Population pharmacokinetics of vancomycin in obesity: Finding the optimal dose for (morbidly) obese individuals.
Br J Clin Pharmacol
; 86(2): 303-317, 2020 02.
Article
en En
| MEDLINE
| ID: mdl-31661553
ABSTRACT
AIMS:
For vancomycin treatment in obese patients, there is no consensus on the optimal dose that will lead to the pharmacodynamic target (area under the curve 400-700 mg h L-1 ). This prospective study quantifies vancomycin pharmacokinetics in morbidly obese and nonobese individuals, in order to guide vancomycin dosing in the obese.METHODS:
Morbidly obese individuals (n = 20) undergoing bariatric surgery and nonobese healthy volunteers (n = 8; total body weight [TBW] 60.0-234.6 kg) received a single vancomycin dose (obese 12.5 mg kg-1 , maximum 2500 mg; nonobese 1000 mg) with plasma concentrations measured over 48 h (11-13 samples per individual). Modelling, internal validation, external validation using previously published data and simulations (n = 10.000 individuals, TBW 60-230 kg) were performed using NONMEM.RESULTS:
In a 3-compartment model, peripheral volume of distribution and clearance increased with TBW (both p < 0.001), which was confirmed in the external validation. A dose of 35 mg kg-1 day-1 (maximum 5500 mg/day) resulted in a > 90% target attainment (area under the curve > 400 mg h L-1 ) in individuals up to 200 kg, with corresponding trough concentrations of 5.7-14.6 mg L-1 (twice daily dosing). For continuous infusion, a loading dose of 1500 mg is required for steady state on day 1.CONCLUSION:
In this prospective, rich sampling pharmacokinetic study, vancomycin clearance was well predicted using TBW. We recommend that in obese individuals without renal impairment, vancomycin should be dosed as 35 mg kg-1 day-1 (maximized at 5500 mg/day). When given over 2 daily doses, trough concentrations of 5.7-14.6 mg L-1 correspond to the target exposure in obese individuals.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Obesidad Mórbida
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Vancomicina
Tipo de estudio:
Diagnostic_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Br J Clin Pharmacol
Año:
2020
Tipo del documento:
Article
País de afiliación:
Países Bajos