Effects of Diltiazem on the Pharmacokinetics of Nifedipin

Ohashi, Kyoichi; Tateishi, Tomonori; Sudo, Toshiaki; Sakamoto, Kouichi; Toyosaki, Nobuo; Hosoda, Saichi; Toyo-Oka, Teruhiko; Sugimoto, Kouichi; Kumagai, Yoshito; Ebihara, Akio

doi:10.1097/00005344-199001000-00015

Cited by 19 publications

(14 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Early laboratory investigations provide a theoretic basis for the additive nature of CCB response. These studies suggested a synergistic effect on receptor binding, 22 as well as increased drug concentrations, when diltiazem and a dihydropyridine CCB were concurrently used 23–26 …”

Section: Hypertensionmentioning

confidence: 99%

“…In particular, verapamil and diltiazem inhibit the CYP 3A ‐mediated biotransformation of drugs. A sampling of drugs that undergo CYP‐3A‐mediated biotransformation include simvastatin, 28 lovastatin, 29 cyclosporine, 27 and the aforementioned dihydropyridine CCBs 24–26 . In principle, the interaction between verapamil or diltiazem and a dihydropyridine CCB can be exploited clinically to more effectively treat the hypertensive patient.…”

Section: Dual Calcium Channel Blocker Therapymentioning

confidence: 99%

See 1 more Smart Citation

Combination Calcium Channel Blocker Therapy in the Treatment of Hypertension

Sica¹

2001

J of Clinical Hypertension

View full text Add to dashboard Cite

Effective control of blood pressure is usually achieved only with the use of two or more antihypertensive medications. The treatment options for hypertension are numerous, and the number of possible combinations large. The selection of a specific combination drug regimen has often been linked to the perceived need for diuretic therapy as first- or second-step therapy; thus, the popularity of such drug combinations as an angiotensin-converting enzyme (ACE) inhibitor/diuretic, an angiotensin-receptor blocker/diuretic, or a beta blocker/diuretic. Rational alternatives exist, including an ACE inhibitor/calcium channel blocker (CCB) or a dihydropyridine CCB/b blocker combination. Traditionally, recommendations have advised against the use of combination therapy with two drugs from the same therapeutic class. However, because of the different binding and pharmacologic characteristics of CCBs, a rationale exists for combining different agents in this class in the management of hypertension and/or symptomatic coronary artery disease. In the treatment of either hypertension or angina, combination CCB therapy can prove uniquely successful.

show abstract

Section: Hypertensionmentioning

confidence: 99%

Section: Dual Calcium Channel Blocker Therapymentioning

confidence: 99%

Combination Calcium Channel Blocker Therapy in the Treatment of Hypertension

Sica¹

2001

J of Clinical Hypertension

View full text Add to dashboard Cite

show abstract

“…In cardiovascular treatment, they can lower myocardial oxygen demand by reducing heart rate, blood pressure and myocardial contractility, resulting in decreased angina or improved exercise tolerance [5]. The combined use of nifedipine and diltiazem is believed to be more beneficial than the use of either medication alone for incurable vasospastic angina [5,6]. Herein, we described a case with paralytic ileus induced by the combined use of these two calcium antagonists in the treatment of vasospastic angina.…”

mentioning

confidence: 99%

“…The drug interaction between nifedipine and diltiazem is mediated by hepatic metabolism. Nifedipine is oxidized by the cytochrome P 450 3A4 (CYP 3A4) system in hepatic microsomes, while diltiazem inhibits hepatic microsomal enzyme activity of the CYP 3A4 oxidative process [6]. This diltiazem effect can suppress the hepatic clearance of nifedipine and increase its systemic availability [6].…”

mentioning

confidence: 99%

“…Nifedipine is oxidized by the cytochrome P 450 3A4 (CYP 3A4) system in hepatic microsomes, while diltiazem inhibits hepatic microsomal enzyme activity of the CYP 3A4 oxidative process [6]. This diltiazem effect can suppress the hepatic clearance of nifedipine and increase its systemic availability [6]. Plasma concentrations of nifedipine have been shown to increase about threefold when combined with diltiazem [5].…”

mentioning

confidence: 99%

See 1 more Smart Citation

Paralytic Ileus Induced by the Combined Use of Nifedipine and Diltiazem in the Treatment of Vasospastic Angina

Harada¹,

Ohtaki²,

Sumiyoshi³

et al. 2002

Cardiology

Self Cite

View full text Add to dashboard Cite

The Effect of Diltiazem on Hepatic Drug Oxidation Assessed by Antipyrine and Trimethadione

Ohashi

Sakamoto

Sudo

et al. 1991

The Journal of Clinical Pharma

View full text Add to dashboard Cite

The effect of pretreatment for 3 days with diltiazem 60 mg three times a day on the pharmacokinetics of 500-mg antipyrine and 250-mg trimethadione was studied in six healthy male subjects. Diltiazem decreased the total body clearance from 34.0 +/- 8.0 to 28.6 +/- 6.1 mL/min (P less than .01), and prolonged the elimination half-life from 12.6 +/- 3.0 to 14.3 +/- 2.5 hours (P less than .01) of antipyrine without any changes in volume of distribution. The cumulative renal excretion (% dose) of antipyrine was significantly increased from 2.23 +/- 0.73 to 2.78 +/- 0.83% (P less than .05). Clearances of production for three major antipyrine metabolites, norantipyrine (4.31 +/- 1.64 to 3.50 +/- 1.28 mL/min, P less than .01), 3-hydroxymethylantipyrine (4.67 +/- 1.63 to 3.82 +/- 1.34 mL/min, P less than .01) and 4-hydroxyantipyrine (10.47 +/- 3.41 to 8.16 +/- 2.82 mL/min, P less than .01) were reduced significantly by diltiazem. On the other hand, diltiazem did not produce any significant changes in pharmacokinetic parameters of trimethadione and plasma concentration ratio, oxidative major metabolite of trimethadione to trimethadione itself. These results suggest that other drugs metabolizing the same hepatic oxidative pathways as antipyrine, may be influenced by diltiazem.

show abstract

Effects of Diltiazem on the Pharmacokinetics of Nifedipin

Cited by 19 publications

References 0 publications

Combination Calcium Channel Blocker Therapy in the Treatment of Hypertension

Combination Calcium Channel Blocker Therapy in the Treatment of Hypertension

Paralytic Ileus Induced by the Combined Use of Nifedipine and Diltiazem in the Treatment of Vasospastic Angina

The Effect of Diltiazem on Hepatic Drug Oxidation Assessed by Antipyrine and Trimethadione

Contact Info

Product

Resources

About