ljm wrote:
By the way, the bottle of Lipitor I got prescribed before I departed Canada for US (guessing that I would have somewhat more difficulty here finding a off-labelling doctor) has as the sole warning on label that it must not be taken with....grapefruit or grapefruit juice. Could this have been a misprint?
That's unlikely. Grapefruit juice inhibits the enzyme Cytochrome P-450 which, if I remember correctly, normally breaks down certain drugs and compounds to make them less toxic. Thus, the dosage normally given is higher than it would otherwise be in order to compensate for the activity of this enzyme. Taking certain drugs with grapefruit could lead to an overdose. With drugs which have a potential to damage the liver, such as statins, avoiding overdoses is preferable. Here's a related paper which covers grapefruit and oral methylprednisolone...
Quote:
Grapefruit juice can increase the plasma concentrations of oral methylprednisolone. 2002.
Eur J Clin Pharmacol. 56(6-7): 489-93.OBJECTIVE: To investigate whether the pharmacokinetics of orally administered methylprednisolone and plasma cortisol concentrations are affected by administration of grapefruit juice. METHODS: In a randomised, two-phase, cross-over study, ten healthy subjects received either 200 ml double-strength grapefruit juice or water three times a day for 2 days. On day 3, 16 mg methylprednisolone was given orally with 200 ml grapefruit juice or water. Additionally, 200 ml grapefruit juice or water was ingested 0.5 h and 1.5 h after methylprednisolone administration. Plasma concentrations of methylprednisolone and cortisol were determined using liquid chromatography/mass spectrometry (LC/MS/MS) over a 47-h period. RESULTS: Grapefruit juice increased the total area under the plasma methylprednisolone concentration-time curve (AUC 0--infinity) by 75% (P < 0.001) and the elimination half-life (t1/2) of methylprednisolone by 35% (P < 0.001). The peak plasma concentration of methylprednisolone (Cmax) was increased by 27% (P < 0.01). Grapefruit juice delayed the time to the Cmax from 2.0 h to 3.0 h (P < 0.05). There was no significant difference in the plasma cortisol concentrations, measured after methylprednisolone administration, between the water and grapefruit juice phases. However, grapefruit juice slightly decreased the morning plasma cortisol concentrations before methylprednisolone administration (P < 0.05). CONCLUSIONS: Grapefruit juice given in high amounts moderately increases the AUC 0--infinity and t1/2 of oral methylprednisolone. The increase in t1/2 suggests that grapefruit juice can affect the systemic methylprednisolone metabolism. The clinical significance of the grapefruit juice-methylprednisolone interaction is small, but in some sensitive subjects high doses of grapefruit juice might enhance the effects of oral methylprednisolone.
In the above article, enhancing the effects of methylprednisolone may not be dersirable as it could lead to oversuppression of the immune system. Concerning statins, there apparently is an increased risk for statin-induced rhabdomyolysis, i.e., break down of muscle tissue. This releases myoglobin into the bloodstream which is toxic to the kidneys and can lead to kidney failure.
Statin-associated rhabdomyolysis triggered by grapefruit consumption.
Neurology. 2004 Feb 24;62(4):670.
Pharmacological comparison of the statins.
Arzneimittelforschung. 2003;53(9):605-11
Cytochrome P450 drug interactions within the HMG-CoA reductase inhibitor class: are they clinically relevant?
Drug Saf. 2003;26(1):13-21.
Effects of regular consumption of grapefruit juice on the pharmacokinetics of simvastatin.
Br J Clin Pharmacol. 2004 Jul;58(1):56-60.
Quote:
RESULTS: Grapefruit juice increased the area under the plasma concentration-time curves from 0 to 24 h [AUC(0-24)] of simvastatin 3.6-fold (range 1.8-6.0-fold; P < 0.01) and that of simvastatin acid 3.3-fold (range 2.1-5.6-fold; P < 0.01), respectively. The peak concentrations (C(max)) of simvastatin and simvastatin acid were increased 3.9-fold (range 2.3-9.3-fold; P < 0.01) and 4.3-fold (range 2.7-7.9-fold; P < 0.01) by grapefruit juice. CONCLUSIONS: Even one glass of grapefruit juice, taken daily, considerably increases the plasma concentrations of simvastatin and simvastatin acid. Grapefruit juice may increase both the cholesterol-lowering effect and the risk of adverse effects of simvastatin.
NHE
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