Comparative beta‐adrenoceptor blocking effects and pharmacokinetics of penbutolol and propranolol in man.

Jf, Giudicelli; Richer, Christine; Chauvin, M.; Idrissi, N; Berdeaux, Alain

doi:10.1111/j.1365-2125.1977.tb00684.x

Cited by 35 publications

(4 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Corresponding values for the (+ )-isomers were 120, 8 and >4. Overall, these results are consistent with data from the literature which describe (±)-pindolol as being 3-40 times more potent (Giudicelli et al, 1969;Hill & Turner, 1969;Aellig, 1976), (-)-penbutolol 4-26 times more potent (Boissier et al, 1973;Giudicelli et al, 1977;Sharma & Sapru, 1978) and (±)-metoprolol 2-4 times less potent (Ablad et al, 1973;Boucher & Duchene-Marullaz, 1980) than (± )propranolol.…”

Section: Discussionsupporting

confidence: 90%

Studies on the stereoisomers of β‐adrenoceptor antagonists in conscious A‐V blocked dogs

Boucher

Duchêne-Marullaz

Moundanga

1986

British J Pharmacology

View full text Add to dashboard Cite

1 Atrial and ventricular chronotropic effects of the individual stereoisomers of propranolol, pindolol, metoprolol and penbutolol were studied in conscious dogs with chronic atrio-ventricular (A-V) block. Ventricular P-adrenoceptor blocking activity was assessed for all drugs against isoprenaline under the same experimental conditions. 2 At low doses, the stereoisomers ofpropranolol and penbutolol decreased atrial rate, whereas those of pindolol and metoprolol produced an increase. At higher doses, all drugs increased atrial rate. All drugs decreased ventricular rate dose-dependently except (+ )-pindolol.3 Relative ventricular P-blocking potencies of the (-)-isomers of propranolol, pindolol, metoprolol and penbutolol were respectively 38, 21, >43 and 31 times higher than those of their corresponding (+ )-isomers. In addition, P-blocking potencies of (-)-and (+ )-pindolol were respectively 60 and 120 times higher, those of (-)-and (+ )-penbutolol 7 and 8 times higher and those of (-)-and (+)-metoprolol 4 and >4 times weaker than those of (-)-and (+ )-propranolol. 4 At comparable levels of ventricular P-adrenoceptor blockade, (-)-pindolol and (-)-metoprolol were more potent in producing ventricular bradycardia than their respective (+)-isomers, whereas (-)-and (+ )-propranolol and (-)-and (+ )-penbutolol were equiactive. In addition, regardless of which isomer was being studied, the order of ventricular bradycardiac potencies, at comparable levels of P-adrenoceptor blockade, was metoprolol > propranolol > penbutolol > pindolol. 5 These results show that antagonism of P-adrenoceptors in the ventricle is at least partly responsible for the ventricular bradycardiac effect produced by these drugs, but also that some other factor, apparently distinct from the membrane stabilizing activity, is involved, suggesting the existence of some other as yet unknown pharmacological property of the P-adrenoceptor blocking drugs, especially evident in metoprolol. Finally, these results demonstrate that the intrinsic sympathomimetic activity exhibited by some of these drugs attenuate their bradycardiac effect.

show abstract

Section: Discussionsupporting

confidence: 90%

Studies on the stereoisomers of β‐adrenoceptor antagonists in conscious A‐V blocked dogs

Boucher

Duchêne-Marullaz

Moundanga

1986

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…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%

See 1 more Smart Citation

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

View full text Add to dashboard Cite

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.

show abstract

Measurement of penbutolol and 4‐hydroxypenbutolol in plasma or serum by HPLC

Bhamra

Flanagan

Holt

1986

Biomedical Chromatography

View full text Add to dashboard Cite

A simple HPLC method for penbutolol and 4-hydroxypenbutolol assay has been developed. Plasma or serum (200 microliters) is vortex-mixed (30 s) with Tris solution (2 M, pH 10.6) containing an internal standard (50 microliters) and methyl t-butyl ether (200 microliters). After centrifugation, the extract (100 microliters) is analysed using an unmodified silica column (250 x 5 mm ID) and iso-octane-methanol-methyl t-butyl ether (55:25:20) containing ammonium perchlorate (10 mM, pH 5.7) as eluent and with fluorescence detection. No interference has been encountered and the limit of accurate measurement for both compounds is 5 micrograms/l.

show abstract

Comparative beta‐adrenoceptor blocking effects and pharmacokinetics of penbutolol and propranolol in man.

Cited by 35 publications

References 10 publications

Studies on the stereoisomers of β‐adrenoceptor antagonists in conscious A‐V blocked dogs

Studies on the stereoisomers of β‐adrenoceptor antagonists in conscious A‐V blocked dogs

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

Measurement of penbutolol and 4‐hydroxypenbutolol in plasma or serum by HPLC

Contact Info

Product

Resources

About