Prediction of drug clearance in a smoking population: modeling the impact of variable cigarette consumption on the induction of CYP1A2

Plowchalk, David R.; Yeo, Karen Rowland

doi:10.1007/s00228-011-1189-y

Cited by 51 publications

(42 citation statements)

References 31 publications

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“…It has been suggested that the smoking-induced changes in hepatic CYP1A2 abundance are dependent on the daily cigarette consumption 51. Therefore, the differences in the amounts of smoking might have contributed to the variations in the influence of cigarette smoking on the disposition of olanzapine and clozapine among the studies included.…”

Section: Discussionmentioning

confidence: 99%

Meta-analysis: the effects of smoking on the disposition of two commonly used antipsychotic agents, olanzapine and clozapine

2014

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ObjectiveTo clarify the effects of smoking on the disposition of two commonly used antipsychotics, olanzapine and clozapine, and to create standards to adjust the doses of these drugs in clinical practice based on the smoking status.DesignA meta-analysis was conducted by searching MEDLINE, Scopus and the Cochrane Library for relevant prospective and retrospective studies.Included studiesWe included the studies that investigated the effects of smoking on the concentration to dose (C/D) ratio of olanzapine or clozapine.Primary outcome measureThe weighted mean difference was calculated using a DerSimonian-Laird random effects model, along with 95% CI.ResultsSeven association studies, comprising 1094 patients (652 smokers and 442 non-smokers) with schizophrenia or other psychiatric disorders, were included in the meta-analysis of olanzapine. The C/D ratio was significantly lower in smokers than in non-smokers (p<0.00001), and the mean difference was −0.75 (ng/mL)/(mg/day) (95% CI −0.89 to −0.61). Therefore, it was estimated that if 10 and 20 mg/day of olanzapine would be administered to smokers, about 7 and 14 mg/day, respectively, should be administered to non-smokers in order to obtain the equivalent olanzapine concentration. Four association studies of clozapine were included in the meta-analysis of clozapine, comprising 196 patients (120 smokers and 76 non-smokers) with schizophrenia or other psychiatric disorders. The C/D ratio was significantly lower in smokers than in non-smokers (p<0.00001), and the mean difference was −1.11 (ng/mL)/(mg/day) (95% CI −1.53 to −0.70). Therefore, it was estimated that if 200 and 400 mg/day of clozapine would be administered to smokers, about 100 and 200 mg/day, respectively, should be administered to non-smokers.ConclusionsWe suggest that the doses of olanzapine and clozapine should be reduced by 30% and 50%, respectively, in non-smokers compared with smokers in order to obtain an equivalent olanzapine or clozapine concentration.

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Section: Discussionmentioning

confidence: 99%

Meta-analysis: the effects of smoking on the disposition of two commonly used antipsychotic agents, olanzapine and clozapine

2014

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“…Simulations were performed in healthy subjects (n = 100, 50% men, aged 40-65 years). A population of smokers was constructed by modifying the CYP1A2 abundance in healthy subjects from 52 to 94 pmol/mg microsomal protein to mimic individuals who smoke .20 cigarettes per day (Plowchalk and Rowland Yeo, 2012). The Simcyp default phenacetin profile was used without further modification.…”

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confidence: 99%

Identification and Characterization of Psoralen and Isopsoralen as Potent CYP1A2 Reversible and Time-Dependent Inhibitors in Human and Rat Preclinical Studies

Zhuang

Zhong

Xiao

et al. 2013

Drug Metabolism and Disposition

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Naturally occurring furanocoumarin compounds psoralen (PRN) and isopsoralen (IPRN) are bioactive constituents found in herbaceous plants. They are widely used as active ingredients in several Chinese herbal medicines. In this study, the CYP1A2 inhibitory potential of PRN and IPRN was investigated in rats in vitro and in vivo as well as in human liver microsomes. Both compounds exhibited reversible and time-dependent inhibition toward rat microsomal cyp1a2. The IC 50 , k inact , and K I values were 10.4 6 1.4 mM, 0.060 6 0.002 min 21 , and 1.13 6 0.12 mM for PRN, and 7.1 6 0.6 mM, 0.10 6 0.01 min 21 , and 1.95 6 0.31 mM for IPRN, respectively. In human liver microsomal incubations, potent reversible CYP1A2 inhibition was observed for both compounds, with IC 50 values of 0.26 6 0.01 mM and 0.22 6 0.03 mM for PRN and IPRN, respectively. However, time-dependent inhibition was only observed for IPRN, with k inact and K I values of 0.050 6 0.002 min 21 and 0.40 6 0.06 mM, respectively. Coadministration with PRN or IPRN significantly inhibited cyp1a2 activity in rats, with the area under the curve (AUC) of phenacetin increasing more than 5-fold. Simcyp simulation predicted that PRN would cause 1.71-and 2.12-fold increases in the phenacetin AUC in healthy volunteers and smokers, respectively. IPRN, on the other hand, would result in 3.24-and 5.01-fold increases in phenacetin AUCs in healthy volunteers and smokers, respectively. These findings represent the first detailed report comparing the potential drug-drug interactions of PRN and IPRN, and provide useful information for balancing safe and efficacious doses of PRN and IPRN.

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“…Numerous endogenous and exogenous compounds, including drugs, were metabolized by CYP enzymes (26). CYP could be subdivided to many isoforms; CYP1A2 is one of the major P450 isoforms, contributing nearly 20% of the hepatic P450 pool and catalyzing oxidative biotransformation of various types of commonly used drugs such as theophylline, caffeine, and clozapine (1,2,27). The activity of hepatic CYP enzymes can be regulated b y s e v e r a l e n d o g e n o u s a n d e x o g e n o u s f a c t o r s .…”

Section: Discussionmentioning

confidence: 99%

“…Many drugs, such as theophylline, warfarin, and caffeine are metabolized by hepatic CYP1A2 (1,2). Many factors can influence the activity of hepatic CYP.…”

Section: Introductionmentioning

confidence: 99%

Decreased expression of hepatic cytochrome P450 1A2 (CYP1A2) in a chronic intermittent hypoxia mouse model

et al. 2018

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Background: Hepatic cytochrome P450 (CYP) isoforms, CYP1A2, is one of important enzymes for many drugs metabolism. Studies have confirmed that sustained hypoxia can influence the expression of hepatic CYP, including CYP1A2. The impact of chronic intermittent hypoxia (CIH), a marked characteristic of sleep apnea, on CYP1A2 remains unclear. The aim of the present study was to evaluate the effect of CIH on the expression of hepatic CYP1A2 in a mouse model with sleep apnea.Methods: Twenty four old male (6-8 weeks) C57BL/6J mice (n=12 in each group) were randomly assigned to either normoxia group or CIH group. Mice in CIH group underwent 12 weeks intermittent hypoxia exposure. The different gene expression of hepatic CYP1A2 between two groups was analyzed by quantity real-time polymerase chain reaction. The protein levels of hepatic CYP1A2 in each group were observed by using western blotting and immunohistochemistry.Results: After 12 weeks of exposure to intermittent hypoxia, the expression of hepatic CYP1A2, at the mRNA and protein levels was decreased more significantly in the CIH group than the normoxia group (P<0.01).Conclusions: CIH contributes to inhibiting the expression of hepatic CYP1A2. This implies that the dosage of drugs metabolized by CYP1A2, should be adjusted in patients with sleep apnea.

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Prediction of drug clearance in a smoking population: modeling the impact of variable cigarette consumption on the induction of CYP1A2

Abstract: This study demonstrates that it may be possible to predict the clearance of CYP1A2 substrates in smoking populations using quantitative estimates of CYP1A2 abundance based on daily cigarette consumption in conjunction with an IVIVE approach.

Cited by 51 publications

References 31 publications

Meta-analysis: the effects of smoking on the disposition of two commonly used antipsychotic agents, olanzapine and clozapine

Meta-analysis: the effects of smoking on the disposition of two commonly used antipsychotic agents, olanzapine and clozapine

Identification and Characterization of Psoralen and Isopsoralen as Potent CYP1A2 Reversible and Time-Dependent Inhibitors in Human and Rat Preclinical Studies

Decreased expression of hepatic cytochrome P450 1A2 (CYP1A2) in a chronic intermittent hypoxia mouse model

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