We have with interest read the paper by Vincent et al.[1] published very recently in the journal. We agree with their conclusion that grapefruit juice has no appreciable effect on amlodipine pharmacodynamics and pharmacokinetics in patients in general. We did in a paper some years ago show a pharmacokinetic interaction between amlodipine and grapefruit juice in healthy volunteers [2]. Cmax as well as AUC were significantly (P < 0.05) higher when amlodipine 5 mg was administered with grapefruit juice than with water. However, as in the paper by Vincent et al. there was no difference in BP or HR when amlodipine was taken together with grapefruit juice compared with when it was taken with water.
Vincent et al. refers to our paper and state that since we used a dose of 5 mg our analytical method was operating near the detection limit for amlodipine concentration and that this increased the variability of our results. In our method the limit of quantification was 0.2 ng ml−1 and the coefficient of variation was below 15%, i.e. the same as for the method used by Vincent et al. Vincent et al. do not discuss at all the interindividual variation in the pharmacokinetics due to biological factors. It has been shown in earlier studies that there is a variation in the pharmacokinetics of amlodipine including the bioavailability, which has been shown to vary between 52 and 85% in healthy volunteers [3]. Between patients the variations can be expected to be even larger. This variation is of far greater importance than the variations of the analytical methods. It also worth noting that in the paper by Vincent et al. pharmacokinetic data are presented for only half of the 20 individuals as far as oral administration is concerned. In our study none of the volunteers was excluded.
In our opinion, considering the individual variation in the pharmacokinetics of amlodipine it might be concluded that the possible interaction between grapefruit juice and amlodipine cannot be neglected in the clinical setting even though this interaction does not seem to be of great clinical significance in studies performed on healthy volunteers.
References
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