Population pharmacokinetics of (R)-albuterol and (S)-albuterol in pediatric patients aged 4–11 years with asthma

Maier, Gary; Rubino, Christopher M.; Hsu, Roger; Grasela, Thaddeus H.; Baumgartner, Rudolf

doi:10.1016/j.pupt.2006.05.003

Cited by 17 publications

(17 citation statements)

References 22 publications

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“…These factors are not well understood but could relate to solution formulation, emitted MDI dose, particle size, or local absorption and metabolism differences. Consistent with prior reports 8,11,12 for subjects receiving racemic albuterol HFA, the (S)-albuterol plasma concentration reached at least a 4-fold higher level than the (R)-albuterol plasma concentration. These high levels of (S)-albuterol in the subjects administered racemic albuterol were not associated with impaired bronchodilatory response in this study.…”

Section: Discussionsupporting

confidence: 90%

A cumulative dose study of levalbuterol and racemic albuterol administered by hydrofluoroalkane-134a metered-dose inhaler in asthmatic subjects

Tripp

McVicar

Nair

et al. 2008

Journal of Allergy and Clinical Immunology

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Section: Discussionsupporting

confidence: 90%

A cumulative dose study of levalbuterol and racemic albuterol administered by hydrofluoroalkane-134a metered-dose inhaler in asthmatic subjects

Tripp

McVicar

Nair

et al. 2008

Journal of Allergy and Clinical Immunology

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“…Some patient or disease characteristics, e.g., weight, renal function, and FEV 1 , may alter dose–concentration relationships. Modeling approaches have been used to characterize the pharmacokinetics of inhalation solutions for use in nebulizers or aerosols (e.g., (R)‐albuterol and (S)‐albuterol inhalation solutions in pediatric patients with asthma, 19 levofloxacin inhalation solution for patients with CF) 20…”

Section: Discussionmentioning

confidence: 99%

Population Pharmacokinetics of Inhaled Tobramycin Powder in Cystic Fibrosis Patients

Ting

Aksenov

Bhansali

et al. 2014

CPT Pharmacom & Syst Pharma

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Tobramycin powder for inhalation (TOBI Podhaler or TIP) is approved for the treatment of Pseudomonas aeruginosa airway infection in patients with cystic fibrosis (CF). A population pharmacokinetic model for tobramycin inhalation powder (TIP) in CF patients was developed to characterize the effect of covariates including body mass index (BMI) and lung function (forced expiratory volume in 1 s as percent of the predicted value (FEV1% predicted) at baseline) on the serum exposure parameters.A two-compartment model with first-order elimination and first-order absorption was developed. Across a range of baseline demographic values in the study population, the predicted mean values for the maximum (Cmax) and trough (Ctrough) plasma concentrations at steady state were at least 7.5 and 5-fold lower, respectively, than the recommended thresholds for tobramycin toxicity (12 µg/ml for Cmax and 2 µg/ml for Ctrough). This model adequately described the tobramycin serum concentration–time course in CF patients following inhalation of TIP. The results indicate that no BMI- or FEV1-based dose adjustment is needed for use of TIP in CF patients.

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“…For instance, empirical models describing the PK of inhaled corticosteroids (ICS), namely ciclesonide (and its active metabolite) (61)(62)(63), budesonide (64,65), fluticasone proprionate (63, 65-67) implemented a single absorption process. Other models based only on inhalation data described the PK of albuterol (68,69), formoterol (70), indacaterol (71), PF-00610355, β 2 -adrenoceptor agonist, (72), zanamivir (73), laninamivir octanoate, prodrug transformed in the lung, and its active form laninamivir (74), GLP-1 (75), tobramycin (76), and HMR1031, VLA-4 antagonist (77) characterized the absorption by the same models. The single absorption process was implemented as a first-order (62-66, 68, 73-77) or a zero-order absorption process (67,69).…”

Section: Empirical Pk Models Based On Inhalation Data Onlymentioning

confidence: 99%

“…Other models based only on inhalation data described the PK of albuterol (68,69), formoterol (70), indacaterol (71), PF-00610355, β 2 -adrenoceptor agonist, (72), zanamivir (73), laninamivir octanoate, prodrug transformed in the lung, and its active form laninamivir (74), GLP-1 (75), tobramycin (76), and HMR1031, VLA-4 antagonist (77) characterized the absorption by the same models. The single absorption process was implemented as a first-order (62-66, 68, 73-77) or a zero-order absorption process (67,69). Variations of model type I included the absorption process being implemented as an IV bolus input or as a fixed high first-order absorption rate constant (62,65), as the available PK data did not allow .…”

Section: Empirical Pk Models Based On Inhalation Data Onlymentioning

confidence: 99%

Pharmacometric Models for Characterizing the Pharmacokinetics of Orally Inhaled Drugs

Borghardt

Weber

Staab

et al. 2015

AAPS J

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Abstract. During the last decades, the importance of modeling and simulation in clinical drug development, with the goal to qualitatively and quantitatively assess and understand mechanisms of pharmacokinetic processes, has strongly increased. However, this increase could not equally be observed for orally inhaled drugs. The objectives of this review are to understand the reasons for this gap and to demonstrate the opportunities that mathematical modeling of pharmacokinetics of orally inhaled drugs offers. To achieve these objectives, this review (i) discusses pulmonary physiological processes and their impact on the pharmacokinetics after drug inhalation, (ii) provides a comprehensive overview of published pharmacokinetic models, (iii) categorizes these models into physiologically based pharmacokinetic (PBPK) and (clinical data-derived) empirical models, (iv) explores both their (mechanistic) plausibility, and (v) addresses critical aspects of different pharmacometric approaches pertinent for drug inhalation. In summary, pulmonary deposition, dissolution, and absorption are highly complex processes and may represent the major challenge for modeling and simulation of PK after oral drug inhalation. Challenges in relating systemic pharmacokinetics with pulmonary efficacy may be another factor contributing to the limited number of existing pharmacokinetic models for orally inhaled drugs. Investigations comprising in vitro experiments, clinical studies, and more sophisticated mathematical approaches are considered to be necessary for elucidating these highly complex pulmonary processes. With this additional knowledge, the PBPK approach might gain additional attractiveness. Currently, (semi-)mechanistic modeling offers an alternative to generate and investigate hypotheses and to more mechanistically understand the pulmonary and systemic pharmacokinetics after oral drug inhalation including the impact of pulmonary diseases.

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Population pharmacokinetics of (R)-albuterol and (S)-albuterol in pediatric patients aged 4–11 years with asthma

Cited by 17 publications

References 22 publications

A cumulative dose study of levalbuterol and racemic albuterol administered by hydrofluoroalkane-134a metered-dose inhaler in asthmatic subjects

A cumulative dose study of levalbuterol and racemic albuterol administered by hydrofluoroalkane-134a metered-dose inhaler in asthmatic subjects

Population Pharmacokinetics of Inhaled Tobramycin Powder in Cystic Fibrosis Patients

Pharmacometric Models for Characterizing the Pharmacokinetics of Orally Inhaled Drugs

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