Midazolam grapefruit juice

Kupferschmidt, H. H. T., Riem, H., Ziegler, W. H., Meier, P. J., Krahenbuhl, S., Interaction between grapefruit juice and midazolam in humans, Clin. Pharmacol. Ther. 1995, 58, 20-28. 

Fig. 18.6. Midazolam administration with and without grapefruit juice (CFJ) treatment [41]. Midazolam (15 mg tablet) was administered to eight male subjects (average body weight 82 kg) before and after consumption of two glasses (200 mL each) of CFJ, 1 h before drug administration. QMPRPIus was used to estimate human effective permeability (12 x 10 4 cm s 1), pure aqueous water...

In vitro kinetic constants obtained from homogenate or whole-cell experiments under controlled conditions were used, and the constants were scaled to the in vivo scenario using appropriate physiological scale factors. Figure 18.6 shows our simulated results for absorption and metabolism of midazolam when dosed with and without grapefruit juice. Midazolam is metabolized by the gut and liver by cytochrome 3A4. Saquinavir is also metabolized in the gut and liver by 3A4, and it is also a substrate for efflux by P-gp. Figure 18.7 shows our simulated results for absorption and metabolism of saquinavir when dosed with and without grapefruit juice. In both cases, it can be seen that the simulation correctly predicts the... 

Tobacco and rifampin both induce hepatic enzymes, which may decrease the duration of action of the BZs. Grapefruit juice has received recent recognition as a factor in the pharmacokinetics of many drugs. Grapefruit juice slows down the GI absorption of midazolam and also decreases biotransformation, which leads to a delayed onset of effect and an increase in drowsiness (Ameer and Weintraub, 1997). 

Kupferschmidt HHT, Ha HR, Ziegler WH, et al. Interaction between grapefruit juice and midazolam in humans. Clin Pharmacol Ther 1995 58 20-28. 

Farkas D, Oleson LE, Zhou Y, et al. Pomegranate juice does not impair clearance of oral or intravenous midazolam, a probe for cytochrome P450-3A activity comparison with grapefruit juice. J Clin Pharmacol 2007 47 286-294. 

Cytochrome P450 3A4 is highly expressed in the human small intestinal mucosa, and is responsible for the metabolism of cyclosporine, midazolam, clozapine and saquinavir during passage across the intestinal mucosa. Indeed, inhibition of presystemic metabolic processes is likely to be a factor in a 34% to 103% increase in the bioavailability of nifedipine observed in individuals consuming grapefruit juice. 

Grapefruit juice reduced the metabolism of midazolam prolonged sedation can be expected in some circumstances (60). 

D Arcy PF. Grapefruit juice, midazolam and triazolam. Int Pharm J 1996 10 223. 

ALPRAZOLAM, DIAZEPAM, MIDAZOLAM-ORAL GRAPEFRUIT JUICE Possibly t efficacy and t adverse effects, e.g. sedation, CNS depression Possibly t bioavailability, 1 presystemic metabolism. Constituents of grapefruit juice irreversibly inhibit intestinal CYP3A4. Transport via P-gp and MRP-2 efflux pumps is also inhibited Avoid concomitant use. Be particularly vigilant in elderly patients or those with impaired liver function. Consider alternative, e.g. temazepam... 

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