Quantitative determination of deferiprone in human plasma by reverse phase high performance liquid chromatography and its application to pharmacokinetic study

Deferiprone [1, 2 dimethyl-3-hydroxypyrid-4-one] is considered to be the standard iron chelator. Pharmacokinetic studies of generic formulations are required in local condition before placed on the market. High performance liquid chromatographic [HPLC] method was used for quantification of deferiprone in human plasma using UV/VIS detector. Chromatographic separation was carried out on C[18] column, with a mobile phase of methanol-buffer [18:82, v/v], pH 3.5, and caffeine was used as an internal standard. The calibration curve was linear over the range 0.25-10 micro g/mL in human plasma [R[2] = 0.9994]. After oral administration of deferiprone [500 mg] to human, the plasma concentration-time curve of deferiprone was conformed to two-compartment open model. The deferiprone plasma concentration showed a rapid absorption and average area under the plasma concentration-time curve [AUC] of deferiprone was 17.0 +/- 1.23 h. micro g/mL. Average absorption and elimination half-life values of deferiprone of 24 volunteers were 0.62 +/- 0.12 and 2.65 +/- 0.43 hours. This study confirms the rapid absorption of deferiprone in humans. AUC was similar to that previously reported but C[max] was slightly lower than that stated in the literature

Therapeutic effects of ciprofloxacin on the pharmacokinetics of carbamazepine in healthy adult male volunteers

Carbamazepine is a [CYP1A2 and CYP3A4 enzyme inducer] medicine which is used by epileptic patients for a long time. During the course of therapy, patients are generally caught by other diseases like urinary tract infections, upper respiratory tract infection, skin and soft tissue infection etc. To cure them, physicians commonly prescribe fluoroquinolones like Ciprofloxacin [CYP1A2 inhibitor] along with Carbamazepine [CBZ]. Interactions may result without recognition which may lead to unforeseen toxicity, untoward effects or even therapeutic failure. Therefore, studies were conducted to investigate the effect of Ciprofloxacin on the pharmacokinetics of Carbamazepine in healthy adult male volunteers. The main objective of this study was to generate new knowledge regarding CBZ and Ciprofloxacin interaction for physicians and research workers dealing with these medicines. Eight healthy adult male volunteers were selected to assess the effect of ciprofloxacin on the pharmacokinetics of Carbamazepine. After overnight fast the selected male volunteers were given CBZ orally. Blood samples were drawn at different time intervals after medication. Then the same volunteers were given CBZ along with ciprofloxacin. Blood samples were again drawn at the same time intervals as done previously. Plasma was separated from the blood samples. Concentration of CBZ in the plasma samples was determined by using HPLC technique. Results of the present study indicated that ciprofloxacin significantly increased the plasma concentration of CBZ when given concurrently to the healthy adult male volunteers. Ciprofloxacin increased C[max], AUC and t [1/2] while it decreased the CL and Vd of CBZ when administered concurrently to the adult volunteers. Change in pharmacokinetic parameters was due to slow metabolism or elimination of CBZ when given concurrently with ciprofloxacin to the adult volunteers. This is probably due to the inhibition of CYP3A4 isoenzyme by ciprofloxacin which is responsible for metabolism of CBZ. Ciprofloxacin increased the plasma concentration of CBZ so dose adjustment as well as drug monitoring of CBZ is required when both the drugs are given concurrently. The knowledge regarding interaction between ciprofloxacin and CBZ would be helpful for the pharmaceutical industries, physicians and a blessing for the patients