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The effect of neutropenia on the clinical pharmacokinetics of vancomycin in adults.
Bury, Didi; Ter Heine, Rob; van de Garde, Ewoudt M W; Nijziel, Marten R; Grouls, Rene J; Deenen, Maarten J.
Afiliación
  • Bury D; Department of Clinical Pharmacy, Catharina Hospital Eindhoven, Michelangelolaan 2, 5623 EJ, Eindhoven, The Netherlands.
  • Ter Heine R; Department of Pharmacy, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands. r.terheine@radboudumc.nl.
  • van de Garde EMW; Department of Clinical Pharmacy, St. Antonius Hospital, Koekoekslaan 1, 3435 CM, Nieuwegein, The Netherlands.
  • Nijziel MR; Division of Pharmacoepidemiology and Clinical Pharmacology, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands.
  • Grouls RJ; Department of Haematology, Catharina Hospital Eindhoven, Michelangelolaan 2, 5623 EJ, Eindhoven, The Netherlands.
  • Deenen MJ; Department of Clinical Pharmacy, Catharina Hospital Eindhoven, Michelangelolaan 2, 5623 EJ, Eindhoven, The Netherlands.
Eur J Clin Pharmacol ; 75(7): 921-928, 2019 Jul.
Article en En | MEDLINE | ID: mdl-30877327
AIM: There is accumulating evidence that neutropenic patients require higher dosages of vancomycin. To prevent sub-therapeutic drug exposure, it is of utmost importance to obtain adequate exposure from the first dose onwards. We aimed to quantify the effect of neutropenia on the pharmacokinetics of vancomycin. METHODS: Data were extracted from a matched patient cohort of patients known with (1) hematological disease, (2) solid malignancy, and (3) patients not known with cancer. Pharmacokinetic analysis was performed using non-linear mixed effects modeling with neutropenia investigated as a binary covariate on clearance and volume of distribution of vancomycin. RESULTS: A total of 116 patients were included (39 hematologic patients, 39 solid tumor patients, and 38 patients not known with cancer). In total, 742 paired time-concentration observations were available for the pharmacokinetic analysis. Presence of neutropenia showed to significantly (p = 0.00157) increase the clearance of vancomycin by 27.7% (95% CI 10.2-46.2%), whereas it did not impact the volume of distribution (p = 0.704). CONCLUSIONS: This study shows that vancomycin clearance is increased in patients with neutropenia by 27.7%. Therefore, the vancomycin maintenance dose should be pragmatically increased by 25% in neutropenic patients at the start of treatment. Since the volume of distribution appeared unaffected, no adjustment in loading dose is required. These dose adjustments do not rule out the necessity of further dose individualization by means of therapeutic drug monitoring.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vancomicina / Antibacterianos / Neutropenia Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Eur J Clin Pharmacol Año: 2019 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Alemania
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vancomicina / Antibacterianos / Neutropenia Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Eur J Clin Pharmacol Año: 2019 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Alemania