| ObjectiveA sensitive and rapid HPLC method was developed to determination of rifampicin and trimethoprim in biological specimen. The pharmacokinetics of rifampicin and trimethoprim was evaluated in 12 healthy subjects received co-rifampicin-trimethoprim capsules and rifampicin capsules. The pharmacokinetics of rifampicin and trimethoprim were investigated in order to evaluate the interaction between the two drugs and the rationality of drug combintion.MethodsTo determination the concentration of rifampicin in plasma and urine:The analysis was conducted with a ZORBAX Eclipse Plus C18 (4.6×150 mm,5μm) column using p-nitrophenol as internal standard, acetonitrile-0.05 mol-L"1 ammonium dihydrogen phosphate-triethylamine (pH3.5,36:64:0.l,v/v/v) was served as mobile phase, the detecting wavelengh was at 254 nm,flow rate was 1 mL-min-1.To determination the concentration of trimethoprim in plasma and urine:The analysis was conducted with a ZORBAX Eclipse Plus C18 (4.6×150 mm,5μm) column, acetonitrile-0.05 mol·L-1 ammonium dihydrogen phosphate-triethylamine (pH3.5,14:86:0.l,v/v/v) was served as mobile phase, the detecting wavelengh was at 230 nm,flow rate was 1 mL-min-1.To be applied to the clinical pharmacokinetics study of rifampicin and trimethoprim:The study was designed in a crossover, random, two-treatment, two-period test.12 healthy volunteers participating in this study were given a single oral dose as follows:the single group with rifampicin capsules administered at a dose of 300 mg; the combination group with Co-rifampicin-trimethoprim capsules (which is composed of rifampicin 300 mg, trimethoprim 80 mg). The drug concentrations of each ingredient were measured by HPLC assay individually. The pharmacokinetic parameters of two ingredients were calculated by statistical software DAS2.1.1. ResultsThe main pharmacokinetics parameters of rifampicin were very similar in the two groups:Tmax:1.46±0.66 h and 1.29±0.58h;Cmax:7.20±1.55μg/mL and 8.19±2.10μg/mL;t1/2:3.42±0.83 h and 3.21±0.62 h;Vd/F:37.7±3.98 L and 35.6±6.50 L;CL/F:8.15±2.44 L/h and 8.02±2.33 L/h;MRT0-t:4.26±0.38 h and 4.01±0.34 h; AUC0-t:35.5±9.08μg·h/mL and 37.1±11.1μg-h/mL; AUC0-∞:40.1±12.4μg-h/mL and 40.9±13.7μg-h/mL. The cumulative urinary excretion rates of rifampicin were (11.3±3.86)% and (11.6±4.86)% in 24 h, respectively. Statistical analysis was performed using the SPSS software (Version 13.0 for Windows). There was no significant difference between the two groups except the cumulative urinary excretion rates and excrete the biggest velocity between genders.2. The main pharmacokinetics parameters of trimethoprim were:Tmax:1.54±0.69 h;Cmax:0.84±0.15μg/mL;t1/2:8.15±1.82 h;Vd/F:88.3±18.9 L;CL/F:7.74±1.92 L/h;MRT0-t:10.5±1.80 h; AUC0-t:10.6±2.64μg·h/mL; AUC0-∞:10.9±2.78μg±h/mL L. The cumulative urinary excretion rates of trimethoprim were (49.6±6.15)% in 24 h. Statistical analysis was performed using the SPSS software (Version 13.0 for Windows). There was no significant difference between genders.ConclusionThere was no significant difference in main pharmacokinetics parameters after the healthy subjects randomly received a single oral dose of rifampicin capsules and co-rifampicin-trimethoprim capsules. The results showed that no interaction was found when the two drugs were administered incombination. This study can offer a valuable reference for clinic therapy. |
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