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The Impact of Drug-Nicotine Interactions on Smoking-Related Outcomes
The Impact of Drug-Nicotine Interactions on Smoking-Related Outcomes
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20260202104815
- ISBN
- 9798293802999
- DDC
- 614.4
- 서명/저자
- The Impact of Drug-Nicotine Interactions on Smoking-Related Outcomes
- 발행사항
- [Sl] : University of Pennsylvania, 2025
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2025
- 형태사항
- 100 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 87-03, Section: B.
- 주기사항
- Advisor: Gross, Robert.
- 학위논문주기
- Thesis (Ph.D.)--University of Pennsylvania, 2025.
- 초록/해제
- 요약Nicotine metabolism is a modifiable risk factor that is associated with several smoking-related outcomes, including smoking cessation rates and being a current smoker. Nicotine is primarily metabolized by the CYP2A6 liver enzyme. Medications that interact with nicotine by altering CYP2A6 activity may change how nicotine is metabolized and thus subsequent smoking outcomes. In this dissertation we study the effects of two CYP2A6 medications, namely efavirenz and nifedipine. In Chapter 2, we measured the changes in nicotine metabolism (represented as the nicotine metabolite ratio, NMR) after efavirenz (a CYP2A6 inducer) was discontinued in a virally suppressed cohort with HIV. The mean NMR difference was −0.24 (SD: 0.37, p0.001), which is more than double a clinically significant change. In Chapter 3, we developed and validated several probabilistic models for smoking status based on cotinine lab assessments to facilitate future studies that require the identification of a smoking cohort. The best performing model was fit using logistic regression, which had acceptable discrimination (AUC= 0.77, 95%CI: 0.75-0.78) and calibration, and was found to be highly specific at many cutoff thresholds. In Chapter 4, we employed a new user, active comparator design to measure the change in the probability of being a current smoker, comparing nifedipine (a CYP2A6 substrate) to amlodipine (not a CYP2A6 substrate). Nifedipine users had slightly larger decreases in smoking status probability changes, with a difference in difference of -0.2% (95% CI: -0.3%, -0.2%). However, in a sub-analysis of individuals with a high probability of being a current smoker at baseline, no differences in the change of probabilities were between the study medications. The results of this dissertation advance the understanding of drug interactions with nicotine and generate tools to facilitate future smoking-related research in real-world data sources.
- 일반주제명
- Epidemiology
- 일반주제명
- Pharmacology
- 일반주제명
- Medicine
- 일반주제명
- Biochemistry
- 일반주제명
- Clinical psychology
- 키워드
- Smoking outcomes
- 기타저자
- University of Pennsylvania Epidemiology and Biostatistics
- 기본자료저록
- Dissertations Abstracts International. 87-03B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■020 ▼a9798293802999
■035 ▼a(MiAaPQ)AAI32168143
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a614.4
■1001 ▼aMedaglio, Dominique.
■24510▼aThe Impact of Drug-Nicotine Interactions on Smoking-Related Outcomes
■260 ▼a[Sl]▼bUniversity of Pennsylvania▼c2025
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2025
■300 ▼a100 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 87-03, Section: B.
■500 ▼aAdvisor: Gross, Robert.
■5021 ▼aThesis (Ph.D.)--University of Pennsylvania, 2025.
■520 ▼aNicotine metabolism is a modifiable risk factor that is associated with several smoking-related outcomes, including smoking cessation rates and being a current smoker. Nicotine is primarily metabolized by the CYP2A6 liver enzyme. Medications that interact with nicotine by altering CYP2A6 activity may change how nicotine is metabolized and thus subsequent smoking outcomes. In this dissertation we study the effects of two CYP2A6 medications, namely efavirenz and nifedipine. In Chapter 2, we measured the changes in nicotine metabolism (represented as the nicotine metabolite ratio, NMR) after efavirenz (a CYP2A6 inducer) was discontinued in a virally suppressed cohort with HIV. The mean NMR difference was −0.24 (SD: 0.37, p0.001), which is more than double a clinically significant change. In Chapter 3, we developed and validated several probabilistic models for smoking status based on cotinine lab assessments to facilitate future studies that require the identification of a smoking cohort. The best performing model was fit using logistic regression, which had acceptable discrimination (AUC= 0.77, 95%CI: 0.75-0.78) and calibration, and was found to be highly specific at many cutoff thresholds. In Chapter 4, we employed a new user, active comparator design to measure the change in the probability of being a current smoker, comparing nifedipine (a CYP2A6 substrate) to amlodipine (not a CYP2A6 substrate). Nifedipine users had slightly larger decreases in smoking status probability changes, with a difference in difference of -0.2% (95% CI: -0.3%, -0.2%). However, in a sub-analysis of individuals with a high probability of being a current smoker at baseline, no differences in the change of probabilities were between the study medications. The results of this dissertation advance the understanding of drug interactions with nicotine and generate tools to facilitate future smoking-related research in real-world data sources.
■590 ▼aSchool code: 0175.
■650 4▼aEpidemiology
■650 4▼aPharmacology
■650 4▼aMedicine
■650 4▼aBiochemistry
■650 4▼aClinical psychology
■653 ▼aNicotine metabolism
■653 ▼aProbabilistic models
■653 ▼aLogistic regression
■653 ▼aSmoking outcomes
■653 ▼aDrug interactions
■690 ▼a0766
■690 ▼a0564
■690 ▼a0487
■690 ▼a0622
■690 ▼a0419
■71020▼aUniversity of Pennsylvania▼bEpidemiology and Biostatistics.
■7730 ▼tDissertations Abstracts International▼g87-03B.
■790 ▼a0175
■791 ▼aPh.D.
■792 ▼a2025
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17358961▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
