Disposition of oxazepam in relation to age, sex, and cigarette smoking

Ochs, HR; Greenblatt, David J.; Otten, H.

doi:10.1007/bf01721923

Cited by 42 publications

(26 citation statements)

References 22 publications

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“…Bock et al [1987] found an increased urinary ex cretion ratio of intact acetaminophen di vided by acetaminophen metabolites, but the plasma clearance of acetaminophen was not evaluated. The benzodiazepine deriva tives, oxazepam and lorazepam, are biotransformed mainly by glucuronide conjuga tion , Ochs et al [1981] found significantly enhanced clearance of oxazepam among cigarette smokers, but this was not true for lorazepam [Ochs et al, 1985],…”

Section: Discussionmentioning

confidence: 95%

Differential Effect of Cigarette Smoking on Antipyrine Oxidation versus Acetaminophen Conjugation

et al. 1990

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The effect of cigarette smoking on drug oxidation and conjugation was studied using antipyrine and acetaminophen as marker compounds. For the antipyrine study, healthy cigarette smokers (n = 30) and nonsmoking controls (n = 53) received a single 1.0-gram intravenous dose of antipyrine. For the acetaminophen study, 14 smokers and 15 nonsmokers received a 650-mg intravenous dose of acetaminophen. The clearance of antipyrine was significantly increased (0.93 vs. 0.60 ml/min/kg, p < 0.0001) and elimination half-life was correspondingly reduced (8.9 vs. 13.0 h, p < 0.0001) in smokers compared to nonsmoking controls. Total recovery of antipyrine and metabolites excreted in urine did not differ between groups, but there was a significantly increased fractional clearance of antipyrine via formation of 4-hydroxyantipyrine and 3-hydroxymethyl metabolites in smokers. Fractional clearance via formation of norantipyrine did not differ significantly between groups. Comparison of acetaminophen kinetics between smokers and nonsmokers indicated no significant differences in elimination half-life, clearance or volume of distribution. Thus, cigarette smoking is more likely to induce drug oxidation rather than drug conjugation. However, not all oxidative pathways are equally influenced; induction effects of smoking are highly substrate selective and pathway specific.

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Section: Discussionmentioning

confidence: 95%

Differential Effect of Cigarette Smoking on Antipyrine Oxidation versus Acetaminophen Conjugation

et al. 1990

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“…Dragacci et al showed no effect of smoking on bilirubin (UGT1A1) or clofibrate (UGT2B7) glucuronidation in microsomes from liver biopsies (Dragacci et al, 1987). Results from several in vivo studies suggest that the clearance of acetaminophen (Bock et al, 1994; Bock et al, 1987), oxazepam (Ochs et al, 1981), and codeine (Yue et al, 1989; Yue et al, 1994) is higher in cigarette smokers, although the extent of the difference was small and probably clinically unimportant. In contrast, results of several other studies show no effects of smoking on the clearance by glucuronidation of acetaminophen (Miners et al, 1984; Scavone et al, 1990), diflunisal (Macdonald et al, 1990), and lorazepam (Ochs et al, 1985).…”

Section: Interindividual Variability In Activity Of the Major Ugt Isomentioning

confidence: 99%

Interindividual variability in hepatic drug glucuronidation: studies into the role of age, sex, enzyme inducers, and genetic polymorphism using the human liver bank as a model system

Court¹

2009

Drug Metabolism Reviews

182

147

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The human liver bank has provided an invaluable model system for the study of interindividual variability in expression and activity of the major hepatic UGTs, including UGT1A1, 1A4, 1A6, 1A9, 2B7, and 2B15. Based on studies using UGT isoform selective probes, the rank order of activity variability is UGT 1A1 > 1A6 > 2B15 > 1A4 = 1A9 > 2B7 with coefficient of variation values ranging from 92% to 45%. Liver donor age, sex, enzyme inducers, and genetic polymorphism are factors that have been implicated as sources of this variability in UGT activity. The expression of UGTs prior to and immediately following birth is quite limited, explaining the susceptibility of neonates to certain drug toxicities. Old age appears to have minimal effect on UGT function. Sex differences in UGT activity are relatively small and are confined to several UGTs, including UGT2B15, which shows higher activity in males compared with females. Enzyme inducers, including co-administered drugs, smoking, and alcohol may increase hepatic UGT levels. Human liver bank phenotype-genotype studies using UGT isoform-selective probes have identified common genetic polymorphisms that are predictive of glucuronidation activity in vitro that were subsequently verified as predictors of probe drug clearance by glucuronidation in vivo.

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“…Published articles have studied pharmacokinetics of this drug [2][3][4]. There are also reports of tobacco smoke affecting pharmacokinetics of various drugs; Elimination rate was increased in theophylline [5][6][7], imipramine [8], propranolol [9] and oxazpam [10] in smoker subjects. No difference was observed in multiple dose pharmacokinetics of phenobarbital in nonsmokers in comparison with the smokers [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Effect of smoking on single dose pharmacokinetics of phenobarbital

Mirfazaelian¹,

Jahanzad²,

Tabatabaei-far³

et al. 2001

Biopharm & Drug Disp

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In order to determine interaction of smoking with single dose pharmacokinetics of phenobarbital, a 60 mg tablet of the drug was given to 12 healthy male subjects in two groups (6 smokers and 6 non-smokers) in a double blind study. An HPLC method using UV detection was developed to assess phenobarbital in plasma of the subjects. Pharmacokinetic parameters were calculated and compared in the two groups. Pharmacokinetic parameters of the two groups were not significantly different in the two groups (p<0.05). The results show no considerable effect of cigarette smoking on phenobarbital pharmacokinetics, which is in agreement with enzyme studies performed previously.

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Disposition of oxazepam in relation to age, sex, and cigarette smoking

Cited by 42 publications

References 22 publications

Differential Effect of Cigarette Smoking on Antipyrine Oxidation versus Acetaminophen Conjugation

Differential Effect of Cigarette Smoking on Antipyrine Oxidation versus Acetaminophen Conjugation

Interindividual variability in hepatic drug glucuronidation: studies into the role of age, sex, enzyme inducers, and genetic polymorphism using the human liver bank as a model system

Effect of smoking on single dose pharmacokinetics of phenobarbital

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