Do Vancomycin Pharmacokinetics Differ Between Obese and Non-obese Patients? Comparison of a General-Purpose and Four Obesity-Specific Pharmacokinetic Models

Abstract

Background: Over the past decade, numerous obesity-specific pharmacokinetic (PK) models and dosage regimens have been developed. However, it is unclear whether vancomycin PKs differ between obese and other patients after accounting for weight, age, and kidney function. In this study, the authors investigated whether using obesity-specific population PK models for vancomycin offers any advantage in accuracy and precision over using a recently developed general-purpose model. Methods: Vancomycin plasma concentrations in a cohort of 49 obese patients (body mass index [BMI] >30 kg/m2), not previously used in the development of any of the evaluated models, were used to validate the performance of 4 obesity-specific models and a general model. Bias and imprecision were calculated for the a priori and a posteriori predictive performance. Results: The bias of the a priori prediction was lowest for one of the obesity-specific models (−1.40%) and that of the general model was a close second (−7.0%). The imprecision was lowest for the general model (4.34 mg/L). The predictive performance for the a posteriori predictions was best for the general model, both for bias (1.96%) and imprecision (2.75 mg/L). Conclusions: The results of the external validation of vancomycin PK in obese patients showed that currently available obesity-specific models do not necessarily outperform a broadly supported general-purpose model. Based on these results, the authors conclude that there is no advantage in using vancomycin PK models specifically tailored to obese patients over the general-purpose model reported by Colin et al.

Clinical Practice Guidelines for Therapeutic Drug Monitoring of Vancomycin in the Framework of Model-Informed Precision Dosing: A Consensus Review by the Japanese Society of Chemotherapy and the Japanese Society of Therapeutic Drug Monitoring

“… Better prior probability was reported in a population PK model based on rich sampling (full data set: e.g., at the end of infusion, at 60, 120, and 300 min following the infusion, and immediately before the next dose) than that based on limited sampling (e.g., trough and peak concentrations) [ 66 , 67 , 68 , 69 , 70 , 71 ]. Population properties (i.e., age, body weight, kidney function, other potential covariates) for establishing a population PK model should be considered to determine the reasonable candidates for the MIPD software to increase the accuracy of dosing [ 53 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 ]. The Bayesian prior information has been accumulated in special populations of obesity, paediatrics, and renal replacement therapy (RRT).…”

“…Population properties (i.e., age, body weight, kidney function, other potential covariates) for establishing a population PK model should be considered to determine the reasonable candidates for the MIPD software to increase the accuracy of dosing [ 53 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 ].…”

“…The ratio of the Bayesian posterior AUC using trough sampling to AUC F-F ranged 0.87 (95% CI = 0.77–0.97) to 1.30 (95% CI = 1.19–1.40) among the three population PK models developed in nonspecific to obese patients. Colin et al reported root mean square errors (as the index for predictive performance, smaller is better) for concentrations measured using two general population PK models of 2.44 and 4.18 μg/mL, respectively, whereas that measured using four obese population PK models ranged from 3.06 to 3.64 μg/mL among morbidly obese patients [ 73 ]. Taken together, although some population PK models have been reported for obese patients [ 61 , 63 , 71 ], a general population PK model may be used for Bayesian posterior AUC estimation in obese patients.…”

Clinical validation of pharmacokinetic/pharmacodynamic models for propofol infusion. Response to Br J Anaesth 2021: 126: e172-4

“…Specialised models are not always an improvement in TCI performance. Colin and collegues 5 showed that for vancomycin there is no advantage in using vancomycin pharmacokinetic models specifically tailored to obese patients over the general purpose model. For propofol, we suggest that broad application of our model is a better choice, not only for 'edge-cases' but also for specialised populations for which models are available 6 since there is currently no evidence that specialised models obtain a clinically meaningful improvement in TCI system performance.…”

“…To minimise perioperative DKA risk, current guidelines recommend withholding SGLT2i for 48 h before surgery (where fasting and anaesthesia are required) 3,4 ; otherwise, postponement should be considered. 5 Further research is required to understand the optimal management approach, where SGLT2i has been administered within 48 h before surgery. We report metabolic outcomes in a case series of patients treated with SGLT2i immediately before emergency or elective surgery.…”