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.

Risk factors between analgesic use and chronic nephropathy in Thailand.

Analgesic abuse is common in Thailand. Heavy use of analgesic may also increase risk of chronic nephropathy. However, the extent of this risk remains unclear. We carried out a case-control study in three referral hospitals. A total of 84 patients with newly diagnosed of chronic tubulointerstitial nephritis were enrolled as cases. Two control groups were randomly selected, 192 from hospitalized patients who had no renal disease and serum creatinine below 1.2 mg/dl and 166 from relatives of friends visiting the hospitals. Both cases and controls were interviewed by a standardized pre-coded questionnaire to obtain histories of analgesic use before diagnosis of renal disease. On multiple logistic regression analysis, patients whose estimated lifetime use of acetaminophen of 1,000 g or more had an increased risk of chronic nephropathy compared with non-users, the odds ratio (OR) was 5.9 (95% confidence interval (CI) 1.3-25.6, hospital controls) and OR = 5.8 (95% CI 1.04-31.9, visitor controls). Also, uses of aspirin showed a similar relationship. Patients who used aspirin 1,000 g or more per lifetime had higher risk of chronic nephropathy when compared to non-users, the odds ratio were 7.1 (95% CI 2.0-25.8, hospital controls) and 20.4 (95% CI 2.4-174.2) for visitor controls. These data indicate that analgesic abuse increased risk of chronic nephropathy in Thailand.

Acute cyanide poisoning: a case report with toxicokinetic study.

Cyanide poisoning is a life threatening condition. But specific antidotes exist and can be easily prepared from available substances in hospital. Administration of antidotes will produce methemoglobin, which itself causes hypoxia. Nitrite induced methemoglobin can be extremely dangerous and even lethal. Before administering the antidotes, the diagnosis should be confirmed. Nitrite should not be given if the poisoning is mild or diagnosis is uncertain, to avoid excessive methemoglobin, dosage of sodium nitrite must be adjusted according to hemoglobin level (Table 1). Usage of sodium nitrite and sodium thiosulfate in the recommended doses are safe and effective for cyanide poisoning.