The trans‐hepatic extraction of nifedipine.

Challenor, V. F.; Waller, Derek G.; Renwick, A. G.; Gruchy, BS; George, C. F.

doi:10.1111/j.1365-2125.1987.tb03200.x

Cited by 32 publications

(12 citation statements)

References 10 publications

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“…Several studies in animals and man have indicated that gut metabolism may contribute significantly to the overall presystemic elimination of DHPs [24,25,26]. In the case of felodipine, extrahepatic presystemic metabolism in man is indicated by results from a small number of patients with portacaval shunting.…”

Section: Discussionmentioning

confidence: 99%

Relationship between time of intake of grapefruit juice and its effect on pharmacokinetics and pharmacodynamics of felodipine in healthy subjects

Lundahl¹,

Regårdh²,

Edgar³

et al. 1995

Eur J Clin Pharmacol

114

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In this randomised, cross-over study, in nine healthy males given felodipine ER 10 mg PO 200 ml grapefruit juice was found to increase the plasma levels of felodipine even when the juice was taken 24 hours before the drug. Grapefruit juice drunk simultaneously with and 1, 4, 10 or 24 hours before the drug administration resulted in a 32-99% increase in mean Cmax values of felodipine, relative to concomitant water and felodipine intake. The effect on AUC was also significant when juice was taken up to 10 h before the drug. The effect of the interaction decreased with increasing time between juice and drug intake. All treatments produced a significant decrease in diastolic blood pressure and an increase in heart rate in comparison with morning basal values. The change in haemodynamic variables was approximately the same after all treatment combinations. Headache was reported more frequently after treatments including grapefruit juice.

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Section: Discussionmentioning

confidence: 99%

Relationship between time of intake of grapefruit juice and its effect on pharmacokinetics and pharmacodynamics of felodipine in healthy subjects

Lundahl¹,

Regårdh²,

Edgar³

et al. 1995

Eur J Clin Pharmacol

114

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“…Metabolism involves initial oxidation to the nitropyridine analogue by a specific cytochrome P450, CYP3A4 [4], an enzyme present in the liver and small intestine [5]. High plasma concentrations of the nitropyridine metabolite are present after oral, but not intravenous, administration [2], possibly due to metabolism of nifedipine in the intestine [3,5]. Ultimately, the nitropyridine metabolite undergoes cleavage to acid metabolites which are excreted in the urine [6].…”

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confidence: 99%

Factors affecting the absolute bioavailability of nifedipine.

Rashid

Martin

Clarke

et al. 1995

Brit J Clinical Pharma

Self Cite

129

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1. Nifedipine was administered to eight volunteers (seven Caucasian, one East Asian of Chinese origin) as a single 10 mg capsule orally and as 2.5 mg intravenously. The pharmacokinetics were determined under fasting conditions and following 200 ml double strength grapefruit juice taken orally both 2 h before and at the time of dosing. 2. In a separate study, the pharmacokinetics of nifedipine were defined in eight South Asian volunteers (with both parents originating from the Indian subcontinent) following 10 mg nifedipine orally and 2.5 mg intravenously. 3. The administration of grapefruit juice did not alter the pharmacokinetics of intravenous nifedipine, but resulted in a significantly increased area under the plasma concentration‐time curve (AUC) (191 +/‐ 59 c.f. 301 +/‐ 95 ng ml‐1 h, P < 0.05) and bioavailability (0.63 +/‐ 0.18 c.f. 0.86 +/‐ 0.15, P < 0.05) following oral nifedipine. The elimination half‐life was unchanged by administration of grapefruit juice and there was no evidence of decreased formation of the nitropyridine first‐pass metabolite. 4. The AUC of nifedipine after intravenous administration was significantly higher in South Asian subjects than in Caucasians (146 +/‐ 39 c.f. 74 +/‐ 18 ng ml‐1 h, P < 0.002). This was due to a lower systemic clearance in the South Asians which was 50% of that in the Caucasians. The half‐life was markedly prolonged in South Asians (4.1 +/‐ 1.9 c.f. 1.7 +/‐ 0.5 h, P < 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

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“…The differences in pharmacokinetic characteristics between young healthy subjects and congestive heart failure patients did not affect the plasma metabolite profile since the ratio between the AUC of the first pyridine metabolite and the AUC of felodipine was similar in both groups, and no relation was found between cardiac output or changes in cardiac output and this metabolic ratio. (Challenor et al, 1987;Waller et al, 1984). However, such a process cannot entirely explain the differences in felodipine kinetics between the four groups of individuals in Table 3.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of felodipine after intravenous and chronic oral administration in patients with congestive heart failure.

Dunselman

Edgar

Scaf

et al. 1989

Brit J Clinical Pharma

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1 In a randomized, parallel, double-blind study felodipine was administered to 11 and placebo to 12 patients with congestive heart failure. The kinetics of felodipine were studied after acute intravenous administration and after chronic oral treatment for 8 weeks. The relationship between cardiac output and pharmacokinetics was analyzed. The pharmacokinetic data were compared with data from young healthy individuals and hypertensive patients.2 After oral therapy, significant correlations were found between cardiac output and AUC and systemic bioavailability (F). Furthermore, cardiac output before therapy was also significantly correlated with absorption characteristics. No relationship could be demonstrated between cardiac output and i.v. pharmacokinetics. A comparison of patients with heart failure and young healthy individuals revealed that the AUC was three times higher in heart failure patients, while V55 and the ratio of the AUC of the pyridine metabolite to that of felodipine were similar. Oral clearance was reduced by 50% and the terminal half-life was concomitantly increased. Pharmacokinetic data for felodipine are similar in patients with heart failure to published data from elderly hypertensive patients. 3 An increase in liver blood flow during chronic oral therapy, induced by felodipine itself, appears to explain an increase in bioavailability and thus to higher plasma drug concentrations. Thus, it is advisable to start felodipine treatment at a low dosage in patients with congestive heart failure.

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The trans‐hepatic extraction of nifedipine.

Cited by 32 publications

References 10 publications

Relationship between time of intake of grapefruit juice and its effect on pharmacokinetics and pharmacodynamics of felodipine in healthy subjects

Relationship between time of intake of grapefruit juice and its effect on pharmacokinetics and pharmacodynamics of felodipine in healthy subjects

Factors affecting the absolute bioavailability of nifedipine.

Pharmacokinetics of felodipine after intravenous and chronic oral administration in patients with congestive heart failure.

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