This work was performed to explore the effect of polymorphism in multidrug resistant genes on plasma phenytoin levels and patient outcome to evaluate its involvement in drug resistance and toxicity, which is usually associated with antiepileptic drugs. Therefore, we genotyped the adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1) in 100 patients suffering from partial or generalized tonic-clonic seizures and receiving phenytoin and 50 healthy control subjects. Steady state plasma phenytoin levels were also determined in the epileptic patients. Patients were evaluated after 3 and 6 months and were classified either as drug resistant patients or responsive patients. Results revealed 37 patients with drug responsive epilepsy and 63 patients with drug resistant epilepsy. Genotyping of our patients and control subjects revealed a genotype distribution of CC, CT, TT: 55.50%, 38.00%, 6.50% for drug resistant patients, CC, CT, TT: 13.50%, 46.00%, 40.50% for drug responsive patients, and CC, CT, TT: 24.00%, 48.00%, 28.00% for the control subjects. Patients with drug-resistant epilepsy were more likely to have the CC than the TT genotype compared with either responsive patients (P < 0.0001) or control subjects (P < 0.0001). The C polymorphism was over-represented among patients with drug-resistant epilepsy as compared with either those with drug-responsive epilepsy (P < 0.001) or control subjects (P < 0.001). Of the total 100 epileptic patients, 13 patients had their plasma phenytoin levels exceeding the maximum safe concentration. These 13 patients were more likely to have TT genotype than the CC genotype compared with the remainder of patients who had their plasma phenytoin levels at 20 microg/mL or less. Responsive patients showed no deviation from the control group regarding the genotype (P > 0.05) or allele frequency (P > 0.05). In conclusion, because most of the antiepileptic drugs are multidrug resistant gene substrates, the ABCB1 is thus an important candidate gene for potentially influencing the response to antiepileptic drugs. Our findings suggest that using genotype data may make it possible to safely reduce the time required to reach an effective dose. Therefore, it is a priority to assess the utility of dose adjustment on the basis of genotype for these medicines that are substrates for this gene.

Background: The incidence of Type 2 Diabetes Mellitus (T2DM) in Egypt is considered one of the highest in the world. Metformin and Sulfonylureas are usually prescribed together due to their efficacy and their relatively low cost. Organic cation transport 1, encoded by SLC22A1 gene, is the main transporter of metformin into hepatocytes, which is considered metformin site of action. Sulfonylureas enhance insulin release from pancreatic B- cells through binding to sulfonylurea receptor 1, encoded by ABCC8 gene. Single nucleotide polymorphisms in the SLC22A1 and ABCC8 genes might affect the response of each drug. Aims: To investigate the influence of SLC22A1 rs622342 (A>C) and ABCC8 rs757110 (A>C) genetic variants on the efficacy of metformin and glimepiride combination therapy in Egyptian T2DM patients. Methods: Observational cross-sectional study in which patients receiving metformin and glimepiride combination therapy for at least 6 months were included for genotyping and classified into either responders or non-responders, based on their HbA1C level. Results: A total of 127 patients were included and genotyped. They were divided into 93 responders (HbA1C<7%) and 34 non-responders (HbA1C≥7%). Minor allele frequencies for rs622342 and rs757110 were 0.189 and 0.271, respectively. Only SLC22A1 rs622342 variant was found to be associated with the response of combination therapy, in which AA alleles carriers were 2.7-times more responsive to metformin than C allele carriers (Recessive model, odds ratio = 2.718, p = 0.025, 95% CI = 1.112–6.385). Conclusion: Genotyping of rs622342 can be useful in predicting the response to metformin in combination therapy in Egyptian T2DM patients.

This work was performed to study the pharmacokinetics of phenobarbital during renal clearance enhancement, intestinal clearance enhancement, and a combination of both to determine which method is clinically more effective in the management of drug poisoning. Thirty young patients with phenobarbital overdose were enrolled in the study. They were classified according to the method of treatment to enhance the elimination of phenobarbital into three equal groups: those treated with multiple-dose activated charcoal (MDAC) alone; those treated with urinary alkalinization alone; and those treated with a combination of the two methods. All patients received the required supportive care at the same time as the elimination procedures. Plasma phenobarbital levels were determined on admission and at 6, 12, 18, 24, 30, 36, 42, and 48 hours after admission by the enzyme multiplied immunoassay technique. The results showed that the decrease in plasma phenobarbital levels with MDAC was significantly greater than with either urinary alkalinization or the combined use of both. The results also revealed statistically significant greater total body clearance for phenobarbital and consequently a shorter half-life with MDAC treatment versus either urinary alkalinization alone or the combined use of both. Thus, the authors conclude that the management of drug overdose in the case of weak acidic drugs that have small volumes of distribution should include the sole use of MDAC and supportive care, without urinary alkalinization.

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