Effect of active and passive cigarette smoking on CYP1A2-mediated phenacetin disposition in Chinese subjects

S. Xiao Dong, Z. Zhi Ping, W. Zhong Xiao, C. Chong Shu, A. Bartoli, G. Gatti, S. D'Urso, Emilio Perucca

Research output: Contribution to journalArticlepeer-review

Abstract

The effect of active and passive cigarette smoking on CYP1A2-mediated phenacetin disposition was evaluated in a controlled study of 36 healthy Chinese subjects. Each subject was administered a single oral dose of phenacetin (900 mg), and frequent blood samples were taken for up to 12 hours for simultaneous high-pressure liquid chromatography determinations of plasma concentrations of phenacetin and metabolically derived paracetamol. Compared with values observed in controls not exposed to cigarette smoking, subjects who smoked 7 to 40 (median, 20) cigarettes per day exhibited a 2.5-fold higher phenacetin apparent oral clearance (7.2, 4.3-12.0 L.h-1.kg-1 vs 2.9, 1.8-4.6 L.h-1.kg-1 [geometric means, 95% confidence intervals]; n = 12, p <0.05). In subjects exposed to passive smoking, phenacetin's apparent oral clearance (3.6, 2.0-6.6 L.h-1.kg-1, n = 12) was intermediate between the values observed in the two other groups. Plasma paracetamol levels were moderately lower in active smokers than in passive smokers and controls. These results demonstrated that, in contrast to results found in previous studies, Chinese subjects were fully susceptible to the inducing effect of cigarette smoke on CYP1A2 activity.

Original languageEnglish
Pages (from-to)371-375
Number of pages5
JournalTherapeutic Drug Monitoring
Volume20
Issue number4
DOIs
Publication statusPublished - Aug 1998

Keywords

  • Cigarette smoking
  • Cytochrome CYP1A2
  • Enzyme induction
  • Ethnopharmacology
  • Paracetamol
  • Phenacetin

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Health, Toxicology and Mutagenesis
  • Pharmacology (medical)
  • Public Health, Environmental and Occupational Health
  • Pharmacology
  • Toxicology

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