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Discrepancies in the response to drugs are partially due to polymorphisms in genes involved in drug metabolism and transport. The frequency, pattern and impact of these polymorphisms vary among populations. In the present study, the pharmacokinetics and pharmacogenetics of atorvastatin (ATV) in a Mexican population were investigated. The study cohort exhibited differing ATV metabolizing phenotypes, and in subsequent allelic discrimination assays, single nucleotide polymorphisms in the angiotensinogen, angiotensin II type 1 receptor (AGTR1) and bradykinin B2 receptor (BDKRB2) genes were genotyped and their effects on the pharmacokinetic parameters of ATV were assessed. Additionally, association studies were performed to test for a correlation between metabolizing phenotypes and genetic variants. It was observed that carriers of the genotypes A/C and C/T in AGTR1 and BDKRB2 had higher area under the plasma concentration-time curve values from time 0 to the time of the last measurement and from time 0 extrapolated to infinity, and lower values of clearance of the fraction dose absorbed compared with homozygous carriers (P<0.05). Only the C/C genotype of BDKRB2 was associated with the fast metabolizer phenotype. These data suggest that AGTR1 and BDKRB2 are involved in ATV pharmacokinetics; a novel finding that requires confirmation in further studies.

Background: The antioxidant and anti-inflammatory effects of arbutin protect against a number of diseases. Objectives: The present study evaluated the protective effect of arbutin against carbon tetrachloride (CCl4)-induced hepatotoxicity in rats. Methods: Sixty-three Wistar rats were divided into nine groups. Groups I and II were the normal control groups. Group III, the hepatotoxic group, was given CCl4. Groups IV, VI, and VIII received different dosages of arbutin along with CCl4. Groups V, VII, and IX were administered different dosages of arbutin. The albumin content, total protein, and bilirubin were assayed to determine their serum and antioxidant levels; lipid peroxidation was assessed in the serum and liver tissue. Histological studies were carried out to confirm the biochemical results. Results: Treatment with CCl4 for 28 d decreased the levels of total protein and albumin and increased the level of bilirubin and lipid peroxidation. Arbutin treatment raised the level of albumin and lowered the lipid peroxidation to normal levels. Necrosis and fibrosis were observed in the liver tissue of CCl4-injected rats, and the administration of arbutin had a protective effect on the liver tissue. Conclusions: The results of this study showed that arbutin may protect the liver against CCl4-induced oxidative damage in rats. This hepatoprotective effect might be correlated with the antioxidant and free radical scavenger effects of arbutin.