Atorvastatin pharmacokinetics

Yang B-B, Siedlik PH, Smilhers JA, Sedman AJ, Stem RH. Atorvastatin pharmacokinetic interactions with other CYP3A4 substrates erythromycin and ethinyl estradiol. Pharm Res ( 996) 13 (9 Suppl), S-437. 

Stem RH, Gibson DM, Whitfield LR. Cimetidine does not alter atorvastatin pharmacokinetics or LDL-cholesterol reduction, EurJ Clin Pharmacol (1998) 53, 475-8. 

In a randomised study, two groups of 12 healthy subjects were given atorvastatin 10 mg daily for 8 days with azithromycin 500 mg daily or placebo for the final 3 days. When the azithromycin group were compared with the placebo group no change in atorvastatin pharmacokinetics were noted. ... 

An isolated case of rhabdomyolysis occurred in a patient taking tacrolimus with simvastatin. Tacrolimus does not appear to affect atorvastatin pharmacokinetics. 

Increases in exposure were reported for atorvastatin (84,154), lovastatin (155,156), and simvastatin (85,87,157). GFJ was shown not to have an effect on the pharmacokinetics of pravastatin (84,154). Atorvastatin exhibited a moderate interaction with GFJ regarding the overall exposure. Lovastatin and simvastatin exhibited a strong interaction. Pravastatin could be chosen as an alternative drug if patients want to ensure a lack of interaction. 

Fukazawa I, Uchida N, Uchida E, Yasuhara H. Effects of grapefruit juice on pharmacokinetics of atorvastatin and pravastatin in Japanese. Br J Clin Pharmacol 2004 57(4) 448 55. 

The pharmacokinetic profiles of these agents suggested that esomeprazole had inhibited P glycoprotein, reducing the normal first-pass clearance of atorvastatin (32). 

Kantola T, Kivisto KT, Neuvonen PJ. Effect of itraconazole on the pharmacokinetics of atorvastatin. Clin Pharmacol Ther 1998 64(l) 58-65. 

Stern RH, Smithers JA, Olson SC. Atorvastatin does not produce a clinically significant effect on the pharmacokinetics of terfenadine. J Clin Pharmacol 1998 38(8) 753-7. 

The effects of itraconazole, a potent inhibitor of CYP3A4, on the pharmacokinetics of atorvastatin, ceri-vastatin, and pravastatin have been evaluated in an open, randomized, crossover study in 18 healthy subjects who took single doses of atorvastatin 20 mg, cerivastatin 0.8 mg, or pravastatin 40 mg, with and without itraconazole 200 mg (72). Itraconazole markedly raised atorvastatin plasma concentrations (2.5-fold) and produced modest rises in the plasma concentrations of cerivastatin (1.3-fold) and pravastatin (1.5-fold). These results suggest that in patients taking itraconazole, cerivastatin or pravastatin may be preferable to atorvastatin. 

Healthy volunteers were given protease inhibitors and statins, and the authors concluded that simvastatin should be avoided and that atorvastatin could be used with caution in people taking ritonavir and saquinavir (111). Dosage adjustment of pravastatin may be necessary with co-administration of ritonavir and saquinavir. Pravastatin does not alter the pharmacokinetics of nelfinavir, and thus appears to be safe for co-administration. 

Mazzu AL, Lasseter KC, Shamblen EC, Agarwal V, Lettieri J, Sundaresen P. Itraconazole alters the pharmacokinetics of atorvastatin to a greater extent than either cerivastatin or pravastatin. Clin Pharmacol Ther 2000 68(4) 391 100. 

Lennernas, H. 2003. Clinical pharmacokinetics of atorvastatin. Clin Pharmacokinet 42 1141. 

The reported pharmacokinetic properties of atorvastatin calcium are summarized in Table 1.8 [3, 32, 33],... 

Md.K. Pasha, S. Muzeeb, S.J.S. Basha, D. Shashikumar, R. Mullangi, N.R. Srinivas, Analysis of five HMG-CoA reductase inhibitors—atorvastatin, lovastatin, pravastatin, rosuvastatin and simvastatin pharmacological, pharmacokinetic and analytical overview and development of a new method for use in pharmaceutical formulations analysis and in vitro metabolism studies, Biomed. Chromatogr. 20 (2006) 282-293. 

V. Borek-Dohalsky, J. Huclova, B. Barrett, B. Nemec, I. Ulc, I. Jelinek, Validated HPLC-MS-MS method for simultaneous determination of atorvastatin and 2-hydroxyatorvas-tatin in human plasma-pharmacokinetic study, Anal. Bioanal. Chem. 386 (2006) 275-285. 

Sarich TC, Schutzer KM, Dorani H, et al. No pharmacokinetic or pharmacodynamic interaction between atorvastatin and the oral direct thrombin inhibitor ximelagatran. J Clin Pharmacol 2004 44 928-934. 

Midazolam is metabolized by CYP3A4, as is atorvastatin. In a matched-pair study the effects of long-term atorvastatin on the pharmacokinetics of midazolam 0.15 mg/kg intravenously as a single dose were studied in 14 patients undergoing general anesthesia for elective surgery (56). Atorvastatin significantly reduced the clearance of midazolam by 33% and increased the AUC by 40%. 

McDonnell CG, Harte S, O DriscollJ, O Loughlin C, Van Pelt FD, Shorten GD. The effects of concurrent atorvastatin therapy on the pharmacokinetics of intravenous midazolam. Anaesthesia 2003 58 899-904. 

From an analysis of changes in ciclosporin clearance and systemic availability obtained from the medical records of 100 transplant patients, atorvastatin, fluvastatin, pravastatin, and simvastatin were found to affect ciclosporin pharmacokinetics (228). 

Hsyu PH, Schultz-Smith MD, Lillibridge JH, Lewis RH, Kerr BM. Pharmacokinetic interactions between nelfinavir and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors atorvastatin and simvastatin. Antimicrob Agents Chemother 2001 45(12) 3445-50. 

There has been a study of the effects of ritonavir 400 mg bd plus saquinavir soft-gel capsules 400 mg bd on the pharmacokinetics of pravastatin, simvastatin, and atorvas-tatin (40 mg/day each), and of the effect of pravastatin on the pharmacokinetics of nelfinavir in a randomized, open study in 56 healthy HIV-negative adults (46). Ritonavir - -saquinavir reduced the steady-state AUC of pravastatin, markedly increased the AUC of simvastatin, and slightly increased the AUC of total active atorvastatin. The AUCs of nelfinavir and its active M8 metabolite were not altered by pravastatin. The authors concluded that simvastatin (and by implication lovastatin, which in... 

Terfenadine is normally metabolized by CYP3A4 to fexofenadine, which has negligible cardiac effects. Atorvastatin is also a CYP3A4 substrate, and its effects on the pharmacokinetics of terfenadine have been studied in healthy volunteers who took atorvastatin 80 mg/day from 7 days before to 2 days after terfenadine 120 mg (8). Concentrations of terfenadine and fexofenadine were measured for 72 hours. There were no alterations in the pharmacokinetics of the parent compound or of its metabolite and there were no alterations in QTc intervals after terfenadine alone or with atorvastatin. 

Keskitalo JE, Zolk O, Fromm MF, Kurkinen KJ, Neuvonen PJ, Niemi M (2009) ABCG2 polymorphism markedly affects the pharmacokinetics of atorvastatin and rosuvastatin. Clin Pharmacol Ther 86 197-203... 

Asberg, A., Hartmann, A., Fjeldsa, E., Bergan, S. and Holdaas, H. (2001) Bilateral pharmacokinetic interaction between cyclosporine A and atorvastatin in renal transplant recipients. American Journal of Transplantation, 1, 382—386. 

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