Ethnic differences in the pharmacokinetics of oral nifedipine.

Ahsan, C. H.; Renwick, A. G.; Macklin, B. S.; Challenor, V. F.; Waller, Derek G.; George, C. F.

doi:10.1111/j.1365-2125.1991.tb05552.x

Cited by 61 publications

(35 citation statements)

References 17 publications

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“…We have previously shown that South Asian subjects had much higher concentrations of nifedipine in the plasma than Caucasians, following oral doses of 10 and 20 mg capsules of nifedipine [21,22]. The mean AUC in the South Asians was over twice that of the Caucasians and was considered to be due to a combination of lower first-pass metabolism and reduced systemic clearance of nifedipine in this group.…”

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confidence: 85%

Factors affecting the absolute bioavailability of nifedipine.

Rashid

Martin

Clarke

et al. 1995

Brit J Clinical Pharma

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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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confidence: 85%

Factors affecting the absolute bioavailability of nifedipine.

Rashid

Martin

Clarke

et al. 1995

Brit J Clinical Pharma

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129

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“…In addition to genetic factors, it is likely that interethnic differences in diet composition contribute to these differences. For example, one could speculate that a higher pepper intake in South Asians compared with Caucasians contributed to 3-fold higher plasma concentrations of the CYP3A4 substrate nifedipine, which was observed in the former group (Ahsan et al, 1991).…”

Section: Discussionmentioning

confidence: 99%

Piperine, a Major Constituent of Black Pepper, Inhibits Human P-glycoprotein and CYP3A4

Bhardwaj

Glaeser²,

Becquemont³

et al. 2002

J Pharmacol Exp Ther

452

297

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Dietary constituents (e.g., in grapefruit juice; NaCl) and phytochemicals (e.g., St. John's wort) are important agents modifying drug metabolism and transport and thereby contribute to interindividual variability in drug disposition. Most of these drug-food interactions are due to induction or inhibition of P-glycoprotein and/or CYP3A4. Preliminary data indicate that piperine, a major component of black pepper, inhibits drugmetabolizing enzymes in rodents and increases plasma concentrations of several drugs, including P-glycoprotein substrates (phenytoin and rifampin) in humans. However, there are no direct data whether piperine is an inhibitor of human Pglycoprotein and/or CYP3A4. We therefore investigated the influence of piperine on P-glycoprotein-mediated, polarized transport of digoxin and cyclosporine in monolayers of Caco-2 cells. Moreover, by using human liver microsomes we determined the effect of piperine on CYP3A4-mediated formation of the verapamil metabolites D-617 and norverapamil. Piperine inhibited digoxin and cyclosporine A transport in Caco-2 cells with IC 50 values of 15.5 and 74.1 M, respectively. CYP3A4-catalyzed formation of D-617 and norverapamil was inhibited in a mixed fashion, with K i values of 36 Ϯ 8 (liver 1)/49 Ϯ 6 (liver 2) and 44 Ϯ 10 (liver 1)/77 Ϯ 10 M (liver 2), respectively. In summary, we showed that piperine inhibits both the drug transporter P-glycoprotein and the major drug-metabolizing enzyme CYP3A4. Because both proteins are expressed in enterocytes and hepatocytes and contribute to a major extent to first-pass elimination of many drugs, our data indicate that dietary piperine could affect plasma concentrations of P-glycoprotein and CYP3A4 substrates in humans, in particular if these drugs are administered orally.Several dietary constituents and phytochemicals are now identified as important factors affecting drug disposition

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“…Some previous investigators postulated that populations may be characterised as either fast or slow absorbers of nifedipine [4,6]. Similarly, while some showed high bioavailability and there were others who showed low availability [10].…”

Section: Ethnic Differences and Other Nifedipine Pharmacokineticsmentioning

confidence: 99%

“…[1] There are numerous publications on the bioavailability and pharmacokinetics of nifedipine [1][2][3] but no work on the pharmacokinetics of nifedipine in the Pakistani population has been reported previously, to the best of our knowledge. Such a study would be important since it should provide useful information on drug blood levels and metabolic status [4][5][6][7] which could influence the use of this drug among Pakistanis. Furthermore, some dosage adjustments may be needed, based on pharmacokinetic data, for patients in this region of the world [8][9][10].…”

Section: Introductionmentioning

confidence: 99%