Simultaneous Determination of Propranolol Enantiomers in Plasma by High-Performance Liquid Chromatography with FIuorescence Detection

Prakash, Chandra; Koshakji, Richard P.; Wood, Alastair J.J.; Blair, Ian A.

doi:10.1002/jps.2600780915

Cited by 27 publications

(13 citation statements)

References 16 publications

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“…The blood samples were transferred immediately to heparinized glass tubes, centrifuged and the plasma transferred to glass tubes and stored at -20°C until analysis for (-)-and (+)-propranolol. The concentrations of (-)-and (+)-propranolol were measured in plasma as described previously (Prakash et al, 1989). The area under the concentration-time curve (AUC), half-life (t½l,) and oral clearance (CL0) were calculated according to standard methods (Gibaldi & Perrier, 1982).…”

Section: Methodsmentioning

confidence: 99%

Lack of effect of ageing on the stereochemical disposition of propranolol.

Whelan

Wood

1992

Brit J Clinical Pharma

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The elderly are more resistant to the effects of propranolol than the young. To determine whether the decreased sensitivity in the elderly could be due to stereoselective alteration in propranolol metabolism, we investigated the effect of age on the oral clearance of (-)-and (+)-propranolol. Six young (aged 24-32, mean 27.3 ± 1.3 years) and six elderly (65-80, mean 71.3 ± 2.7 years) white male volunteers were given a single 80 mg oral dose of racemic propranolol. The mean peak plasma concentrations of both (+)-and (-)-propranolol were significantly higher (P < 0.05) in the elderly (105.7 ± 19.7 and 165.0 ± 29.7 nmol l-1) compared with the young subjects (68.6 ± 10.1 and 115.7 ± 18.1 nmol 1-1). The oral clearances of both (+)-and (-)-propranolol were significantly higher (P < 0.05) in the young (6933 ± 598 and 4554 ± 372 ml min-') than in the elderly (4548 ± 712 and 2941 ± 473 ml min-'). Age had no effect on the relative concentration of the two isomers. Thus, the ratio of (+)-propranolol to (-)-propranolol was 0.67 ± 0.05 in the young compared with 0.65 ± 0.02 in the elderly.

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Section: Methodsmentioning

confidence: 99%

Lack of effect of ageing on the stereochemical disposition of propranolol.

Whelan

Wood

1992

Brit J Clinical Pharma

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“…Similar to the significantly higher plasma clearance for (+)-pirmenol than for (-)-pirmenol, stereoselective clearance was also observed for disopyramide and propranolol in dogs, where clearance of S-(+)-disopyramide and S-(-)-propranolol exceeded their R-enantiomers by 40 to 50% and by two-to threefold, respectively. [9][10][11][12]14 Volume of distribution parameters (V 1 , V ss , V area ) were ∼50% larger for total (+)-pirmenol than for total (-)-pirmenol (S) following the racemate, and 10-49% larger for (+)-pirmenol than for (-)-pirmenol (NS) following individual enantiomer administration. There were no significant differences between enantiomers in elimination half-life and mean residence time whether pirmenol was given as the racemate or the individual enantiomers.…”

Section: Resultsmentioning

confidence: 99%

“…In addition, several investigators have reported stereoselective hepatic metabolism of S-(-)-propranolol in dogs. [11][12][13]15 In this study, possible differences in pharmacokinetics and pharmacodynamics of pirmenol enantiomers were investigated to provide information regarding any potential benefit in the use of either pirmenol enantiomer rather than the racemate. To determine the relative contribution of pirmenol enantiomers to the overall antiarrhythmic effect, (+)-pirmenol, (-)-pirmenol, and pirmenol racemate were each tested in the model of induced ventricular arrhythmia in dogs, which was initially used in the study of pirmenol racemate.…”

Section: Introductionmentioning

confidence: 99%

“…8 Furthermore, both disopyramide and propranolol showed stereoselective pharmacokinetic properties. [9][10][11][12][13] Clearance of S-(+)-disopyramide in dogs was nearly 50% higher than that of R-(-)-disopyramide, with no enantiomer difference in distribution volume. 9, 14 Cook et al 10 also observed stereoselective clearance of disopyramide in dogs, demonstrating a 40% higher renal clearance and greater firstpass metabolism for S-(+)-disopyramide, with N-dealkylation being a stereoselective metabolic pathway.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Pharmacokinetics and Pharmacodynamics of Pirmenol Enantiomers in Coronary Artery Ligated Dogs

Janiczek¹,

Smith²,

Chang³

et al. 1997

Journal of Pharmaceutical Sciences

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The pharmacokinetics and pharmacodynamics of pirmenol enantiomers were investigated in coronary artery ligated mongrel dogs. Reduction in frequency of premature ventricular complexes (PVCs) was determined following intravenous administration of 5-mg/kg doses of racemic pirmenol (n = 5), (+)-pirmenol (n = 4), and (-)-pirmenol (n = 4), each given as a 5-min infusion. Electrocardiographic signals and blood samples were obtained serially over a 4-h period. Pirmenol enantiomer concentrations in plasma were determined by a stereospecific assay. Following the racemate dose, (-)-pirmenol had 47% lower clearance and 33% lower steady-state distribution volume than (+)-pirmenol. These differences could be mostly explained by stereoselective plasma protein binding, reflected in a 58% higher unbound fraction for (+)-pirmenol compared with (-)-pirmenol following racemate administration. Unbound pirmenol distribution volumes were nearly identical for both enantiomers, and unbound clearance was only 16% lower for (-)-pirmenol than (+)-pirmenol following administration of the racemate. Similar trends were observed for pirmenol enantiomers administered individually. Both pirmenol enantiomers were equally effective in arrhythmia suppression. The antiarrhythmic response of coronary artery ligated dogs to pirmenol was described by a sigmoid Emax model, and no statistically significant differences were observed in the pharmacodynamic parameters [i.e., EC50 (plasma concentration at 50% of maximum drug effect), S (constant that reflects the sigmoidal shape of the effect-concentration curve), and EC90 (plasma concentration at 90% of maximum drug effect)] for (+)-pirmenol, (-)-pirmenol, or pirmenol racemate.

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“…Inspired from the sample preparation work in bio analytical area (with focus on extraction, evaporation and reconstitution), different cleaning and decontamination techniques were considered for removing the rHA [9][10][11][12][13][14]. For choosing decontamination technique and development of test preparation method, the following goals were brought into focus:…”

Section: Development Of the Sample Preparationmentioning

confidence: 99%