Drug Input Rate from the GI-Tract. Michaelis-Menten Kinetics and the Bioavailability of Slow-Release Verapamil and Nifedipine

Woodcock, Barry G.; Menke, G; Fischer, A; Köhne, H.; Rietbrock, N.

doi:10.1007/978-3-322-91091-2_16

Cited by 3 publications

(2 citation statements)

References 12 publications

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“…Indeed, if an 80‐mg dose of verapamil is dissolved in 200 mL of intestinal fluid, this yields verapamil concentrations of about 820 μmol/L, by far exceeding the K m values for verapamil N ‐dealkylation and N ‐demethylation in human enterocytes (45 μmol/L and 41 μmol/L, respectively) 8 . Moreover, there are reports of higher bioavailability of immediate‐release compared with slow‐release formulations 20 , 21 , 22 , 23 . However, it should be noted that the latter data were usually generated by use of different dosages (or dosing regimens) for immediate‐release and slow‐release formulations.…”

Section: Discussionmentioning

confidence: 99%

Impact of concentration and rate of intraluminal drug delivery on absorption and gut wall metabolism of verapamil in humans

Glaeser

Drescher

Hofmann

et al. 2004

Clinical Pharmacology & Therapeutics

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Section: Discussionmentioning

confidence: 99%

Impact of concentration and rate of intraluminal drug delivery on absorption and gut wall metabolism of verapamil in humans

Glaeser

Drescher

Hofmann

et al. 2004

Clinical Pharmacology & Therapeutics

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“…The present report describes investigations carried out with a new slow-release tablet containing 60 mg of nifedipine embedded in a fatty-alcohol matrix, and having an in vitro release rate of about half that of currently marketed slow release formulations [4]. Bioavailability studies in healthy subjects and measurement of ambulatory blood pressure using intra-arterial recording have indicated that the in vivo release rate is not greatly different from that of GITS [5].…”

mentioning

confidence: 99%

24-hour anti-ischaemic action with once daily nifedipine

Woodcock

Thürmann

Pfleiderer

et al. 1992

Eur J Clin Pharmacol

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The ability of a fatty-alcohol matrix, slow-release tablet of nifedipine 60 mg to maintain a 24-hour anti-ischaemic action in the fixed dose of 60 mg once daily has been investigated in a randomised, placebo-controlled, double-blind trial. 12 normotensive patients with angiographically proven coronary artery disease (stenosis of at least one major vessel > or = 70%) were studied. The anti-ischaemic response was assessed over a period of 4 days as changes in the exercise-induced ST-segment depression 6 h and 24 h post-dose, and ST-segment changes in 24-h ambulatory ECGs. A measurable anti-ischaemic response was observed in 8 of the 12 patients. Exercise-induced ST-segment depression 6 h after the administration of nifedipine was reduced by 30% compared to placebo, and there was still a measurable anti-ischaemic response 24-h post-dosing. Both responses were independent of changes in exercise blood pressure. In 7 patients with ischaemic episodes in the 24-h ECGs, nifedipine treatment had only a minor effect on the intensity and duration of ischaemia. It is concluded that a significant anti-ischaemic effect lasting 24 h could be demonstrated using effort-induced ST-segment changes in patients with angiographically proven coronary heart disease, who were treated once daily with nifedipine 60 mg as a fatty-alcohol slow release tablet.

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Bioequivalence of Chiral Drugs

Mehvar

Jamali

1997

Clinical Pharmacokinetics

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Guidelines for bioequivalence of non-racemic pharmaceuticals are abundant in the literature. However, few guidelines exist for the bioequivalence of racemic drugs which consist of 2 or more stereoisomers. The aim of this article is to address the question of whether the bioequivalence of racemic drugs should be based on the measurement of the individual enantiomers or that of the total drug. Several pharmacokinetic-pharmacodynamic cases are examined to test the validity of extrapolating the bioequivalence of racemic drugs to that of their individual enantiomers after administration of the racemate; simulation and experimental data are presented to support these cases. It is shown that for drugs which exhibit non-linear pharmacokinetics, the results of bioequivalence studies based on the total drug may differ from those based on the individual enantiomers. Similar discrepancies can be shown for a racemic drug with linear pharmacokinetics whose enantiomers substantially differ from each other in their pharmacokinetic parameters. Therefore, it is suggested that stereospecific assays be used for these drugs. Additionally, it is recommended that for racemic drugs which undergo chiral inversion, and for most products with modified release characteristics, the bioequivalence be assessed using stereospecific assays. Conversely, for racemic drugs with linear pharmacokinetics and minimal to modest stereoselectivity in their kinetic parameters, and for those with non-stereoselective pharmacodynamics, the use of stereospecific analytical methods are not warranted. Finally, the limited, controversial literature in favour of or against the use of stereospecific assays in bioequivalence of chiral drugs are reviewed and a preliminary guideline is proposed.

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Drug Input Rate from the GI-Tract. Michaelis-Menten Kinetics and the Bioavailability of Slow-Release Verapamil and Nifedipine

Cited by 3 publications

References 12 publications

Impact of concentration and rate of intraluminal drug delivery on absorption and gut wall metabolism of verapamil in humans

Impact of concentration and rate of intraluminal drug delivery on absorption and gut wall metabolism of verapamil in humans

24-hour anti-ischaemic action with once daily nifedipine

Bioequivalence of Chiral Drugs

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