Atorvastatin Rifampicin

In a randomized crossover study rifampicin reduced the total AUC of atorvastatin and increased the Qnax of 2-hydroxyatorvastatin acid by 68% (101). It is advisable to increase the dosage of atorvastatin and preferable to administer it in the evening to guarantee adequate concentrations during the period of rapid cholesterol synthesis that occurs at night when rifampicin or other potent inducers of CYP3A4 are co-administered. 

Figure 12.2 Mean ( ) SD plasma concentrations of (a) atorvastatin, (b) 2-OH ATV, and (c) 4-OH ATV in rats (n = 5) after a single oral dose of 10 mg/kg atorvastatin with and without rifampicin given as a bolus intravenous dose (20mg/kg). Solid circles indicate the ATV-alone control group open circles indicate the RIF-treatment group. Data are depicted on a semilogarithmic scale. After Ref. [28].

Lau, Y.Y., Okochi, H., Huang. Y.. and Benet, L.Z. (2006) Pharmacokinetics of atorvastatin and its hydroxyl metabolites in rats and the effects of concomitant rifampicin single doses relevance of... 

OATPIBI (OATP-C/OATP2) Atorvastatin, Cerivastatin, Fluvastatin, Benzylpenicillin, Rifampicin... 

Rifampicin lowers the serum levels of atorvastatin, fluvastatin, pravastatin, and simvastatin. 

Especially the inhibition or induction of cytochrome P450 subtype 3A4 (CYP 3A4) is clinically relevant, because a variety of active substances and food substances (e.g. grapefruit juice) are able to affect this enzyme. Substances inhibiting CYP 3A4 include ciclosporin, dihydropyridines, verapamil, midazolam, paclitaxel, simvastatin, lovastatin, atorvastatin, cimetidine, erythromycin, troleandomycin, ketoconazole (and other azoles). Substances inducing CYP 3A4 include steroids, rifampicin, phenobarbital and St John s wort. 

Drug interactions The extent to which vitamin D supplementation alters drug effectiveness and toxicity in humans has been systematically reviewed. Bile acid sequestrants and lipase inhibitors were found to inhibit the absorption of vitamin D from the gut. Statins, rifampicin, isoniazid, hydroxychloroquine, antiepileptics, corticosteroids, immimo-suppressive and chemotherapeutic agents, antiretroviral drugs and H2 receptor antagonists interfered with vitamin D metabolism. The interaction between vitamin D and thiazide diuretics could result in hypercalcaetnia. Vitamin D supplementation decreases concentrations of atorvastatin, and could cause hypercalcaetnia in elderly individuals or tixose with compromised renal function or hyperparathyroidism [84 ]. 

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