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Effect of smoking on the pharmacokinetics of inhaled loxapine.

Takahashi LH, Huie K, Spyker DA, Fishman RS, Cassella JV - Ther Drug Monit (2014)

Bottom Line: Loxapine Cmax was similar in smokers and nonsmokers with a GMR of 99.0%.A slight decrease in the observed mean terminal half-life values was observed for smokers (6.52 hours for smokers and 7.30 hours for nonsmokers).It was concluded that inhaled loxapine does not require dosage adjustment based on smoking behavior.

View Article: PubMed Central - PubMed

Affiliation: *Alexza Pharmaceuticals, Inc, Mountain View; and †Intermune, Inc, Brisbane, California.

ABSTRACT

Background: Loxapine inhalation powder delivered by a hand-held device as a thermally generated aerosol (ADASUVE) was recently approved in the United States and European Union for use in the acute treatment of agitation in patients with bipolar disorder or schizophrenia. As smokers comprise a large subpopulation of these patients, and many antipsychotic drugs require dose adjustments for smokers, the objective of this study was to compare the pharmacokinetics of inhaled loxapine administered to smokers and nonsmokers.

Methods: Pharmacokinetics and sedation pharmacodynamics using a visual analog scale were studied in 35 male and female adult subjects (18 nonsmokers and 17 smokers) following a single dose of 10 mg of inhaled loxapine. Blood samples were drawn at predose, 30 seconds, 1, 2, 3, 10, 30, and 60 minutes, and 2, 6, 12, and 24 hours after dosing. Loxapine and 8-OH-loxapine were analyzed using reverse-phase liquid chromatography coupled with a tandem mass spectrometer. Pharmacokinetic parameters assessed included Cmax, Tmax, AUCinf, and T1/2 for loxapine and 8-OH-loxapine. Geometric mean ratios (GMRs) were determined for smokers to nonsmokers.

Results: Loxapine Cmax was similar in smokers and nonsmokers with a GMR of 99.0%. The median loxapine Tmax was 1.88 and 1.01 minutes for nonsmokers and smokers, respectively. Loxapine AUCinf and AUClast values in nonsmokers were comparable with smokers (GMRs of 85.3% and 86.7%, respectively). A slight decrease in the observed mean terminal half-life values was observed for smokers (6.52 hours for smokers and 7.30 hours for nonsmokers).

Conclusions: Sedation profiles and visual analog scale scores at each time point were similar for nonsmokers and smokers. It was concluded that inhaled loxapine does not require dosage adjustment based on smoking behavior.

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Related in: MedlinePlus

Mean loxapine and 8-OH-loxapine plasma concentration (in nanogram per milliliter) (90% CI) versus time postdose (in hours) by smoking status; log scale (PK population).
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Related In: Results  -  Collection


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Figure 1: Mean loxapine and 8-OH-loxapine plasma concentration (in nanogram per milliliter) (90% CI) versus time postdose (in hours) by smoking status; log scale (PK population).

Mentions: The pharmacokinetics of loxapine and its main metabolite, 8-OH-loxapine, in smokers and nonsmokers after administration of a 10 mg dose of inhaled loxapine is shown in Figure 1 and the PK parameters for loxapine and 8-OH-loxapine are listed in Tables 2 and 3, respectively.


Effect of smoking on the pharmacokinetics of inhaled loxapine.

Takahashi LH, Huie K, Spyker DA, Fishman RS, Cassella JV - Ther Drug Monit (2014)

Mean loxapine and 8-OH-loxapine plasma concentration (in nanogram per milliliter) (90% CI) versus time postdose (in hours) by smoking status; log scale (PK population).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4218760&req=5

Figure 1: Mean loxapine and 8-OH-loxapine plasma concentration (in nanogram per milliliter) (90% CI) versus time postdose (in hours) by smoking status; log scale (PK population).
Mentions: The pharmacokinetics of loxapine and its main metabolite, 8-OH-loxapine, in smokers and nonsmokers after administration of a 10 mg dose of inhaled loxapine is shown in Figure 1 and the PK parameters for loxapine and 8-OH-loxapine are listed in Tables 2 and 3, respectively.

Bottom Line: Loxapine Cmax was similar in smokers and nonsmokers with a GMR of 99.0%.A slight decrease in the observed mean terminal half-life values was observed for smokers (6.52 hours for smokers and 7.30 hours for nonsmokers).It was concluded that inhaled loxapine does not require dosage adjustment based on smoking behavior.

View Article: PubMed Central - PubMed

Affiliation: *Alexza Pharmaceuticals, Inc, Mountain View; and †Intermune, Inc, Brisbane, California.

ABSTRACT

Background: Loxapine inhalation powder delivered by a hand-held device as a thermally generated aerosol (ADASUVE) was recently approved in the United States and European Union for use in the acute treatment of agitation in patients with bipolar disorder or schizophrenia. As smokers comprise a large subpopulation of these patients, and many antipsychotic drugs require dose adjustments for smokers, the objective of this study was to compare the pharmacokinetics of inhaled loxapine administered to smokers and nonsmokers.

Methods: Pharmacokinetics and sedation pharmacodynamics using a visual analog scale were studied in 35 male and female adult subjects (18 nonsmokers and 17 smokers) following a single dose of 10 mg of inhaled loxapine. Blood samples were drawn at predose, 30 seconds, 1, 2, 3, 10, 30, and 60 minutes, and 2, 6, 12, and 24 hours after dosing. Loxapine and 8-OH-loxapine were analyzed using reverse-phase liquid chromatography coupled with a tandem mass spectrometer. Pharmacokinetic parameters assessed included Cmax, Tmax, AUCinf, and T1/2 for loxapine and 8-OH-loxapine. Geometric mean ratios (GMRs) were determined for smokers to nonsmokers.

Results: Loxapine Cmax was similar in smokers and nonsmokers with a GMR of 99.0%. The median loxapine Tmax was 1.88 and 1.01 minutes for nonsmokers and smokers, respectively. Loxapine AUCinf and AUClast values in nonsmokers were comparable with smokers (GMRs of 85.3% and 86.7%, respectively). A slight decrease in the observed mean terminal half-life values was observed for smokers (6.52 hours for smokers and 7.30 hours for nonsmokers).

Conclusions: Sedation profiles and visual analog scale scores at each time point were similar for nonsmokers and smokers. It was concluded that inhaled loxapine does not require dosage adjustment based on smoking behavior.

Show MeSH
Related in: MedlinePlus