A case of variant angina exacerbated by administration of rifampicin

Tsuchihashi, Kazufumi; Fukami, Kenichi; Kishimoto, Hiroshi; Sumiyoshi, Tetsuya; Haze, Kazuo; Saito, Muneyasu; Hiramori, Katsuhiko

doi:10.1007/bf02058314

Cited by 12 publications

(7 citation statements)

References 16 publications

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“…Decreased drug concentrations of several calcium‐channel antagonists followed by rifampin treatments reduce their therapeutic effects . The effect of rifampin on the blood pressure‐lowering effect of benidipine was not significant in the present study, although plasma concentrations were significantly reduced.…”

Section: Discussioncontrasting

confidence: 70%

Effect of rifampin on enantioselective disposition and anti‐hypertensive effect of benidipine

Sunwoo

Nguyen

Chien

et al. 2019

Brit J Clinical Pharma

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AIMSIn vitro study showed that benidipine is exclusively metabolized by cytochrome P450 (CYP) 3A. This study evaluated the effect of rifampin on the enantioselective disposition and anti-hypertensive effect of benidipine. METHODSBenidipine (8 mg) was administered to healthy subjects with or without repeated rifampin dosing, in a crossover design. Plasma concentrations of (S)-(S)-(+)-α and (R)-(R)-(À)-α isomers of benidipine and blood pressure were measured for up to 24 h after dosing. In addition, CYP3A metabolic capacity was evaluated in each subject using oral clearance of midazolam. RESULTSThe exposure of (S)-(S)-(+)-α-benidipine was greater than that of (R)-(R)-(À)-α-benidipine by approximately three-fold following single dose of benidipine. Repeated doses of rifampin significantly decreased the exposure of both isomers. Geometric mean ratios (GMRs) (95% CI) of C max and AUC ∞ for (S)-(S)-(+)-α-benidipine were 0.14 (0.10-0.18) and 0.12 (0.08-0.18), respectively. GMRs (95% CI) of C max and AUC ∞ for (R)-(R)-(À)-α-benidipine were 0.10 (0.06-0.17) and 0.10 (0.06-0.17), respectively. Oral clearances of both isomers were increased equally by approximately 10-fold. There were no significant differences in cardiovascular effect following benidipine administration between control and rifampin treatment. CYP3A activity using midazolam did not appear to correlate with oral clearance of benidipine. CONCLUSIONSAfter single administration of racemic benidipine, enantioselective disposition of (S)-(S)-(+)-αand (R)-(R)-(À)-α-benidipine was observed. Treatments with rifampin significantly decreased the exposure of both isomers but appeared to marginally affect its blood pressure-lowering effect in healthy subjects. Impact of coadministration of rifampin on the treatment effects of benidipine should be assessed in hypertensive patients. British Journal of Clinical PharmacologyBr J Clin Pharmacol (2019) 85 737-745 737• Benidipine is a racemic mixture of two isomers ((R)-(R)-(À)-α and (S)-(S)-(+)-α).• Our previous study indicated that benidipine was metabolized by CYP3A4 and CYP3A5.• Rifampin is a potent inducer of CYP3A4 that can decrease the antihypertensive effects of calcium channel blockers. WHAT THIS STUDY ADDS• A clinical study in healthy subjects was conducted to evaluate the enantioselective disposition of benidipine.• This study describes for the first time the effect of rifampin on the pharmacokinetic and pharmacodynamic properties of benidipine and its enantiomers to establish the mechanism of the drug interaction. Study design flow chart Effect of rifampin on benidipine PK/PD Br J Clin Pharmacol (2019) 85 737-745 739 Effect of rifampin on benidipine PK/PD Br J Clin Pharmacol (2019) 85 737-745 745

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Section: Discussioncontrasting

confidence: 70%

Effect of rifampin on enantioselective disposition and anti‐hypertensive effect of benidipine

Sunwoo

Nguyen

Chien

et al. 2019

Brit J Clinical Pharma

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“…Therefore, patients receiving theophylline preparations should be observed carefully for reductions in theophylline plasma concentrations when rifampin is given. Similarly, increased metabolism of orally administered calcium channel blockers has been observed in patients given rifampin (27,28). This effect may be explained by an enhanced first-pass metabolism caused by rifampin.…”

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confidence: 87%

Rifampin Use in Peritoneal Dialysis

Zimmerman

Johnson

1989

Perit Dial Int

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“…Pharmacokinetic studies in healthy volunteers and case studies of hypertensive patients have described significant interactions of beta-blockers (BB) and calcium-channel blockers (CCB) with rifampicin. [ 9 10 11 12 13 ] However, the interaction could be unpredictable in the presence of renal dysfunction due to factors such as decreased renal excretion of anti-HTs, decreased serum rifampicin levels, the tendency for fluid retention, renin-mediated hypertension and clearance of drugs during dialysis.…”

Section: Introductionmentioning

confidence: 99%

Rifampicin and anti-hypertensive drugs in chronic kidney disease: Pharmacokinetic interactions and their clinical impact

et al. 2016

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Patients on dialysis have an increased incidence of tuberculosis (TB). Rifampicin, a first-line antitubercular therapy (ATT) drug, is a potent inducer of hepatic cytochrome P450 (CYP). There is potential for pharmacokinetic interaction between rifampicin and anti-hypertensives that are CYP substrates: amlodipine and metoprolol. Therefore, hypertensive patients receiving rifampicin-based ATT are at risk for worsening of hypertension. However, this hypothesis has not yet been systematically studied. In this prospective study, hypertensive CKD 5D patients with TB were followed after rifampicin initiation. Blood pressure (BP) was ≤140/90 mmHg with stable anti-HT requirement at inclusion. Serum amlodipine, metoprolol, and prazosin levels were estimated by high-performance liquid chromatography at baseline and 3, 7, 10, and 14 days after rifampicin initiation. BP and anti-HT requirement were monitored for 2 weeks or until stabilization. All 24 patients in the study had worsening of hypertension after rifampicin and 83.3% required increase in drugs to maintain BP <140/90 mmHg. Serial amlodipine levels were estimated in 16 patients; metoprolol and prazosin in four patients each. Drug levels declined by >50% in all patients and became undetectable in 50-75%. Drug requirement increased from 4.5 ± 3.6 to 8.5 ± 6.4 units (P < 0.0001). Mean time to first increase in dose was 6.5 ± 3.6 days. Eleven (46%) patients experienced a hypertensive crisis at 9.1 ± 3.8 days. Three of them had a hypertensive emergency with acute pulmonary edema. In two patients, rifampicin had to be discontinued to achieve BP control. In conclusion, rifampicin caused a significant decrease in blood levels of commonly used anti hypertensives. This decrease in levels correlated well with worsening of hypertension. Thus, we suggest very close BP monitoring in CKD patients after rifampicin initiation.

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A case of variant angina exacerbated by administration of rifampicin

Cited by 12 publications

References 16 publications

Effect of rifampin on enantioselective disposition and anti‐hypertensive effect of benidipine

Effect of rifampin on enantioselective disposition and anti‐hypertensive effect of benidipine

Rifampin Use in Peritoneal Dialysis

Rifampicin and anti-hypertensive drugs in chronic kidney disease: Pharmacokinetic interactions and their clinical impact

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