Pharmacokinetic parameters of vancomycin for therapeutic regimens in neutropenic adult patients

Vancomycin (V) is widely used in neutropenic patients, though its kinetics are known in this type of patient. In the present study, ten patients were included: all of them received an intensive therapy for non-Hodgkin malignant lymphoma, Hodgkin disease, myeloma, acute leukemia, followed by an autologous bone marrow transplantation in 6 cases. All patients were neutropenic (100/mm3). The pharmacokinetic study was done at the first V administration: 1000 mg V were injected as a 1-h infusion. Plasma V concentrations were measured by an enzyme immunoassay (EMIT, Syva, France). V maximal and minimal concentrations were 61.3 +/- 38.6 micrograms/ml and 1.69 +/- 0.77 microgram/ml, respectively. Total V clearance was 158 +/- 51 ml/min, with a creatinine clearance of 141.2 +/- 36.2 ml/min on test day. V plasma kinetics can be described by a biexponential model, with the following parameters: [table: see text] These data show a 3-fold increase of initial volume of distribution and a shortened (3-fold) T1/2 beta, if compared to values obtained in normal subjects. Because the bactericidal effect is time dependent, there can be a risk of insufficient antibiotic effect throughout the day. Our data suggest that new therapeutic regimens are needed for these patients.