclusion, the purification of plasma samples using an ultrafiltration technique followed by quantification of imipenem plasma measurements using the LC method is quite simple, useful, and requires small volumes for blood sampling. In addition, a small amount of plasma (0.25 mL) is needed to guarantee drug effectiveness in pediatric burn patients. There is also a low risk of neurotoxicity, which is important because pharmacokinetics are unpredictable in these critical patients with severe hospital infection. Finally, the PK/PD target was attained for imipenem in the control of sepsis in pediatric patients with burns.Uniterms: Imipenem/quantification. Antibiotics/dosage. Pediatric patients/burn/antibiotics use. High Performance Liquid Chromatography/quantitative analysis. Drug plasma monitoring. PK/PD.Desenvolveu-se e aplicou-se método bioanalítico para quantificar concentrações de imipenem livre para estudos de farmacocinética (PK) e de correlação PK/PD dos ajustes de dose requeridos para manter a efetividade antimicrobiana em pacientes pediátricos queimados. Utilizou-se coluna Supelcosil LC18 (250 x 4,6 mm 5 micra), fase móvel binária, consistindo de tampão fosfato 0,01M pH 7,0 e acetonitrila (99:1, v/v) e fluxo de 0,8 mL/min. O método mostrou boa recuperação absoluta (acima de 90%), boa linearidade (0,25-100,0 µg/mL, r 2 =0.999), boa sensibilidade (LLOQ: 0,25 µg/mL; LLOD: 0,12 µg/mL) e estabilidade aceitável. Os valores de precisão inter/intradia foram 7,3/5,9% e a exatidão média foi de 92,9%. O método bioanalítico foi aplicado para quantificar concentrações de fármaco livre em crianças com queimaduras, Seis pacientes pediátricos queimados (idade média de 7,0 anos, 27,5 kg), com função renal n...

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“…According to these results, Bayesian predictability seems generally acceptable. The accuracy of Bayesian estimation depends on sampling times, [24][25][26] and it is reported that the estimation error for distribution volume is large but that for clearance is relatively small in case using only trough data.…”

Section: Comparison Of Patients' Characteristicsmentioning

confidence: 99%

A Retrospective Analysis of Vancomycin Pharmacokinetics in Japanese Cancer and Non-cancer Patients Based on Routine Trough Monitoring Data

Omote

Yano

Hashida

et al. 2009

Biological & Pharmaceutical Bulletin

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The pharmacokinetics of vancomycin was retrospectively examined based on trough concentrations obtained during routine therapeutic drug monitoring to examine possible pharmacokinetic differences between adult Japanese cancer and non-cancer patients with various degrees of renal function. A total of 231 data points from 65 cancer patients and 41 non-cancer patients were collected, and patients' background, vancomycin dose, and vancomycin clearance estimated by an empirical Bayesian method were summarized. Regarding the patients' characteristics and clinical laboratory test data, no clear differences were found between the two groups. The relationship between vancomycin clearance and creatinine clearance were similar between the groups, suggesting little effect of malignancy on vancomycin clearance. After the sub-group comparisons regarding fluid retention and cancer type, no clear differences were found in the vancomycin clearance versus creatinine clearance relationship. We conclude that the initial dose of vancomycin should not necessarily be adjusted for cancer patients. For individualized vancomycin-based therapy, dose adjustment at the appropriate time is important according to information from routine therapeutic drug monitoring and clinical laboratory tests, and to observations of the efficacy, nephrotoxicity, and other conditions in each patient.

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Evaluation of Bayesian Predictability of Vancomycin Concentration Using Population Pharmacokinetic Parameters in Pediatric Patients

Cited by 9 publications

References 28 publications

Population pharmacokinetic analysis of vancomycin in neonates. A new proposal of initial dosage guideline

Population pharmacokinetic analysis of vancomycin in neonates. A new proposal of initial dosage guideline

Pharmacokinetic-pharmacodynamic correlation of imipenem in pediatric burn patients using a bioanalytical liquid chromatographic method

A Retrospective Analysis of Vancomycin Pharmacokinetics in Japanese Cancer and Non-cancer Patients Based on Routine Trough Monitoring Data

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