Etintidine-propranolol interaction study in humans

Huang, Shiew‐Mei; Weintraub, Howard; Marriott, Thomas B.; Marinan, Barbara; Abels, Robert I.

doi:10.1007/bf01068412

Cited by 7 publications

(3 citation statements)

References 14 publications

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“…This argument can be further verified by comparison of the mean observed clearance (CL) 0.82 L/h/kg (95% CI: 0.64-1.00) [26][27][28]46,47 with mean predicted clearance 0.99 L/h/kg (95% CI: 0.70-1.2) after IV administration. Similarly, CL/F in healthy individuals was also comparable, as its observed and reported values were 217 L/h (95% CI: 183.6-250.80) 26,[29][30][31][32][33]46,[48][49][50][51][52] and 183.3 L/h (95% CI: 169.9-196.6), respectively. Furthermore, the AFE value for CL (0.83 and 1.15 after IV and oral dose predictions) strengthened the argument that the developed PBPK model was predicting the disposition of the drug precisely (Table 4).…”

Section: Discussionsupporting

confidence: 73%

“…Data from 22 clinical studies (7 for IV administration and 15 for oral administration) in healthy individuals was extracted. One-third (3 IV 26-28 and 5 oral [29][30][31][32][33] ) of which were used for the development of the PBPK model and the rest of the two-thirds (4 IV and 10 oral) were used for subsequent model verifications. All the observed data sets were used for model evaluation.…”

Section: Materials and Methodology Clinical Pharmacokinetic Datamentioning

confidence: 99%

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Development and Evaluation of a Physiologically Based Pharmacokinetic Drug-Disease Model of Propranolol for Suggesting Model Informed Dosing in Liver Cirrhosis Patients

Kalam¹,

Rasool²,

Alqahtani³

et al. 2021

DDDT

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The study was aimed to understand the underlying causes for the differences in propranolol pharmacokinetics (PK) between healthy and cirrhosis populations by using a systematic whole-body physiologically based pharmacokinetic (PBPK) model-building approach for suggesting model informed propranolol dosing in liver cirrhosis patients with different stages of disease severity. Methods: A whole-body PBPK model was developed by using population simulator PK-Sim ® by using reported physicochemical and clinical data for propranolol in healthy and liver cirrhosis populations. The model evaluation was done by visual verification and comparison of PK parameters using their observed/predicted ratios (R obs/pred). Results: The developed model has effectively described the disposition of propranolol after intravenous and oral application in healthy and liver cirrhosis populations. All the model predictions were comparable to the observed clinical data and the R obs/pred for all the PK parameters were within a 2-fold range. A significant increase in plasma concentration of propranolol and decrease in drug clearance was observed in progressive stages of liver cirrhosis. The developed model after evaluation with the reported clinical PK data was used for suggesting model informed propranolol dosing in different stages of liver cirrhosis based on systemic unbound drug concentration. Conclusion: The developed PBPK model has successfully described propranolol PK in healthy and cirrhosis populations after IV and oral administration. The evaluated PBPK propranolol-cirrhosis model can have many implications in predicting propranolol dosing in liver cirrhosis patients with different stages of disease severity.

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Section: Discussionsupporting

confidence: 73%

Section: Materials and Methodology Clinical Pharmacokinetic Datamentioning

confidence: 99%

Development and Evaluation of a Physiologically Based Pharmacokinetic Drug-Disease Model of Propranolol for Suggesting Model Informed Dosing in Liver Cirrhosis Patients

Kalam¹,

Rasool²,

Alqahtani³

et al. 2021

DDDT

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“…Cimetidine [120,175,1 78,189,191 ,192,221 ,238) and etintidine [205] are the only H2-receptor antagonists known to cause a decrease in clearance of theophylline (12 to 44% and 65%, respectively). Consequently, these agents both prolong the tY2 of theophylline (by 11 to 80% for cimetidine).…”

Section: Enzyme Inhibitionmentioning

confidence: 99%

Influence of Endogenous and Exogenous Effectors on the Pharmacokinetics of Theophylline

Tröger

Meyer

1995

Clinical Pharmacokinetics

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Theophylline has been widely used as a bronchodilatory drug for the treatment of neonatal apnoea in premature newborns and patients with obstructive airways disease. The development of analytical equipment and procedures to determine the systemic concentration of theophylline renders it possible to improve the effectiveness of theophylline therapy and reduce the incidence of toxic and adverse effects. Since the beginning of the 1970s, endogenous and exogenous factors (e.g. age, blood pH, concomitant diseases and drug therapy, meal preparation procedure, nutritional habits, pregnancy, gender, smoking and, to a lesser extent, biorhythms), influencing nearly all parameters of theophylline pharmacokinetics have been described. Drug absorption depends on galenic formulation, drug delivery, nutritional habits and the chemical derivatives used. The mean plasma protein binding rates depend on the method of plasma protein determination: acidic blood pH values and advanced age may result in reduced plasma proteins. The volume of distribution depends primarily on age; it is 2-fold greater in newborns than in adults. Furthermore, changes in blood pH values, the plasma protein content and the administration of concomitant drugs may vary this parameter. Biotransformation is the most clinically important pharmacokinetic parameter. Hepatic metabolism accounts for 90% of the metabolism of theophylline. Essentially, 2 microsomal isoenzymes of the cytochrome P450 system appear to be responsible for the N-methylation and 8-hydroxylation of the drug. Age and concomitant disease are the major endogenous effectors influencing biotransformation of theophylline, whereas biorhythms, gender and pregnancy are of lesser importance. Exogenous factors, such as concomitantly administered drugs, smoking and nutritional factors, affect biotransformation by inducing or inhibiting the metabolising enzymes. Because of intra- and interindividual variability in the pharmacokinetics of theophylline, which may be increased by the presence of endogenous and/or exogenous effectors, it is necessary to supervise theophylline therapy by therapeutic drug monitoring if target concentrations are to be achieved.

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Two reproducible and sensitive liquid chromatographic methods to quantify atenolol and propranolol in human plasma and determination of their associated analytical error functions

Braza

Modamio

Hernández

2000

Journal of Chromatography B: Biomedical Sciences and Applicatio

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Etintidine-propranolol interaction study in humans

Cited by 7 publications

References 14 publications

Development and Evaluation of a Physiologically Based Pharmacokinetic Drug-Disease Model of Propranolol for Suggesting Model Informed Dosing in Liver Cirrhosis Patients

Development and Evaluation of a Physiologically Based Pharmacokinetic Drug-Disease Model of Propranolol for Suggesting Model Informed Dosing in Liver Cirrhosis Patients

Influence of Endogenous and Exogenous Effectors on the Pharmacokinetics of Theophylline

Two reproducible and sensitive liquid chromatographic methods to quantify atenolol and propranolol in human plasma and determination of their associated analytical error functions

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