Pakistan Research Repository

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

Muhammad, Aslam (2004) 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. PhD thesis, University of Karachi, Karachi.

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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.

Item Type:Thesis (PhD)
Uncontrolled Keywords:dosage regime, acetylator status, drug metabolism, phenotyping, enzyme system, drug, drug metabolizing enzymes (dme), genome
Subjects:Biological & Medical Sciences (c) > Medical Sciences (c2) > Pharmacy(c2.5)
ID Code:1133
Deposited By:Mr. Muhammad Asif
Deposited On:03 Jan 2007
Last Modified:04 Oct 2007 21:04

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