The myelotoxicity in patients receiving FAC is related to the activity of the phase-II enzyme GSTA1 but is independent of the formation of 4-OH-CP.

Polymorphic genes of drug metabolizing enzymes and transporters may influence drug response. With some exemptions, single nucleotide polymorphisms in such genes, however, are not known to be susceptibility factors for breast cancer. This study explored genotype profiles for the breast cancer patients on fluorouracil, doxorubicin and cyclophosphamide (FAC) in a Pakistani set of population and their comparison with HapMap data. Sixty-eight female breast cancer patients were included. All received FAC chemotherapy. Relevant genotyping was done either through restriction fragment length polymorphism or pyrosequencing. The variant allele frequencies were: 5.1% for CYP2C9*2 (430C>T), 15.4% for CYP2C9*3 (1075A>C), 27.2% for CYP2C19*2 (681G>A), 33.1% for GSTA1*B (-69C>T, -52G>A), 62.5% for ALDH3A1*2 (985C>G), 58.8% and 4.4% for ABCB1 (2677 G>T/A), 64.7% for ABCB1 3435 C>T, and 15.4%, 33.1% and 39.7% for ABCC2 (-24 C>T, 1249 G>A and 3972 C>T). In comparison with HapMap, this first exploration in Pakistani samples shows higher frequency of (i) CYP2C9*3 carriers (p < 0.05) than in Hispanic, Chinese, Japanese and African samples, (ii) ALDH3A1*2 carriers (p < 0.01) than Caucasian, Hispanic, Chinese, Japanese and African samples. For ABC transporters, a higher frequency of variant allele was observed in (iii) ABCB1 2677 G>T/A (p < 0.01) than Caucasian, Hispanic and African, (iv) ABCB1 3435 C>T (p < 0.05) than Chinese, Japanese and African, (v) ABCC2 1249 G>A (p < 0.01) than Hispanic, Chinese and Japanese samples. In conclusion, cyclophosphamide activation and detoxification of reactive intermediates may be altered in the Pakistani. Though carriers of CYP2C19*2 were higher than in Caucasian and Hispanics, they did not reach statistical significance (p = 0.05).

Objective: Present study was carried out to evaluate acute and subacute hepatotoxicity of Trichodesma indicum (whole plant). Methods: Toxicity study of Trichodesma indicum was carried out in Swiss mice after ingestion of the aqueous methanolic extract, during one day (acute toxicity) and after fifteen days (subacute toxicity). Results: The results showed that the LD50 of the extract was higher than 4000 mg/kg and subacute treatment showed no change in weight of the liver and ALT, ALP, AST, no marked effect on bilirubin, albumin, protein decreased and globulin values increased significantly. Histopathological studies also showed necrosis and excessive vacuolation in maximum dose. Conclusion: So, the extract showed a ladder like dose related hepatotoxicity. This showed that liver function showed mild injury by Trichodesma indicum in this study.

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This is the first article of its type to describe the advances taking place in clinical pharmacy education in Pakistan. The Pharmacy Council of Pakistan has developed a five-year Pharm.D program to replace the four-year B.Pharm degree. Completing clinical pharmacy clerkships is a prerequisite for receiving the Pharm.D degree. To meet this requirement, Ziauddin College of Pharmacy has developed a specialized clerkship program for its 4th and 5th year students. The College is fortunate to be linked with well developed tertiary care hospitals at three prime locations in the in the metropolitan city of Karachi, which provides opportunity for the students to gain exposure to real life situations and work with patients. The article presents an account of the efforts taken for development of the clinical pharmacy clerkship program, the problems encountered during its development, and the main outcomes of a clerkship program.   Type: Note