Variability in nifedipine pharmacokinetics and dynamics: A new oxidation polymorphism in man

Kleinbloesem, C. H.; Brummelen, P. Van; Faber, Hette; Danhof, Meindert; Vermeulen, Nico; Breimer, D. D.

doi:10.1016/0006-2952(84)90165-5

Cited by 173 publications

(69 citation statements)

References 4 publications

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“…Kleinbloesem et al (1984) reported a bimodal distribution in the AUC of nifedipine following 20. mg administered as capsules, which was not found by other workers following administration of 20 mg as tablets (Schellens et al, 1988) or 10 mg as capsules (Renwick et al, 1988). The precise posture adopted by subjects in the study by Kleinbloesem et al (1984) was not reported and it is possible that failure to control for posture may have contributed to the bimodality detected. Posture-dependent saturation of presystemic extraction and/or metabolism would be more likely with 20 mg nifedipine as capsules than with the tablet formation or following 10 mg as capsules, and this may explain the discrepancies between these earlier studies.…”

Section: Discussionmentioning

confidence: 99%

The influence of posture on the pharmacokinetics of orally administered nifedipine.

Renwick

Ahsan

Challenor

et al. 1992

Brit J Clinical Pharma

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Section: Discussionmentioning

confidence: 99%

The influence of posture on the pharmacokinetics of orally administered nifedipine.

Renwick

Ahsan

Challenor

et al. 1992

Brit J Clinical Pharma

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“…With regard to human P450IIIA, the polymorphism exhibited at the level of enzyme activity (nifedipine oxidase) (Kleinbloesem et al, 1984) could actually reflect some variation in exposure to environmental inducers. In this respect, an evaluation of the increase in 6,-hydroxycortisol/ free cortisol urinary ratio after the administration of a standard dose of any convenient P450IIIA inducer might be a useful tool in a large population study designed to determine whether P450IIIA inducibility is genetically controlled.…”

Section: Discussionmentioning

confidence: 99%

The increase in urinary excretion of 6 beta‐hydroxycortisol as a marker of human hepatic cytochrome P450IIIA induction.

Ged

Rouillon

Pichard

et al. 1989

Brit J Clinical Pharma

310

156

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1. Urinary excretion of 6 beta‐hydroxycortisol, hepatic microsomal cortisol 6 beta‐hydroxylase and the specific content of several forms of cytochrome P450 were measured in 8 to 14 patients before and after treatment with rifampicin (600 mg orally per day for 4 days). 2. Rifampicin treatment produced an average five fold increase in daily excretion of urinary 6 beta‐hydroxycortisol. 3. Cortisol 6 beta‐ hydroxylase activity increased from 15 +/‐ 6 pmol min‐1 mg‐1 in organ donors (considered as 'control subjects') to 87 +/‐ 31 pmol min‐1 mg‐1 in rifampicin treated patients. 4. Among three forms of human P450 (P450IA, IIC and IIIA), (1), (2), measured by Western blots, only P450IIIA was significantly induced by the antibiotic. 5. Only antibodies against P450IIIA selectively inhibited cortisol 6 beta‐ hydroxylase in human liver microsomes. 6. Cortisol 6 beta‐hydroxylase was correlated with P450IIIA specific content. 7. The urinary level of 6 beta‐hydroxycortisol correlated with liver microsomal cortisol 6 beta‐ hydroxylase and P450IIIA specific content. 8. We conclude that P450IIIA is predominantly responsible for cortisol 6 beta‐hydroxylase activity in human liver microsomes and that urinary 6 beta‐hydroxycortisol is a marker of the induction of this cytochrome P450.

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“…Variability in the pharmacokinetics of nifedipine is also considerable, and has tentatively been ascribed to differences in the intrinsic metabolic capacity of oxidative enzymes in the liver (Kleinbloesem et al, 1984). The cytochrome P-450 subunit which is responsible for the metabolism of nifedipine has been isolated (Guengerich et al, 1986), but there is still some discrepancy between in vivo and in vitro data (Kalow, 1987).…”

Section: Discussionmentioning

confidence: 99%

The contribution of nisoldipine‐induced changes in liver blood flow to its pharmacokinetics after oral administration.

Harten

Burggraaf

Danhof

et al. 1989

Brit J Clinical Pharma

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1. The pharmacokinetics of nisoldipine (10 mg) was assessed in 10 healthy subjects after single dose and multiple dose oral administration. Apparent liver blood flow was measured, using ICG before and during the absorption phase of nisoldipine. 2. Apparent liver blood flow was increased both on acute and short‐term administration of nisoldipine, basal flow being lower on multiple dosing than on acute administration (P less than 0.02). 3. A positive relationship was found between the increase in apparent liver blood flow during absorption of nisoldipine and the flow‐dependent part of the total AUC of nisoldipine. 4. The findings of this study indicate that a variable liver blood flow response during the absorption phase of nisoldipine contributes to the pharmacokinetic variability of the drug, both on acute and multiple dose administration.

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Variability in nifedipine pharmacokinetics and dynamics: A new oxidation polymorphism in man

Cited by 173 publications

References 4 publications

The influence of posture on the pharmacokinetics of orally administered nifedipine.

The influence of posture on the pharmacokinetics of orally administered nifedipine.

The increase in urinary excretion of 6 beta‐hydroxycortisol as a marker of human hepatic cytochrome P450IIIA induction.

The contribution of nisoldipine‐induced changes in liver blood flow to its pharmacokinetics after oral administration.

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