To: Zebra 365 who wrote (793 ) 3/29/1998 4:27:00 PM From: Zebra 365 Read Replies (3) | Respond to
Viagra and Grapefruit, caution.....I bet a lot of physicians don't even know that because it is new research, 1997-8, found after some empirical evidence suggested it. The package insert on Sporonox now warns about this interaction.Sildenafil metabolism is principally mediated by the cytochrome P450 (CYP) isoforms 3A4 (major route) and 2C9 (minor route). Therefore, inhibitors of these isoenzymes may reduce sildenafil clearance. ------------ Okey Dokey, Because of the "timing factor" for sildenafil action --could you get me that picture of Pammy, Dear?--it would seem to me that concomittant use of drugs that raise sildenafil serum levels would raise the incidence of side effects more than any impact of its increasing the erectile response. Any pharmacists want to jump in?>>> ncbi.nlm.nih.gov .1998 ;62(10):PL135-PL142 Mechanism-based inactivation of human cytochrome P450 3A4 by grapefruit juice and red wine. Grapefruit juice is well documented to cause clinically significant increases in the plasma concentrations of many therapeutic agents. These interactions are believed to be mediated via inhibition of intestinal cytochrome P-450 3A4 (CYP3A4) by flavonoids and/or other chemicals in grapefruit juice , although the mechanism of that inhibition has not been fully characterized. Like grapefruit juice, red wine contains large amounts of flavonoids and other xenobiotics which could also mediate CYP3A4 inhibition. In this study, we investigated the mechanism of inhibition of CYP3A4 by grapefruit juice and also examined the ability of red wine to inhibit this enzyme. Both red wine and grapefruit juice potently inhibited CYP3A4 activity in a concentration-dependent manner. At 8% of natural strength, enzyme activity was inhibited almost 90 and 84%, respectively, by grapefruit juice and red wine. In contrast, white wine did not appreciably inhibit CYP3A4 activity. Grapefruit juice irreversibly inactivated CYP3A4 in a time- and NADPH-dependent manner. The rate of inactivation mediated by grapefruit juice was similar to that mediated by troleandomycin, a potent mechanism-based inhibitor of CYP3A4. Red wine also inactivated CYP3A4 but at a rate approximately 16% that of grapefruit juice. Inhibition of CYP3A4 by red wine is primarily reversible in nature. The clinical implications of this research are discussed. This study suggests that the Cyt P450 is inhibited 90% by grapefruit juice with only 8% real grapefruit juice (it's common for commercial fruit drinks to be only about 10% real juice.) A friend of mine is a cardiologist who is very big on flavonoids, I always know when he has referred a patient to me, because they are all taking the bioflavonoids (look in your supermarket vitamin section, flavonoid supplements are available without a prescription) And now of course, we have the atherosclerotic patient as a prime target market for Viagra.I wonder if this potential interaction has been tested or will become part of the cautions to the patients? That's what Phase IV is all about.....
