Ofloxacin population pharmacokinetics in patients with tuberculosis.
METHODS
Two tuberculosis hospitals in the United States.


OBJECTIVE
To determine the population pharmacokinetic (PK) parameters of ofloxacin following multiple oral doses.


METHODS
A total of 73 patients with tuberculosis (TB) participated in the study. Subjects received multiple doses of ofloxacin as part of their treatment. They also received concurrent medications based on in vitro susceptibility data. Serum samples were collected over 10 h and assayed by a validated high performance liquid chromatography (HPLC) assay. Concentration-time data were analyzed using population methods.


RESULTS
Ofloxacin concentrations increased linearly with increasing oral doses. Delayed absorption was seen at least once in 29% of patients. Ofloxacin elimination decreased with declining renal function and increasing age. Higher daily doses were well tolerated, and appeared to maximize the peak concentration to minimal inhibitory concentration ratio (Cmax:MIC).


CONCLUSIONS
Ofloxacin PK parameters were comparable to those previously published for other patient populations. Higher daily doses may offer pharmacodynamic advantages for the treatment of TB.
Stambaugh
J J
JJ
Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado, USA.
Berning
S E
SE
Bulpitt
A E
AE
Hollender
E S
ES
Narita
M
M
Ashkin
D
D
Peloquin
C A
CA
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015242:Ofloxacin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011159:Population Surveillance; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy*
D000890:Anti-Infective Agents; D015242:Ofloxacin