Histopathological Effects of Carbamazepine on The Reproductive System of Male Rats

This research aims to identify the effect of carbamazepine on genital tissues of male rats. In this experiment (20) male from adult rats were randomly assigned to 2 groups, Each group comprises (10) animals. Control group gavage with distilled water, First group gavage carbamazepine concentration (30) mg/kg of body weight. After 45 days, genitals eradicated for the purpose of textile on study them, Histological examination showed pathological changes in the occurrence of the testis in (T1) represented by its small diameter tubular deferens Also, the number of cells formed for sperm cells and spermatid and leydig cells has been reduced and cells for Spermatogonia get necrosis of the facility.

Method Validation for the Determination of Carbamazepine in Spiked-saliva Using HPLC-UV for Therapeutic Drug Monitoring Application

Background:: Carbamazepine has been used in the treatment of bipolar disorder, both in acute mania and maintenance therapy, particularly in developing countries. Not only its interaction with various drugs and auto-inducer nature, but the narrow therapeutic range of carbamazepine also makes monitoring necessary to guarantee the adequacy of its safety and therapeutic concentration. To date, the most common biological specimen used for therapeutic drug monitoring (TDM) purposes is still plasma, but saliva can become an alternative biological matrix since its level in saliva strongly correlates with carbamazepine plasma concentration. Objective:: This study validated the bioanalytical method parameters used for carbamazepine in spiked-saliva in accordance with the Food and Drug Administration (FDA) criteria in the Guidance for Industry Bioanalytical Method Validation. Methods: HPLC-UV detector was employed at 285 nm λ with methanol: water: glacial acetic acid (65:34:1) as the mobile phase and C8 as the stationary phase (4.6x150 mm; 5 μm). Results:: The linearity test in a range of 0.0 - 5 μg/mL carbamazepine concentration resulted in a correlation coefficient of 0.999 with 0.20 μg/mL LoD, 0.30 μg/mL LLoQ, and 0.61 μg/mL LoQ. The coefficient of variation and 0iff in the selectivity, accuracy, and precision parameters remained below 20%, indicating fulfillment of the criteria for a bioanalytical method, while the average % recovery was more than 90%. Conclusion:: The currently-developed bioanalytical method has fulfilled the stipulated validation criteria to be used for determining carbamazepine concentration in spiked-saliva as an alternative method for relative bioequivalence studies or TDM application in a clinical setting.

Limited Efficacy of Gastrointestinal Decontamination in Severe Slow-Release Carbamazepine Overdose

Objective: To report the limited efficacy of both multiple doses of activated charcoal (MDAC) and whole bowel irrigation (WBI) in a patient with severe overdose of slow-release carbamazepine. Case Summary: A 25-year-old man was admitted in a comatose state with seizures after a suicide attempt with slow-release carbamazepine. Serum carbamazepine concentration on admission (16 h postingestion) was 52.08 μg/mL. The patient was mechanically ventilated and treated with MDAC and a 4 hour charcoal hemoperfusion. Carbamazepine concentration at the end of hemoperfusion was 27.16 μg/mL. Despite continuous treatment with MDAC, a rebound in carbamazepine concentration to 36 μg/mL was observed 32 hours after hemoperfusion (58 h postingestion). WBI was performed over a 10 hour period. The carbamazepine concentration continued to increase to 38.55 μg/mL and seizures recurred. After WBI was performed, MDAC was reinstituted; 33 hours later (102 h postingestion), the carbamazepine concentration began to decline. The hospitalization course was complicated by pneumonia, which necessitated continuation of mechanical ventilation and administration of antibiotics. The patient recovered completely and was discharged without sequelae 15 days after admission. Discussion: Serum carbamazepine concentration and toxicity were effectively reduced by hemoperfusion. The role of MDAC coadministered during hemoperfusion cannot be ruled out. However, a rebound in carbamazepine concentration with recurrent seizures was observed despite MDAC and WBI. The most likely explanation for this rebound (65 h postingestion, 39 h posthemoperfusion) is prolonged absorption, possibly from a pharmacobezoar. Redistribution cannot be excluded, but this is not supported by the concentration–time course and previous reports. Conclusions: Both MDAC and WBI may be ineffective in reducing absorption and enhancing elimination in overdose of slow-release carbamazepine. Repeated hemoperfusion or other elimination enhancement techniques should be considered when the clinical and toxicokinetic course suggests the presence of a refractory pharmacobezoar.