CYP2E1, CYP2A6 and CYP3A5 enzymes belong to phase I group of drug-metabolizing enzymes, which are involved in the metabolism of various compounds and xenobiotics. Presence of polymorphisms in the genes coding for these enzymes results in interindividual variations in drug metabolism, therapeutic response and susceptibility towards various diseases. The frequencies of these variants in genes differ considerably between ethnic groups. This study was carried out to estimate the allele and genotype frequencies of common variants in CYP2E1, CYP2A6 and CYP3A5 in South Indian population. Six hundred and fifty-two unrelated healthy volunteers of South Indian origin (Andhra Pradesh, Karnataka, Kerala and Tamil Nadu) were included in this study. Polymerase chain reaction-restriction fragment length polymorphism, allele-specific PCR, real-time PCR, SNaPshot and gene sequencing methods were used for the identification of gene polymorphisms. The frequencies of CYP2E1*1B, CYP2E1*5B and CYP2E1*6 alleles in South Indian population were 14.3, 1.3 and 22.4%, respectively. The frequencies of CYP2A6*2, CYP2A6*4A and CYP2A6*5 alleles were found to be 1, 8.9 and 0.7%, respectively. The distribution of CYP3A5*3 allele was 63.5%. There were no variant alleles of CYP3A5*2, CYP3A5*4 and CYP3A5*6 in South Indian population. The frequencies of CYP2E1, CYP2A6 and CYP3A5 in the South Indian population are distinct from Caucasians, Chinese, Japanese, African Americans and other compared populations. This is the first study conducted in the South Indian population with a larger sample size. The findings of our study provide the basic genetic information for further pharmacogenomic investigations in the population.

Sodium valproate induced hyperammonaemic delirium with normal liver function tests is a relatively uncommon adverse effect. It may be mistaken for psychosis or worsening of mania leading to wrong diagnosis and improper management. Plasma ammonia levels should be monitored in all patients developing altered mental status after receiving valproate therapy. This is a case series of hyperammonaemic delirium due to valproate reported to the Department of Pharmacology from Department of Psychiatry over a period of one year.

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Objectives:The tolerability and efficacy of lanthanum carbonate has not been studied in the Indian population. This study was, therefore, undertaken to compare the efficacy and tolerability of lanthanum carbonate with calcium acetate in patients with stage 4 chronic kidney disease.Design:A randomized open label two group cross-over study.Materials and Methods:Following Institutional Ethics Committee approval and valid consent, patients with stage 4 chronic kidney disease were randomized to receive either lanthanum carbonate 500mg thrice daily or calcium acetate 667 mg thrice daily for 4 weeks. After a 4-week washout period, the patients were crossed over for another 4 weeks. Serum phosphorous, serum calcium, serum alkaline phosphatase, and serum creatinine were estimated at fixed intervals.Results:Twenty-six patients were enrolled in the study. The mean serum phosphorous concentrations showed a declining trend with lanthanum carbonate (from pre-drug levels of 7.88 ± 1.52 mg/dL-7.14 ± 1.51 mg/dL) and calcium acetate (from pre-drug levels of 7.54 ± 1.39 mg/dL-6.51 ± 1.38 mg/dL). A statistically significant difference was seen when comparing the change in serum calcium produced by these drugs (P < 0.05). Serum calcium levels increased with calcium acetate (from pre-drug levels of 7.01 ± 1.07-7.46 ± 0.74 mg dL), while it decreased with lanthanum carbonate (from pre-drug levels 7.43 ± 0.77-7.14 ± 0.72 mg/dL). The incidence of adverse effects was greater with lanthanum carbonate.Conclusion:Lanthanum carbonate and calcium acetate are equally effective phosphate binders with trends obvious in the first 4 weeks of therapy. The decrease in serum calcium levels with lanthanum carbonate when compared to the increase in serum calcium levels due to calcium acetate is statistically significant. The drawback of lanthanum carbonate is its high cost and relatively higher incidence of adverse events during treatment.

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