I= ENVIRONMENTAL AND GEONETICAL CONSIDERATIONS IN THE EVALUATION OF DOSAGE REGIM FOR DRUGS FOR THE LOCAL POPULATION WITH SPECIAL REFERENCES TO ACETYLATOR STATUS, DRUG METABOLISM AND PHENOTYPING
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Title of Thesis
ENVIRONMENTAL AND GEONETICAL CONSIDERATIONS IN THE EVALUATION OF DOSAGE REGIM FOR DRUGS FOR THE LOCAL POPULATION WITH SPECIAL REFERENCES TO ACETYLATOR STATUS, DRUG METABOLISM AND PHENOTYPING

Author(s)
Muhammad Aslam
Institute/University/Department Details
Department of Pharmaceutics/ University of Karachi
Session
2004
Subject
Pharmacy
Number of Pages
162
Keywords (Extracted from title, table of contents and abstract of thesis)
dosage regime, acetylator status, drug metabolism, phenotyping, enzyme system, drug, drug metabolizing enzymes (dme), genome

Abstract
In the Phase-II enzyme system, N-acetylator involved in the detoxification pathways for certain drug, xenophobic and diety and environmental chemicals, has been found polymorphic in various population.

Acetylator phenotyping and genotyping of NAT2 in the Pakistan population has been studied. Sulfadimidine was used as a Marker drug and through the analysis of free drug (SDM) and its metabolite (N4-SDM) Biopharmaceutic characteristics and Pharmacokinetic parameters were determined in the local subjects. Optimum sampling procedure for population phenotyping study was also determined. Biopharmaceutic characteristic were used to evaluate phenotyping in the population that showed a bimodal 55:52 ratio for fast and slow acetylators, respectively, in the Pakistan population.

NA T2 genotyping was done in the patient, hospital control and normal population control groups, using a PCR-RFLP method. Phenotyping and genotyping were closely related and a good concordance was found. Bladder cancer patients showed about a 2 fold increase in slow acetylator, compared to the population control. Occupational exposure and smoking association were also studied.

Epidemiological studies under the local environmental and geographical conditions would help to evaluate the genetic-environmental variability for appropriate dosage for drugs, to avoid adverse drug reaction, and to save guard against cancers and associated risk through behavior, lifestyle and social determinants of health.

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1827.77 KB
S. No. Chapter Title of the Chapters Page Size (KB)
1 0 Contents 0
114.06 KB
2 1 Literature Review 3
664.83 KB
  1.1 Population Genetics 19
  1.2 The Human Genome 25
  1.3 Drug Metabolism 30
  1.4 Drug Metabolizing Enzymes (Dme) 36
  1.5 Detection Of Variability In Drug Metabolism Using Pharamacogenetics Tools 47
  1.6 Pharmacogenetics Of N- Acetylation 50
3 2 Medical Implication Of N-Acetyl Transferase 75
228.87 KB
  2.1 Phenotypes In Drug Acetylation (Metabolism) 86
  2.2 Sulfonamides 92
4 3 Materials And Apparatus 103
155.72 KB
  3.1 Estimation Of Free Sulfadimidine And N 4 -Acetyl Sulfadimidine In Body Fluids Choices Of The Analytical Technique 109
5 4 Results And Discussion 121
168.2 KB
6 5 Conclusion 139
466.28 KB
  5.1 Appendix 139
7 6 References 142
255.15 KB