Factors affecting the pharmacokinetics of nifedipine in humans
Factors affecting the pharmacokinetics of nifedipine in humans
Calcium antagonists are an important class of drugs for the treatment of hypertension, ischaemic heart disease and certain cardiac arrhythmias. Nifedipine is a dihydropyridine calcium antagonist and a substrate of CYP3A enzymes in humans. It undergoes extensive first-pass metabolism after oral administration.
An interaction between nifedipine and grapefruit juice produced a significant increase in the area under the plasma concentration time curve (AUC) of nifedipine after oral but not intravenous dosing compared with control. Grapefruit components inhibit cytochrome P450 medicated oxidation of nifedipine to the nitropyridine metabolite and the site of grapefruit effect is possibly the first-pass metabolism in the intestine.
Flavonoids of grapefruit juice are powerful in vitro inhibitors of CYP3A enzymes and quercetin is a commonly occurring flavonoid. An in vivo study with oral grapefruit juice and quercetin in healthy volunteers showed that unlike grapefruit juice, quercetin did not produce an increase in AUC of nifedipine compared with control. Therefore quercetin is not the cause of grapefruit juice mediated inhibition of nifedipine oxidation and can be excluded as an in vivo inhibitor of CYP3A.
An oral plus intravenous comparison study between South Asians and Caucasians showed a two-fold increase in AUC and t/12 of nifedipine in South Asians who showed a significantly lower-systemic clearance compared to Caucasians but a similar bioavailability. This suggests a lower hepatic CYP3A activity in South Asians compared with Caucasians.
A study of ethnic influence on the kinetics of nifedipine (20 mg oral dose) in 11 healthy Nigerians showed that Nigerians have a more than two-fold increase in AUC and t1/2 compared with Caucasians.
University of Southampton
1994
Rashid, Tahmina Joy
(1994)
Factors affecting the pharmacokinetics of nifedipine in humans.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
Calcium antagonists are an important class of drugs for the treatment of hypertension, ischaemic heart disease and certain cardiac arrhythmias. Nifedipine is a dihydropyridine calcium antagonist and a substrate of CYP3A enzymes in humans. It undergoes extensive first-pass metabolism after oral administration.
An interaction between nifedipine and grapefruit juice produced a significant increase in the area under the plasma concentration time curve (AUC) of nifedipine after oral but not intravenous dosing compared with control. Grapefruit components inhibit cytochrome P450 medicated oxidation of nifedipine to the nitropyridine metabolite and the site of grapefruit effect is possibly the first-pass metabolism in the intestine.
Flavonoids of grapefruit juice are powerful in vitro inhibitors of CYP3A enzymes and quercetin is a commonly occurring flavonoid. An in vivo study with oral grapefruit juice and quercetin in healthy volunteers showed that unlike grapefruit juice, quercetin did not produce an increase in AUC of nifedipine compared with control. Therefore quercetin is not the cause of grapefruit juice mediated inhibition of nifedipine oxidation and can be excluded as an in vivo inhibitor of CYP3A.
An oral plus intravenous comparison study between South Asians and Caucasians showed a two-fold increase in AUC and t/12 of nifedipine in South Asians who showed a significantly lower-systemic clearance compared to Caucasians but a similar bioavailability. This suggests a lower hepatic CYP3A activity in South Asians compared with Caucasians.
A study of ethnic influence on the kinetics of nifedipine (20 mg oral dose) in 11 healthy Nigerians showed that Nigerians have a more than two-fold increase in AUC and t1/2 compared with Caucasians.
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Published date: 1994
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Local EPrints ID: 458508
URI: http://eprints.soton.ac.uk/id/eprint/458508
PURE UUID: 1a6a2679-a635-4bc7-b5c9-02c432510ef5
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Date deposited: 04 Jul 2022 16:50
Last modified: 04 Jul 2022 16:50
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Author:
Tahmina Joy Rashid
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