Pharmacokinetics and Pharmacodynamics of Cumulative Single Doses of Inhaled Salbutamol Enantiomers in Asthmatic Subjects

Gumbhir‐Shah, Kavita; Kellerman, Donald J.; DeGraw, Sidney; Koch, Patrick; Jusko, William J.

doi:10.1006/pupt.1999.0217

Cited by 71 publications

(45 citation statements)

References 25 publications

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“…Because insulin effects were not directly included in the final model, the final parameter estimate for k out might be better interpreted as a combination of exogenous premeal insulin effect and net removal of glucose in the basal state. The k out value is similar to estimated values in healthy individuals (0.011-0.071 min ) (20,(28)(29)(30) and to the estimate in type 2 diabetic patients after an OGTT (0.00861 min…”

Section: Discussionsupporting

confidence: 83%

“…The estimated PD parameters are summarized in Table III. In general, the final estimated parameters controlling glucose turnover are in good agreement with literature values (20)(21)(22)(28)(29)(30)(31)(32). The population mean estimate of baseline glucose concentration was 161 mg/dL and displayed 37.1% variability between occasions.…”

Section: Pharmacodynamic Modelingsupporting

confidence: 85%

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Study Reanalysis Using a Mechanism-Based Pharmacokinetic/Pharmacodynamic Model of Pramlintide in Subjects with Type 1 Diabetes

Fang

Landersdorfer

Cirincione³

et al. 2012

AAPS J

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Abstract. This report describes a pharmacokinetic/pharmacodynamic model for pramlintide, an amylinomimetic, in type 1 diabetes mellitus (T1DM). Plasma glucose and drug concentrations were obtained following bolus and 2-h intravenous infusions of pramlintide at three dose levels or placebo in 25 T1DM subjects during the postprandial period in a crossover study. The original clinical data were reanalyzed by mechanism-based population modeling. Pramlintide pharmacokinetics followed a twocompartment model with zero-order infusion and first-order elimination. Pramlintide lowered overall postprandial plasma glucose AUC (AUC net ) and delayed the time to peak plasma glucose after a meal (T max ). The delay in glucose T max and reduction of AUC net indicate that overall plasma glucose concentrations might be affected by differing mechanisms of action of pramlintide. The observed increase in glucose T max following pramlintide treatment was independent of dose within the studied dose range and was adequately described by a dose-independent, maximum pramlintide effect on gastric emptying of glucose in the model. The inhibition of endogenous glucose production by pramlintide was described using a sigmoidal function with capacity and sensitivity parameter estimates of 0.995 for I max and 23.8 pmol/L for IC 50 . The parameter estimates are in good agreement with literature values and the IC 50 is well within the range of postprandial plasma amylin concentrations in healthy humans, indicating physiological relevance of the pramlintide effect on glucagon secretion in the postprandial state. This model may prove to be useful in future clinical studies of other amylinomimetics or antidiabetic drugs with similar mechanisms of action.

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Section: Discussionsupporting

confidence: 83%

Section: Pharmacodynamic Modelingsupporting

confidence: 85%

Study Reanalysis Using a Mechanism-Based Pharmacokinetic/Pharmacodynamic Model of Pramlintide in Subjects with Type 1 Diabetes

Fang

Landersdorfer

Cirincione³

et al. 2012

AAPS J

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“…(S)-albuterol has a 10-fold slower rate of metabolism than (R)-albuterol and with frequent dosing it can accumulates in patient"s plasma and lung tissue in the absence of (R)-albuterol 19 . Levosalbutamol has approx.…”

Section: Discussionmentioning

confidence: 99%

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2013

IJPSR

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ABSTRACT:Background: β2-agonist drugs are frequently prescribed in asthmatics. Apart from bronchodilation they affect biochemical and physical parameters of the body. Method: Total 80 patients were divided into two groups. Group I (n=40) received Albuterol-2.5mg./2.5ml. TDS and Group II (n=40) received Levalbuterol-0.63mg./2.5ml, TDS via nebulizer for 4 weeks. Baseline and post-treatment estimation of biochemical parameters including, fasting and postprandial plasma glucose levels, serum Na+, serum K+ levels, lipid profile, Monitoring of systolic and diastolic BP and adverse drug effects evaluation were carried out. Results: Significantly changes were in serum lipid profile and blood glucose in both the groups but increase was more in group I. Serum K+ level was decreased significantly (p<0.05) in both groups but decrease was more in group I patients. The fasting and postprandial plasma glucose levels were significantly increased in both the groups but increase was more in group I. Systolic BP increases and diastolic BP decreases after administration of both drugs. There was no significant change observed in Serum Na+ level after administration of both drugs. After administration of both the drugs, an increase was observed in serum Lipid profile level. Adverse drug profile showed that Levalbuterol produce less adverse effects as compare to Albuterol. Conclusion: This study concludes that Levalbuterol is safer and it carries fewer incidences of adverse effects as compare to Albuterol.

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“…27 En el salbutamol similar, la posología está indicada en gotas según edad y peso, y en el salbutamol original, en mg/kg de peso. En nuestro estudio, se empleó una dosis única de salbutamol original y similar y, por lo tanto, no pudo establecerse en qué parte de la curva dosis-respuesta se encuentra la RBD obtenida.…”

Section: Discussionunclassified

Salbutamol original contra salbutamol similar en niños con crisis de asma. Estudio aleatorizado, controlado y doble ciego

et al. 2012

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Arch Argent Pediatr 2012;110(4):285-290 / 285 RESUMEN Introducción. Existe evidencia clínica que sugiere que el salbutamol original sería más eficaz que el salbutamol similar para revertir los síntomas en el episodio agudo de asma. Objetivo. Evaluar la respuesta broncodilatadora de ambas especialidades farmacéuticas de salbutamol en niños con asma y establecer, mediante el volumen espiratorio forzado, si difiere entre los grupos tratados con salbutamol original y similar. Diseño. Estudio prospectivo, aleatorizado, controlado, a doble ciego. Material y métodos. Se incluyeron 126 niños (63 varones, edad 9,18 ± 2,83 años), que recibieron una dosis de 20 gotas (5 mg) de salbutamol original o similar en solución para nebulizar diluida en 2 ml de solución fisiológica por única vez. Se comparó el volumen espiratorio forzado prebroncodilatador y posbroncodilatador, intragrupos e intergrupos, al inicio y a los 30 minutos. Se determinó el peso de las gotas de salbutamol por gravimetría, la concentración por cromatografía y el número de gotas por envase. Resultados. La respuesta broncodilatadora entre el volumen espiratorio forzado prebroncodilatador y posbroncodilatador fue de 225 ml (IC 95%: 164-286) y 224 ml (IC 95%: 163-284) para salbutamol original y similar, respectivamente (p <0,001). El delta de la diferencia fue de 1,3 ml (IC 95%: -86+83) (p= 0,97). La media, desvío estándar y porcentaje del coeficiente de variación del peso de las gotas fue de 364,75 mg (± 6,01, 1,65) y 543,88 mg (± 56,09, 10,31) (p <0,001) para salbutamol original y similar, respectivamente. Conclusión. No hubo diferencias en la respuesta broncodilatadora medida por el VEF 1 entre salbutamol original y similar. Palabras clave: asma, betaadrenérgicos, medicamentos genéricos, función pulmonar, equivalencia terapéutica. SUMMARY Introduction.According to some clinical evidence original salbutamol should be more effective than a similar one in reverting acute asthma symptoms. Objective. To assess acute pharmacodynamic responses of both drug products in children with asthma, and to establish if bronchodilator response, determined by forced expiratory volume in the first second (FEV 1 ) differs between groups treated with original and similar salbutamol. Design. Prospective, randomized, controlled, double blind study. Patients and methods. One hundred and twenty six children (63 male, age 9.18 ± 2.83 years), were included. They received a single 20 drop (5 mg) dosis of original or similar salbutamol in inhalation solution diluted in 2 ml saline solution. Pre-and post-β 2 FEV 1 were compared intra-and inter-groups, at baseline and after 30 minutes. The weight of salbutamol drops was calculated by gravimetry, the concentration was estimated by chromatography, and number of drops was determined by container. Results. Bronchodilator response between preand post-β 2 FEV 1 was 225 ml (CI 95% 164-286) and 224 ml (CI 95% 163-284) for original and similar salbutamol, respectively (p <0.0001). Difference delta was 1.3 ml (CI 95% -86+83) (p= 0.97). Drop weight (X...

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Pharmacokinetics and Pharmacodynamics of Cumulative Single Doses of Inhaled Salbutamol Enantiomers in Asthmatic Subjects

Cited by 71 publications

References 25 publications

Study Reanalysis Using a Mechanism-Based Pharmacokinetic/Pharmacodynamic Model of Pramlintide in Subjects with Type 1 Diabetes

Study Reanalysis Using a Mechanism-Based Pharmacokinetic/Pharmacodynamic Model of Pramlintide in Subjects with Type 1 Diabetes

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Salbutamol original contra salbutamol similar en niños con crisis de asma. Estudio aleatorizado, controlado y doble ciego

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