23 In the earlier stages of disease, patients with T2DM are able to secrete insulin and may even be hyperinsulinemic
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at a more usual amount of juice (200 mL, once daily for 3 d), the AUC was 330% of that with water.36 , 37 Rhabdomyolysis was also reported after 10 days concomitant consumption of fresh grapefruit.23 Lovastatin with grapefruit juice at a high level of consumption (400 mL, 3 times/d for 3 d) caused an AUC that was 500% of that with water.38 Atorvastatin, the most frequently prescribed drug in Canada in 2011, had an AUC with grapefruit juice (250400 mL, 3 times/d for 24 d) that ranged from 180% to 250% of that with water.39 41 Rhabdomyolysis has also been reported with grapefruit ingested at usual amounts (Table 2).21 23 Thus, this adverse outcome with certain statins can occur with the ingestion of much less grapefruit than was previously expressed by the US Food and Drug Administration.42 However, taking atorvastatin in the evening and drinking grapefruit juice in the morning (300 mL/d from a specific lot prepared by the Florida Department of Citrus) resulted in drug serum concentrations that were 119%126% of those seen with no consumption of grapefruit, with no evidence of skeletal muscle toxicity (e.g., elevated creatine phosphokinase, myalgia).43 In addition, pravastatin does not produce a pharmacokinetic interaction with grapefruit,39 , 40 rosuvastatin is eliminated unchanged,35 and fluvastatin is metabolized by an enzyme (cytochrome P450 2C9) that is not affected by grapefruit.35 Although staggering the ingestion of atorvastatin and grapefruit may reduce risk, substituting pravastatin, rosuvastatin or fluvastatin, or eliminating grapefruit juice from the diet, appears more preferable
