Population pharmacokinetics of levofloxacin as prophylaxis for febrile neutropenia.
BACKGROUND
Levofloxacin (LVFX) is widely used against a broad spectrum of bacteria. To prevent the emerging of resistance resulting from its abuse, an optimal method and dosage are needed. In the field of hematological malignancies, LVFX is one of the choices for prophylaxis for febrile neutropenia (FN). There is no consensus about the optimal dosage and method among hematologists. Aims To determine the population pharmacological parameters based on the population pharmacokinetics of LVFX. We considered the optimal dosage and method of LVFX based on various simulations depicted by personal computer.


METHODS
We performed population pharmacokinetic analysis for seven patients receiving LVFX as prophylaxis (200 mg, b.i.d.) for FN with blood sampling. One patient received 100 mg t.i.d. All patients were treated at Kyoto Prefectural University of Medicine.


RESULTS
Clearance (CL) is 5.8 L/hr, distribution volume (Vd) is 58.5 L, area under the blood concentration-time curve (AUC(0-24)) is 69.0 microg x hr/mL, t1/2 is 6.9 hr, Cmax is 3.4 microg/mL at administration of 200 mg b.i.d. Cmax (peak) of 500 mg, and q.d. is simulated as 8.54 microg/mL.


CONCLUSIONS
For LVFX 500 mg q.d. is predicted to be the most effective dosage and method. Because the predicted Cmax value is similar to that of western countries, the frequency of adverse effects is thought to be same as in western countries. 500 mg, q.d., may also be an optimal dosage and method for Japanese.
Nomura
Kenichi
K
Department of Hematology and Oncology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science. nomuken@koto.kpu-m.ac.jp
Fujimoto
Yoshiko
Y
Morimoto
Yasutaka
Y
Kanbayashi
Yuko
Y
Matsumoto
Yosuke
Y
Taniwaki
Masafumi
M
D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D019072:Antibiotic Prophylaxis / Q000379:methods; D004305:Dose-Response Relationship, Drug; D005260:Female; D005334:Fever; D006801:Humans; D007564:Japan; D007938:Leukemia / Q000150:complications; D064704:Levofloxacin; D008223:Lymphoma / Q000150:complications; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009503:Neutropenia / Q000150:complications / Q000188:drug therapy; D015242:Ofloxacin / Q000493:pharmacokinetics*; D010865:Pilot Projects
D000900:Anti-Bacterial Agents; D064704:Levofloxacin; D015242:Ofloxacin