A study of the pharmacokinetics and pharmacodynamics of nifedipine in combination with atenolol

Fitzsimons, TJ; Norris, S. C.; Adam, H. K.; Ryan, Jerome R.; McAinsh, J

doi:10.1002/bdd.2510120109

Cited by 6 publications

(1 citation statement)

References 4 publications

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“…Similarly for AT the maximum concentration in plasma ( C max 393 ± 102 ng/mL) were attained at 3.80 ± 1.48 h, and the AUC 0–∞ and t 1/2 were found to be 3781 ± 951 ng h/mL and 8.15 ± 2.51 h, respectively. The pharmacokinetics parameters obtained in this study were in close agreement with earlier reported values for NF and AT in combination (Fitzsimons et al ., ).…”

Section: Resultsmentioning

confidence: 97%

Sensitive LC‐MS/MS‐ESI method for simultaneous determination of nifedipine and atenolol in human plasma and its application to a human pharmacokinetic study

Kallem

Inamadugu²,

Mullangi

et al. 2012

Biomedical Chromatography

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A rapid, simple, sensitive and selective LC-MS/MS method has been developed and validated for quantification of nifedipine (NF) and atenolol (AT) in human plasma (250 μL). The analytical procedure involves a one-step liquid-liquid extraction method using carbamazepine as an internal standard (IS). The chromatographic resolution was achieved on a Hypurity Advance C(18) column using an isocratic mobile phase consisting of 5 mm ammonium acetate-acetonitrile (15:85, v/v) at flow rate of 1.0 mL/min. The LC-MS/MS was operated under the multiple-reaction monitoring mode using electrospray ionization. The total run time of analysis was 2 min and elution of NF, AT and IS occurred at 0.79, 1.04 and 0.76 min, respectively. A detailed method validation was performed as per the FDA guidelines and the standard curves found to be linear in the range of 1.02-101 ng/mL for NF and 5.05-503 ng/mL for AT, with a coefficient of correlation of ≥ 0.99 for both the drugs. NF and AT were found to be stable in a battery of stability studies, viz. bench-top, auto-sampler and repeated freeze-thaw cycles. The validated assay method was successfully applied to a pharmacokinetic study in humans.

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Section: Resultsmentioning

confidence: 97%

Sensitive LC‐MS/MS‐ESI method for simultaneous determination of nifedipine and atenolol in human plasma and its application to a human pharmacokinetic study

Kallem

Inamadugu²,

Mullangi

et al. 2012

Biomedical Chromatography

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Enantioselective inhibitory effect of nicardipine on the hepatic clearance of propranolol in man

et al. 1994

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The influence of a single oral dose of 30 mg nicardipine on the pharmacokinetics of (R)- and (S)-propranolol, given orally as rac-propranolol 80 mg, was studied in 12 healthy volunteers. The plasma concentrations were higher for the (S)-enantiomer than for the (R)-enantiomer. The Cl(o) and the Cl'intr of (S)-propranolol were significantly lower than the Cl(o) and Cl'intr of (R)-propranolol. The unbound fraction of (R)-propranolol was significantly higher than that of (S)-propranolol. Coadministration of nicardipine significantly increased the AUC and Cmax and significantly decreased the Cl(o) and Cl'intr for unbound drug of (R)- and (S)-propranolol. These changes were more important for (R)- than for (S)-propranolol. The protein binding was not altered by nicardipine. The enantioselective effect of nicardipine on the metabolic clearance of propranolol appears to be due to an interaction at the level of the metabolizing enzymes. The effect on blood pressure of rac-propranolol was little affected when nicardipine was coadministered with rac-propranolol, and its bradycardic effect was reduced.

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A Pharmacokinetic and Pharmacodynamic Study of the Potential Drug Interaction between Tasosartan and Atenolol in Patients with Stage 1 and 2 Essential Hypertension

Andrawis

Battle

Klamerus

et al. 2000

The Journal of Clinical Pharma

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The primary objective of this study was to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of tasosartan and atenolol administered alone and concomitantly under steady-state conditions in 17 patients ages 18 to 65 years diagnosed with stage 1 to 2 essential hypertension. After a 3- to 14-day qualification period, all patients received placebo tasosartan on days--1 through 5 and 25 through 34, atenolol alone (50 mg) on days 1 through 5, atenolol (50 mg) + tasosartan (50 mg) on days 6 through 19, and tasosartan (50 mg) alone on days 20 through 24. A PK and PD evaluation of atenolol alone was performed on study day 5. On study day 19, PK and PD of both tasosartan and atenolol were assessed. PK and PD evaluation for tasosartan alone was assessed on study day 24. The coadministration of atenolol + tasosartan did not affect the pharmacokinetics of tasosartan, its major metabolite (enoltasosartan), or atenolol when compared with tasosartan or atenolol administered separately. For area under the change in diastolic blood pressure curve, the reduction was significantly greater after tasosartan + atenolol compared with that after atenolol alone (336 +/- 85 and 190 +/- 71 mmHg.24 h; p < 0.05 for combination and atenolol alone, respectively; mean +/- SEM). Combination therapy also caused a maximal reduction in diastolic blood pressure that is significantly more than with monotherapy with atenolol (-27 +/- 2 mmHg and -20 +/- 2 mmHg, respectively, p < 0.05). The additive effects of tasosartan and atenolol in decreasing diastolic blood pressure may provide a rationale for combination antihypertensive therapy.

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A study of the pharmacokinetics and pharmacodynamics of nifedipine in combination with atenolol

Cited by 6 publications

References 4 publications

Sensitive LC‐MS/MS‐ESI method for simultaneous determination of nifedipine and atenolol in human plasma and its application to a human pharmacokinetic study

Sensitive LC‐MS/MS‐ESI method for simultaneous determination of nifedipine and atenolol in human plasma and its application to a human pharmacokinetic study

Enantioselective inhibitory effect of nicardipine on the hepatic clearance of propranolol in man

A Pharmacokinetic and Pharmacodynamic Study of the Potential Drug Interaction between Tasosartan and Atenolol in Patients with Stage 1 and 2 Essential Hypertension

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