Stereoselective pharmacokinetics of oral and intravenous nitrendipine in healthy subjects

Soons, P. A.; Roosemalen, M.C.M.; Breimer, D.D.

doi:10.1016/0014-2999(90)93832-b

Cited by 5 publications

(3 citation statements)

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“…This was expected because the systemic elimination of high-clearance drugs as racemic nitrendipine and its enantiomers is limited by liver blood flow rather than metabolic enzyme activity. 3,9 The t max of both enantiomers was not different both within and between cotreatments. No effects on t ma x were observed in other cimetidine-dihydropyridine interaction studies.…”

Section: Discussionmentioning

confidence: 83%

Grapefruit juice and cimetidine inhibit stereoselective metabolism of nitrendipine in humans

Soons

Vogels

Roosemalen

et al. 1991

Clin Pharmacol Ther

109

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The effects of grapefruit juice (150 ml at -15, -10, -1/4, +5, and +10 hours) and cimetidine (200 mg at the same times) on the stereoselective pharmacokinetics and effects of 20 mg oral racemic nitrendipine were investigated in a placebo-controlled crossover study in nine healthy men. In all subjects the AUC of racemic nitrendipine was increased by grapefruit juice (mean increase 106%; 95% confidence interval 64% to 158%) and cimetidine treatment (+154%; 95% confidence interval 77% to 265%). Comparable results were obtained for the peak plasma drug concentration and for both parameters of (S)- and (R)-nitrendipine. There were highly significant differences in the area under the concentration-time curve and peak plasma drug concentration between enantiomers within all treatments. Grapefruit juice had no effect on this stereoselectivity, but cimetidine increased the mean S/R ratio of areas under the curve (2.25) by 20% (95% confidence interval 12% to 29%) compared with placebo treatment (1.89). Half-lives and time to reach peak concentration of the enantiomers were not different within and between treatments. There were no consistent effects on blood pressure with all treatments, but in most subjects there was a small temporary increase in heart rate after intake of nitrendipine. Grapefruit juice and cimetidine did not affect these hemodynamic parameters and did not cause additional adverse effects.

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Section: Discussionmentioning

confidence: 83%

Grapefruit juice and cimetidine inhibit stereoselective metabolism of nitrendipine in humans

Soons

Vogels

Roosemalen

et al. 1991

Clin Pharmacol Ther

109

View full text Add to dashboard Cite

show abstract

“…The collected fractions that contained the desired enantiomers required an additional extraction into an organic solvent suitable for injection into the GC/MS system. Another successful application of CSP-HPLC combined with GC-electron capture detection to 1,Cdihydropyridine drugs was reported by Soons et al 9 A variety of racemic drugs could be separated and the method applied to serum samples.…”

mentioning

confidence: 99%

Simultaneous Assessment of the Intravenous and Oral Disposition of the Enantiomers of Racemic Nimodipine by Chiral Stationary- Phase High-Performance Liquid Chromatography and Gas Chromatography/Mass Spectroscopy Combined with a Stable Isotope Technique

Fischer

Schönberger

Mück

et al. 1993

Journal of Pharmaceutical Sciences

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“…Previous studies have shown that the S‐enantiomer of nitrendipine is 7–8 times more potent than the R‐enantiomer [9]. In addition, the bioavailability of the S‐enantiomer is greater than that of the R‐enantiomer [10, 11]. Therefore, the measurement of plasma concentrations of these enantiomers separately may be relevant to our understanding of the clinical importance of the present drug interaction.…”

Section: Discussionmentioning

confidence: 99%

Effect of bile acids on absorption of nitrendipine in healthy subjects

Sato

Maeda

Sakamoto

et al. 2001

Brit J Clinical Pharma

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Aims To examine whether bile acids such as ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) can in¯uence the absorption of nitrendipine, a highly lipophilic calcium channel blocker. Methods Six healthy subjects received nitrendipine (10 mg) with and without UDCA (50 mg) and CDCA (200 and 600 mg) with an interval of 1y2 weeks between study phases. Results Bile acids decreased the C max (ng ml x1 ) [control 10.9t5.8 (meants.d.), UDCA 5.0t4.7 (95% con®dence interval for difference; 3.9, 7.8, P=0.0006), CDCA (600 mg) 5.0t3.9 (2.6, 9.2, P=0.0059)] and AUC (ng ml x1 h) [(control; 60t36, UDCA 15t13 (20, 73, P=0.0064), CDCA (600 mg) 19t19 (21, 63, P=0.0038)] of nitrendipine, while elimination half-life remained unchanged. Conclusions These results suggest that the amount of nitrendipine absorbed was decreased when the drug was administered with UDCA and CDCA.

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Stereoselective pharmacokinetics of oral and intravenous nitrendipine in healthy subjects

Cited by 5 publications

References 0 publications

Grapefruit juice and cimetidine inhibit stereoselective metabolism of nitrendipine in humans

Grapefruit juice and cimetidine inhibit stereoselective metabolism of nitrendipine in humans

Simultaneous Assessment of the Intravenous and Oral Disposition of the Enantiomers of Racemic Nimodipine by Chiral Stationary- Phase High-Performance Liquid Chromatography and Gas Chromatography/Mass Spectroscopy Combined with a Stable Isotope Technique

Effect of bile acids on absorption of nitrendipine in healthy subjects

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