Saquinavir Grapefruit juice

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... 

Kupferschmidt HH, Fattinger KE, Ha HR, Follath F, Krahenbuhl S. Grapefruit juice enhances the bioavailability of the HIV protease inhibitor saquinavir in man. Br J Clin Pharmacol 1998 45(4) 355-359. 

Eagling VA, Profit L, Back DJ. Inhibition of the CYP3A4-mediated metabolism and P-glycoprotein-mediated transport of the HIV-1 protease inhibitor saquinavir by grapefruit juice components. Br J Clin Pharmacol 1999 48(4) 543-552. 

Grapefruit juice has also been shown to inhibit CYP3A4 and P-gp in the small intestine, and hence, can elevate the oral bioavailability of lipophilic drugs [98,99]. Concomitant intake of grapefruit juice with the lipophilic cholesterol-lowering medication simvastatin caused a 16-fold increase in the AUC of simvastatin [100]. The oral bioavailability of the lipophilic HIV protease inhibitor saquinavir was doubled following concomitant administration with grapefruit juice [101]. 

A Atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin Amprenavir, aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice", verapamil Cimetidine... 

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. 

SAQUINAVIR (INVIRASE HARD CAPSULES) GRAPEFRUIT JUICE Possibly t efficacy Possibly t bioavailability 1 presystemic metabolism. Constituents of grapefruit irreversibly inhibit intestinal cytochrome CYP3A4. Transport via P-gp and MRP-2 efflux pumps is also inhibited No dose adjustment is advised. Oral bioavailability is very low and is enhanced beneficially with grapefruit juice or grapefruit. Soft gel capsules have greater bioavailability so may interact to a lesser degree... 

Clinically important, potentially hazardous interactions with alcohol, aprepitant, clarithromycin, CNS depressants, delavirdine, digoxin, efavirenz, fluconazole, fluoxetine, fluvoxamine, grapefruit juice, indinavir, itraconazole, ivermectin, kava, ketoconazole, propoxyphene, ritonavir, saquinavir, St John s wort... 

Clinically important, potentially hazardous interactions with amphetamines, aprepitant, astemizole, atazanavir, azithromycin, azole antifungals, clarithromycin, darunavir, dirithromycin, erythromycin, fluoxetine, fosamprenavir, grapefruit juice, imatinib, indinavir, itraconazole, ketoconazole, methylphenidate, nefazodone, nelfinavir, nilotinib, pemoline, phenothiazines, protease inhibitors, quinidine, ritonavir, saquinavir, sertraline, sparfloxacin, sulpiride, telithromycin, thioridazine, tipranavir, tricyclic antidepressants, troleandomycin, voriconazole, zileuton, ziprasidone... 

---