Ceftriaxone is a cephalosporin antibiotic with a potent antimicrobial activity and excellent penetration in most body fluids such as pleural, peritoneal, spinal and brain. These facts contribute to the application of ceftriaxone in the treatment of bacterial peritonitis, an abdominal disorder in veterinary medicine, with potential risk of death. The determination of ceftriaxone levels in plasma and peritoneal fluid may be used to assess the pharmacokinetic profile at various instances of administration and allows observing if the concentrations needed are being achieved. Therefore a method was developed and validated for the determination of ceftriaxone in plasma and peritoneal fluid which after was applied in a pharmacokinetic profile study. The bioanalytical method validation was performed according to widely acceptable experiments. Two horses were used as a model of the method applicability; ceftriaxone was intraperitoneally administered to these animals as a single dose. The plasma and peritoneal fluid analysis were performed using an UHPLC system in reverse phase chromatography mode in fully validated conditions. The methods have shown linearity between 0.49 and 500μg/mL for plasma, and between 0.24 and 500μg/mL for peritoneal fluid. The quantitative analysis of ceftriaxone in these matrices allows monitoring of the therapy. This method showed improved sensitivity as well as the quantitation in peritoneal fluid.
A simple and rapid ultra-high-performance liquid chromatography (UHPLC) method for determination of efavirenz (EFV) in plasma was developed and applied in a preclinical pharmacokinetic study. The method involves only addition of acetonitrile to precipitation of plasma proteins followed by solvent evaporation. The mobile phase consisted of methanol, acetonitrile and 0.1 M formic acid (20:50:30) at a flow rate of 0.3 mL/min with run time of 5 min. A CSH C18 column and a UHPLC-UV system operating at 245 nm were used. There was a linear response in the range of 0.078 to 10 μg/mL, and the equation was obtained by weighting (1/x2) with r2 = 0.9965. The pharmacokinetic disposition of EFV was investigated in rabbits (two groups, n = 7) following a single intravenous administration (IV group) at a dose of 2.7 mg/kg and a single oral administration (oral group) of EFV co-administered with lamivudine (3TC) and tenofovir (TNF) at a dose of 50, 25 and 25 mg, respectively. The study demonstrated the applicability of the method for determination of EFV in plasma without interference from other co-administered drugs, and the pharmacokinetic parameters were calculated. The method showed advantages over other methods in the literature, such as simplicity of sample processing and fast results.
Tuberculosis treatment consists of a drug combination, where isoniazid is the core drug and alcoholism is a factor highly related to poor patient compliance with the therapy. CYP2E1 is an enzyme involved both in the metabolism of ethanol and in the formation of hepatotoxic compounds during the metabolism of isoniazid. The shared metabolism pathway accounts for the possibility of pharmacokinetic interaction in cases of concomitant alcohol use during tuberculosis treatment. The aim of this study was to evaluate the effect of repeated exposure of Wistar rats (males, 250 g, n=6) to ethanol on the pharmacokinetics of a single dose of isoniazid in combination with pyrazinamide and rifampicin (100 mg/kg, 350 mg/kg and 100 mg/kg, respectively). An animal group received the combination of drugs and ethanol and was compared to a control group, which received the combination of drugs without exposure to ethanol. The plasma concentrations of isoniazid were determined by a UHPLC/UV bioanalytical method that was previously validated. Biochemical markers of liver function were measured to assess potential damage. A lower elimination half-life of isoniazid was observed in the ethanol group than in the control group (t1/2 0.91 h versus 1.34 h). There was no evidence of hepatotoxicity through the biomarker enzymes evaluated. The results allow us to infer that although there are no biochemical changes related to liver damage, there is a slight influence of ethanol exposure on the pharmacokinetic profile of isoniazid. This change may have a relevant impact on the efficacy of isoniazid in the outcome of tuberculosis treatment.
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