Pharmacokinetics of Nadolol, a Beta‐Receptor Antagonist: Administration of Therapeutic Single‐ and Multiple‐Dosage Regimens to Hypertensive Patients

Dreyfuss, Jacques; Griffith, D. L.; Singhvi, Sampat M.; Shaw, James M.; Ross, John; Vukovich, R. A.; Willard, David A.

doi:10.1002/j.1552-4604.1979.tb01641.x

Cited by 46 publications

(25 citation statements)

References 6 publications

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“…45.0 + 3.9 and 40.7 + 3.4 ng/ml. In another recently published study (Dreyfuss et al, 1979) of nadolol concentrations in four hypertensive patients, the average concentration of nadolol found in serum 24 h after the fifth daily dose was 38 ng/ml. Serum concentrations in hypertensive patients at 1, 2, 3 and 4 h after the final dose on Day 13 were 61.9 + 10.0, 85.2 + 22.0, 92.…”

Section: Resultsmentioning

confidence: 89%

“…The pharmacokinetics of nadolol in serum have been described previously (Dreyfuss et al, 1979 Each hypertensive patient received an 80 mg nadolol tablet once a day for 13 days. Samples of venous blood were collected immediately prior to the final dose of nadolol and at hourly intervals for the first 4 h after the final nadolol administration.…”

Section: Introductionmentioning

confidence: 99%

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Nadolol in human serum and breast milk.

Devlin¹,

Duchin²,

Fleiss³

1981

Brit J Clinical Pharma

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1 Simultaneous serum and milk samples were collected over a 10-day period from twelve normotensive, lactating subjects who ingested 80 mg nadolol once daily for a period of 5 days. For comparative purposes, serum samples were also collected from seven patients with a history of mild essential hypertension who ingested the same dose of nadolol for a period of 13 days. 2 In lactating subjects, steady-state serum concentrations of nadolol were attained in 3 days. Milk concentrations of nadolol were much higher than serum concentrations starting on Day 3 and throughout the remainder of the study. The mean (+ s.e. mean) steady-state levels of nadolol in milk (356.9 + 40.4 ng/ml) were 4.6 times higher than the mean steady-state levels in serum (77.3 + 6.9 ng/ml). 3 In hypertensive patients, the mean serum concentration of nadolol 24 h after the twelfth dose was 40.3 + 8.2 ng/ml as compared to a mean serum concentration in lactating subjects of 40.7 3.4 ng/ml, 24 h after the fifth dose. Mean serum concentrations in hypertensive patients at 1 and 4 h after the final daily dose were not significantly different from those in lactating subjects. 4 It can be estimated that a 5 kg nursing infant would consume about 2-7% of the daily adult therapeutic dose of nadolol. The data suggest that caution should be exercised in the use of nadolol in lactating patients.

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Section: Resultsmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Nadolol in human serum and breast milk.

Devlin¹,

Duchin²,

Fleiss³

1981

Brit J Clinical Pharma

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“…The mean predicted concentrations of the quality control (QC) samples deviated by (7.6% from the nominal values for both nadolol (50, 199, and 398 ng/mL) and its stereoisomers (14,50, and 80 ng/mL). Regardless of the analyte, the betweenday and the within-day precision estimates were within 9.5% relative standard deviation.…”

Section: Resultsmentioning

confidence: 92%

“…The literature [30][31][32] indicates that differences in the pharmacokinetics of enantiomeric substrates can occur due to the presence of (i) an active transport in the absorption process, (ii) a preferential first-pass effect or differential substrate specificity for metabolizing enzymes, (iii) varying degree of binding affinities to plasma proteins and tissue components, and/or (iv) preferential biliary and/or renal excretion. In the case of nadolol, the occurrence of either a preferential first pass effect or a differential substrate specificity for metabolism can be ruled out because 14 C studies in humans have demonstrated negligible metabolism of nadolol. 33,34 Furthermore, since the T 1/2 values were not significantly different among the four isomers, a stereoselective renal/biliary excretory process is not likely.…”

Section: Discussionmentioning

confidence: 96%

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Bioequivalence of Two Tablet Formulations of Nadolol Using Single and Multiple Dose Data: Assessment Using Stereospecific and Nonstereospecific Assays

Srinivas

Barr

Shyu

et al. 1996

Journal of Pharmaceutical Sciences

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Nadolol, a nonspecific beta-blocker, is a racemate composed of equal amounts of four stereoisomers, namely, SQ-12148, SQ-12149, SQ-12150, and SQ-12151. In an open-label, randomized, four-period crossover study, the pharmacokinetics of nadolol and its stereoisomers and the bioequivalence of two formulations of nadolol were assessed in 20 healthy male subjects following a single dose (80 mg) and multiple doses (80 mg; once daily for 7 days). A standard granulated tablet and direct compressed tablet formulations, each containing 80 mg of nadolol, with different in vitro dissolution profiles that met current USP requirements were used. The four treatments were single and multiple doses of granulated tablet, and single and multiple doses of compressed tablet. There was a 7 day washout period between successive treatments. All doses of nadolol were administered after an overnight fast. Serial blood samples were collected up to 72 h following the single dose and during multiple dose treatments, following day 6 and 7 doses. Validated high-performance liquid chromatographic assays were applied to measure nadolol and its stereoisomers in the study samples. Plasma concentration data were subjected to noncompartmental pharmacokinetic analysis. Both C(max) and AUC values were significantly greater for SQ-12150 when compared to other nadolol stereoisomers obtained after a single dose or at steady state. However, T(max) and T1/2 values were similar among the four isomers. The observed steady state AUC tau values for nadolol (2278-2331 ng h/ML) or its stereoisomers (550-874 ng h/ML) were significantly greater than those predicted from the single dose AUCinf values (nadolol, 1840-1845 ng h/ML; isomers, 450-713 ng h/ML). The intrasubject variability, computed from multiple dose data, was generally greater for the stereoisomers (17-40%) than for nadolol (10-32%). The two formulations were bioequivalent for nadolol (C(max) = 0.98 [84%, 117%]; AUCinf = 1.03 [93%, 116%]) and SQ-12150 (C(max) = 1.12 [89%, 122%]; AUCinf = 0.98 [82%, 119%]) after a single dose, and only for nadolol (C(max) = 1.07 [84%, 118%]; AUCinf = 1.02 [91%, 113%]) at steady state.

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Preserved Renal Perfusion During Treatment of Essential Hypertension with the Beta Blocker Nadolol

O’Connor

Barg

Duchin

1982

The Journal of Clinical Pharma

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Several beta-adrenergic antagonists impair renal perfusion during treatment of hypertension in man. The acute and chronic effects of a new noncardioselective beta blocker, nadolol, on renal hemodynamics, intravascular volume, and renal electrolyte excretion were studied in 10 men with essential hypertension. Oral nadolol normalized systemic blood pressure without impairment of glomerular filtration rate or renal blood flow, indicating preserved renal blood flow and glomerular filtration rate autoregulation. Intravascular volume and renal excretion of electrolytes were similarly unaltered. Once-daily nadolol lowers blood pressure without renal hemodynamic of functional embarrassment.

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Pharmacokinetics of Nadolol, a Beta‐Receptor Antagonist: Administration of Therapeutic Single‐ and Multiple‐Dosage Regimens to Hypertensive Patients

Cited by 46 publications

References 6 publications

Nadolol in human serum and breast milk.

Nadolol in human serum and breast milk.

Bioequivalence of Two Tablet Formulations of Nadolol Using Single and Multiple Dose Data: Assessment Using Stereospecific and Nonstereospecific Assays

Preserved Renal Perfusion During Treatment of Essential Hypertension with the Beta Blocker Nadolol

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