Role of tobacco smoking in pharmacokinetics

1 The independent as well as interactive effects of chronic (> 6 months) oral contraceptive (OC) use and cigarette smoking on single-dose (4 mg/kg) theophylline disposition were assessed in 49 young, healthy women. 2 Significant elevations (40%) in theophylline plasma clearance were found in women who smoked. OC use resulted in decreases in clearance of a similar magnitude (28%). These factors do not appear to interact with respect to theophylline disposition. The combination of main effects tended to cancel one another (clearance of49.1 ml h-I kg-'ideal body weight for OC non-user, non-smoker, vs 49.7 ml h-' kg-'for OC user-smoker). 3 Single dose exposure to OC in non-users did not significantly alter theophylline pharmacokinetics for the group as a whole. However, in the subgroup of smoking subjects, significant decreases in clearance were evident (P < 0.05). Analogous results were found for half-life. Volume of distribution was slightly diminished in smokers, but was unaffected in OC users.4 Areas under the serum concentration-time (AUC) profiles of norgestrel and ethinyloestradiol were examined in 27 women as indices of OC exposure. The smallest values of theophylline clearance were found in the subjects with largest AUC of both OC steroids. 5 Appropriate statistical analyses of data which are influenced by multiple factors are discussed.Special concern is needed when the factor partitioning process yields subgroups of unequal sizes.

Section: Primary Smoking and Oc Effectssupporting

confidence: 94%

“…Another ubiquitous source of altered drug elimination is tobacco smoking which seems to cause selective enzyme induction and increased biotransformation rates of some drugs (Jusko, 1978). Marked increases in theophylline clearances are exhibited in some smokers .…”

Section: Introductionmentioning

confidence: 99%

Effects of tobacco smoking and oral contraceptive use on theophylline disposition.

Gardner¹,

Tornatore²,

Wj³

et al. 1983

“…When assessed using other drugs as substrates, three of the principal pathways for quinidine metabolism (aliphatic hydroxylation, aromatic oxidation and O-dealkylation) have been shown to be induced in chronic smokers (Jusko, 1978). Since a history of chronic tobacco use is common among patients being treated with this drug, we examined the effect of cigarette smoking on the clearance and metabolism of quinidine in 14 patients.…”

Section: Introductionmentioning

confidence: 99%

Lack of effect of smoking on the metabolism and pharmacokinetics of quinidine in patients.

Edwards

Axelson

Visco

et al. 1987

The urinary metabolite profile of quinidine and the oral clearance of this drug were studied under steady state conditions in five smoking and nine non-smoking patients. No significant differences were observed in the urinary recovery of unchanged quinidine, 3S-3-hydroxyquinidine, 2'-oxoquinidinone or quinidine-N-oxide between smokers and non-smokers. In addition, the plasma clearance of quinidine was not affected by the smoking status of subjects. These results suggest that cigarette smoke does not induce any of the main pathways for quinidine metabolism in a typical patient population and that the consideration of smoking status is of little utility in aiding in the selection of initial dosage regimens for this drug.

“…There are indications that the rate of metabolism of all drugs that are oxidized is not increased to the same extent. It has, for example, been demonstrated that the rate of oxidation of a large number of drugs is increased by cigarette smoking whereas the rate of metabolism of various other drugs is unchanged (Jusko, 1978(Jusko, , 1979. Also following treatment with enzyme-inducing drugs, the degree of stimulation of metabolism of certain compounds may differ considerably one from another.…”

Section: Introductionmentioning

confidence: 99%

Differential effects of enzyme induction on antipyrine metabolite formation.

Danhof¹,

Verbeek²,

Boxtel³

et al. 1982

1 The influence of enzyme induction with antipyrine and pentobarbitone was studied on the rates of formation of the major metabolites of antipyrine: 4-hydroxyantipyrine, norantipyrine and 3-hydroxymethyl-antipyrine + 3-carboxy-antipyrine. The inducing drugs were given to panels of healthy volunteers for 8 days and prior to and after this period antipyrine total elimination clearance was determined in plasma, whereas the partial clearances for production of the individual metabolites were assessed on the basis of urinary excretion data. 2 Antipyrine total clearance had significantly increased by 16% following treatment with antipyrine, which could almost entirely be attributed to a selective increase in the rate of production of norantipyrine. 3 With pentobarbitone total clearance of antipyrine had increased by 60%, which was associated with a significant increase in the clearance of production of all three metabolites. However, the increase in norantipyrine formation was significantly higher than the increase in 4-hydroxyantipyrine and 3-hydroxymethyl-antipyrine formation. 4 The most likely explanation for these differences in the degree of induction of the different metabolic routes of antipyrine, is that different enzymes are involved in the different routes. Apparently the enzyme involved in norantipyrine formation is most sensitive to induction by antipyrine and pentobarbitone. By measuring rates of antipyrine metabolite formation it may be possible to study the degree of selectivity of enzyme inducers on oxidative drug metabolism.