Lack of pharmacokinetic interaction between nifedipine, sparteine and phenytoin in man.

Abstract

Nifedipine, sparteine and phenytoin were administered orally to eight healthy subjects separately and as a 'cocktail' on four different occasions to investigate any kinetic interactions. All subjects were extensive metabolizers of sparteine. After drug intake plasma and urine samples were collected up to 32 h and the concentrations of parent drugs and main metabolites were measured. Clearances and formation clearances were not significantly different after single substrate and 'cocktail' administration. Low or non significant correlation coefficients were found between the oxidation of the individual substrates or formation of their metabolites. With this strategy of simultaneous administration of substrates ('cocktail') it appears possible to characterize (and correlate) activities of different cytochrome P-450 isoenzymes, without the disturbing influence of intraindividual variation of drug oxidation with time.

The karolinska cocktail for phenotyping of five human cytochrome P450 enzymes

“…A cocktail design offers several advantages through the required knowledge of drug metabolic pathways obtained in a single experimental session involving possible pharmacologic or pathophysiologic effects on enzyme induction or inhibition. Effects such as concomitant drug therapy and liver disease have been evaluated with the use of several different cocktails 2 , 3 , 4 , 5 . Another advantage with a cocktail is that environmental factors do not change during the limited time of the experiment 1 .…”

“…Effects such as concomitant drug therapy and liver disease have been evaluated with the use of several different cocktails. [2][3][4][5] Another advantage with a cocktail is that environmental factors do not change during the limited time of the experiment. 1 Limitations of the cocktail strategy are mutual interactions between the drugs and the high selectivity and sensitivity of the analytic methods required to analyze several drugs and metabolites in the same sample.…”

“Cocktail” Approaches and Strategies in Drug Development: Valuable Tool or Flawed Science?

“…Schellens et al 42 found no significant interactions in the oxidation of nifedipine, sparteine, and phenytoin and concluded that this three‐drug cocktail can be used to simultaneously characterize the activity of multiple cytochromes. Lack of significant interactions was observed among dextromethorphan, coumarin, and mephenytoin in a three‐drug cocktail for simultaneous evaluation of CYP2C19, CYP2D6, and CYP2A6 43…”

Calcium Antagonists

“…Patients on anticonvulsant treatment will require substantially higher doses of felodipine to achieve plasma concentrations equivalent to those in patients not taking enzymeinducing agents. [9,18] Schellens et al [25] reported the lack of a pharmacokinetic interaction between phenytoin and nifedipine. [9,18] Schellens et al [25] reported the lack of a pharmacokinetic interaction between phenytoin and nifedipine.…”