Low Serum Concentrations of Moxifloxacin, Prothionamide, and Cycloserine on Sputum Conversion in Multi-Drug Resistant TB

PURPOSE: Low serum concentrations of drugs used to treat multi-drug resistant tuberculosis (MDR-TB) have occasionally been associated with treatment failure. We determined the frequencies of low serum concentrations of anti-MDR-TB drugs, and assessed the effects of these concentrations on 2-month sputum conversion. MATERIALS AND METHODS: The serum levels of moxifloxacin (MF), prothionamide (PTH), and cycloserine (CS) were determined for 89 serum samples by high-pressure liquid chromatography-tandem mass spectrometry. RESULTS: Low serum concentrations of MF, PTH, and CS below the minimal levels of the normal ranges were 83.3% (20/24), 59.2% (29/49), and 71.2% (47/66), respectively. There were no significant differences between the 2-month sputum conversion group (n=25) and the 2-month sputum non-conversion group (n=4) in median drug concentrations (microg/mL) of MF (1.46 vs. 1.60), PTH (0.91 vs. 0.70), and CS (14.90 vs. 14.90). However, a poor compliance rate was significantly greater in the 2-month sputum non-conversion group (75.0%, 3/4) than in the 2-month sputum conversion group (0%, 0/25) (p=0.001). CONCLUSION: The frequency of low serum concentrations of anti-MDR-TB drugs was substantial and might not affect the 2-month sputum conversion rate. Larger prospective studies with timely sampling are needed to investigate the role of therapeutic drug monitoring in MDR-TB.

Pharmacoknetic Study of Diclofenac and Its Interaction with Enrofloxacin in Buffalo Calves

A comparative pharmacokinetic study of diclofenac (1 mg/kg, i.v.) when given alone or in combination with enrofloxacin (4 mg/kg, i.v.) in five buffalo calves was carried out by using HPLC. The study revealed that the plasma concentrations of diclofenac were significantly lower (p<0.05) in combined administration of diclofenac with enrofloxacin (0.042 to 3 h), whereas significantly higher (p<0.05) levels of plasma drug concentrations were observed in later period (8 to 24 h). In urine, significantly lower (p<0.05) drug concentrations of diclofenac were observed from 0.167 to 1.5 h, whereas significantly higher (p<0.01) urine drug concentrations were observed in later period (4 to 48 h) when diclofenac was given in combination with enrofloxacin as compared to when diclofenac was given alone. Various kinetic parameters like A, Cpo and beta were significantly lower (p<0.05) whereas t1/2 beta, AUMC, MRT and various volume of distribution (VdC, VdB, Vdarea and VdSS) were significantly higher in combined administration of diclofenac with enrofloxacin as compared to when diclofenac was given alone (p<0.05).