P-glycoprotein inhibition

Rautio, J., Humphreys, J.E., Webster, L. O., Balakrishnan, A., Keogh, J.P., Kunta, J.R., Serabjit-Singh, C.J. and Polli, J.W. (2006) In vitro P-glycoprotein inhibition assays for assessment of clinical drug interaction potential of new drug candidates a recommendation for probe substrates. Drug Metabolism and Disposition, 34, 786-792. 

Zhu HJ, Wang JS, Markowitz JS, Donovan JL, Gibson BB, Gefroh HA, Devane CL (2006) Characterization of P-glycoprotein inhibition by major cannabinoids from marijuana. J Pharmacol Exp Ther 317 850-857. 

Sadeque, A.J., Wandel, C., He, H., Shah, S., and Wood, A.J. (2000) Increased drug delivery to the brain by P-glycoprotein inhibition. Clin Pharmacol Ther 68 231-237. 

Foster BC, Foster MS, Vandenhoek S, et al. An in vitro evaluation of human cytochrome P450-3A4 and P-glycoprotein inhibition by garlic. J Pharm Pharmaceut Sci 2001 4 176-184. 

Kimura, Y., et al. 2002. P-glycoprotein inhibition by the multidrug resistance-reversing agent MS-209 enhances bioavailability and antitumor efficacy of orally administered paclitaxel. Cancer Chemother Pharmacol 49 322. 

Verstuyft, C., et al. 2003. Dipyridamole enhances digoxin bioavailability via P-glycoprotein inhibition. Clin Pharmacol Ther 73 51. 

Perloff, M.D., et al. 2003. Rapid assessment of P-glycoprotein inhibition and induction in vitro. Pharm Res 20 1177. 

Gerrard G., Payne E., Baker R.J., Jones D.T., Potter M., Prentice H.G. (2004) Clinical effects and P-glycoprotein inhibition in patients with acute myeloid leukaemia treated with zosuquidar trihydrochloride, daunorubicin and cytarabine, Haematologica 89 782-790. 

WangE,Barecki-RoachM, Johnson WW. Quantitative characterization of direct P-glycoprotein inhibition by St. John s wort constituents hypericin and hyperforin. J Pharm Pharmacol 2004 56 123-128. 

Table 12.1 Effect of P-glycoprotein inhibition on the extraction ratios of drugs across CYP3A4-overexpressing Caco-2 monolayers [13, 14],...

Golstein PE, Boom A, van Geffel J, Jacobs P, Masereel B, Beauwens R. P-glycoprotein inhibition by glibenclamide and related compounds. Pflugers Arch 1999 437 652-660. 

It seems probable that clarithromycin, erythromycin and troleandomycin, and to a lesser extent some of the other macrolides, slow the rate of metabolism of the carbamazepine by the cytochrome P450 isoenzyme CYP3A4 so that the anticonvulsant accumulates within the body." " Telithromycin is predicted to interact similarly." It was suggested that the carbamazepine toxicity seen with roxithromycin may have been mediated by P-glycoprotein inhibition, which occurred as a result of an interaction between roxithromycin and atorvastatin. 

Verstujrft C, Strabach S, El Morabet H, Kerb R, Brinkmam U, Dubert L, Jaillon P, Funck-Brentano C, Trugnan G, BecquemontL. Dip5frid ole enhances digoxin bioavailabiUty via P-glycoprotein inhibition. Clin Pharmacol Ther (2003) 73, 51-60. 

Quinidine reduces the renal excretion of digoxin by 40 to 50%, and it also appears to have some effects on non-renal clearance, which includes a reduction in digoxin excretion in the bile. There is also evidence that increases in the rate and extent of absorption of digoxin from the gut occur. More recent studies show that the mechanism behind these effects on absorption and renal excretion is likely to be P-glycoprotein inhibition by quinidine.Digoxin also appears to cause a small reduction in the renal clearance of quinidine. Quinidine appears to increase digitoxin serum levels by reducing its non-renal clearance. 

It was suggested that the effect of polyethylene glycol on digoxin was via P-glycoprotein inhibition, see also Digitalis glycosides + Surfactant excipients , p.941. 

Azithromycin is believed to be metabolised by routes independent of the cytochrome P450 enzyme system. Intravenous azithromycin was thought to have increased ciclosporin levels through P-glycoprotein inhibition and/or competition for biliary excretion in one case report. ... 

It appears that ciclosporin inhibits the metabolism of sirolimus by the cytochrome P450 isoenzyme CYP3A4 in the gut and liver leading to increased sirolimus levels. P-glycoprotein inhibition may also eontrib-ute to the interaction. 

Choi DH, Chung JH, Choi IS. Pharmacokinetic interaction between oral lovastatin and verapamil in healthy subjects. Role of P-glycoprotein inhibition by lovastatin. Eur J Clin Pharmacol 2010 66 285-90. 

Collnot EM, Baldes C, Schaefer UF, Edgar KJ, Wempe MF (2010) Vitamin E TPGS P-glycoprotein inhibition mechanism influence on conformational flexibility, intracellular ATP levels, and role of time and site of access. Mol Pharm 7 642-651... 

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