Pharmacokinetics of levofloxacin in healthy Thai male volunteers.

The pharmacokinetics of levofloxacin, a new fluoroquinolone, were investigated in 12 healthy Thai male volunteers with an average age (SD) of 22.92 (2.50) years. A single oral dose of 300 mg or 500 mg levofloxacin was given to subjects following an 8- hour overnight fast. The drug was given in a controlled, randomized, 2 x 2 crossover design with a 1 week washout period. Venous blood samples were drawn prior to and from 0.25 up to 48 hours after dosing. Plasma levofloxacin concentrations were determined by HPLC assay. The pharmacokinetics of levofloxacin were well described by a linear, 2-compartment open model with first-order absorption with lag time and first-order elimination. Mean +/- SEM of Cmax after 300 mg and 500 mg dose was 4.83 +/- 0.33 and 7.75 +/- 0.71 micrograms/mL, respectively. Tmax ranged from 0.7 to 0.8 hours for both doses. Mean +/- SEM of AUC0-infinity was 35.77 +/- 2.06 micrograms x h/mL for 300 mg dose and 61.57 +/- 2.84 micrograms x h/mL for 500 mg dose. High distribution with VSS/F value of approximately 1.5 L/kg was demonstrated after both doses. Mean +/- SEM of CL/F value was 8.64 +/- 0.41 L/h and 8.31 +/- 0.37 L/h for a 300-mg and a 500-mg dose, respectively. Long t1/2 beta of 7 to 8 hours with the mean residence time of 10.43 +/- 0.43 hours and 10.49 +/- 0.38 hours after 300 mg and 500 mg dose, respectively, was observed. The results suggested that an oral 300 mg dose once daily provides sufficient Cmax to cover most Gram-negative and atypical bacteria (median MIC90 0.032-0.5 microgram/mL) common in mild to moderate respiratory tract infections or complicated urinary tract infections and Gram-positive bacteria (median MIC90 0.5 microgram/mL) common in skin and soft tissue infections. For severe cases or Streptococcus pneumoniae (MIC90 2 micrograms/mL) infection, a 500-mg dose should be recommended.

Lead exposure and accumulation in healthy Thais: assessed by lead levels, EDTA mobilization and heme synthesis-related parameters.

Lead is one of the pollutants which is of public concern. The magnitude of lead contamination in Thai people is of interest. The objective of this study was to evaluate the lead status in normal healthy volunteers. Normal volunteers were included. The blood for lead level, Zinc protoporphyrin (ZPP), delta-aminolevulinic acid dehydratase (ALA-D) activity, and baseline urine for lead, delta-aminolevulinic acid (ALA) and coproporphyrinogen III (CP3) were collected. The EDTA mobilization test was done. 24 hour urine after administration of the drug was collected for lead analysis. Thirty volunteers were included in the study. All were men whose average age was 32.5 +/- 6.9 years. The mean lead level was 5.95 +/- 2.01 micrograms/dL and 5.83 +/- 2.32 micrograms/L in urine. The 24 hour urine lead contents before and after EDTA administration were significantly different (11.11 +/- 6.72 and 16.05 +/- 9.51 micrograms respectively). Blood ALA-D activity was 251.6 +/- 80.4 unit/ml of RBC. Urine ALA and CP3 were 0.56 +/- 1.2 mg/L and 22.17 +/- 23.9 micrograms/L respectively. All were in the normal ranges. All parameters suggested that the healthy Thai volunteers had an acceptable magnitude of lead exposure and accumulation.