Abstract
Background: Anecdotal evidence suggests that there may be sex differences in Drug-drug Interactions (DDI) involving specific drugs. Regulators have provided general guidance for the inclusion of females in clinical studies. Some clinical studies have reported sex differences in the Pharmacokinetics (PK) of CYP3A4 substrates, suggesting that DDI involving CYP3A4 substrates could potentially show sex differences.
Objective: The aim of this review was to investigate whether recent prospective DDI studies have included both sexes and whether there was evidence for the presence or absence of sex differences with the DDIs.
Methods: The relevant details from 156 drug interaction studies within 124 papers were extracted and evaluated.
Results: Only eight studies (five papers) compared the outcome of the DDI between males and females. The majority of the studies had only male volunteers. Five studies had females only while 60 had males only, with 7.7% of the studies having an equal proportion of both sexes. Surprisingly, four studies did not specify the sex of the subjects.
Based on the limited number of studies comparing males and females, no specific trends or conclusions were evident. Sex differences in the interaction were reported between ketoconazole and midazolam as well as clarithromycin and midazolam. However, no sex difference was observed with the interaction between clarithromycin and triazolam or erythromycin and triazolam. No sex-related PK differences were observed with the interaction between ketoconazole and domperidone, although sex-related differences in QT prolongation were observed.
Conclusion: This review has shown that only limited progress had been made with the inclusion of both sexes in DDI studies.
Keywords: Sex differences and DDI, drug-drug interactions, DDI with CYP 3A4 substrates, sex of subjects in DDI studies, sex and CYP3A4 inhibition.
Graphical Abstract
[1]
Federal Register Notice. The study and evaluation of gender differences in the clinical evaluation of drugs. Guideline for the study and evaluation of gender differences in the clinical evaluation of drugs. FR Notice, 1993, 58, 39406-39416.
[2]
Soldin, O.P.; Mattison, D.R. Sex differences in pharmacokinetics and pharmacodynamics. Clin. Pharmacokinet., 2009, 48(3), 143-157.
[3]
Chen, M.L.; Lee, S.C.; Ng, M.J.; Schuirmann, D.J.; Lesko, L.J.; Williams, R.L. Pharmacokinetic analysis of bioequivalence trials: Implications for sex-related issues in clinical pharmacology and biopharmaceutics. Clin. Pharmacol. Ther., 2000, 68(5), 510-521.
[4]
Cotreau, M.M.; Von Moltke, L.L.; Greenblatt, D.J. The influence of age and sex on the clearance of cytochrome P450 3A substrates. Clin. Pharmacokinet., 2005, 44(1), 33-60.
[5]
Schwartz, J.B. The influence of sex on pharmacokinetics. Clin. Pharmacokinet., 2003, 42(2), 107-121.
[6]
Bedford, T.A.; Rowbotham, D.J. Cisapride: Drug interactions of clinical significance. Drug Saf., 1996, 15(3), 167-175.
[7]
Piscitelli, S.C.; Flexner, C.; Miners, J.R.; Polis, M.A.; Masur, H. Drug interactions in patients infected with human immunodeficiency virus. Clin. Infect. Dis., 1996, 23, 685-693.
[8]
Ayrton, A.; Morgan, P. Role of transport proteins in drug absorption, distribution and excretion. Xenobiotica, 2001, 31, 469-497.
[9]
Miners, J.O.; Birkett, D.J. Cytochrome P450 2C9: An enzyme of major importance in human drug metabolism. Br. J. Clin. Pharmacol., 1998, 45(6), 525-538.
[10]
Zhou, S-F.; Xue, C.C.; Yu, X-Q.; Li, C.; Wang, G. Clinically important drug interactions potentially involving mechanism-based inhibition of cytochrome P450 3A4 and the role of therapeutic drug monitoring. Ther. Drug Monit., 2007, 29(6), 687-710.
[11]
Skerjanec, A.; Wang, J.; Maren, K.; Rojkjaer, L. Investigation of the pharmacokinetic interactions of deferasirox, a once-daily oral iron chelator, with midazolam, rifampin, and repaglinide in healthy volunteers. J. Clin. Pharmacol., 2009, 50(2), 205-213.
[12]
Thummel, K.E.; Wilkinson, G.R. In vitro and in vivo drug interactions involving human CYP3A. Annu. Rev. Pharmacol., 1998, 38, 389-430.
[13]
Venkatakrishnan, K. DDI risk assessment and evaluation in pharmaceutical development: Interfacing drug metabolism and clinical pharmacology. Encyclopedia of Drug Metabolism and
Interactions, John Wiley & Sons: New York, 2012.
[14]
Murray, M. P450 enzymes: Inhibition mechanism, genetic regulation and effects of liver disease. Clin. Pharmacokinet., 1992, 23(2), 132-146.
[15]
Vogel, M.; Voigt, E.; Michaelis, H.C.; Sudhop, T.; Wolff, M.; Türler, A.; Sauerbruch, T.; Rockstroh, J.K.; Spengler, U. Management of drug-drug interactions between cyclosporine A and the protease inhibitor lopinavir-ritonavir in liver- transplanted HIV infected patients. Liver Transpl., 2004, 10(7), 939-944.
[16]
Zimmermann, A.E.; Pizzoferrato, T.; Bedford, J.; Morris, A.; Hoffman, R.; Braden, G. Tenofovir-associated acute and chronic kidney disease: A case of multiple drug interactions. Clin. Infect. Dis., 2006, 42, 283-290.
[17]
Danton, A.C.; Montastruc, F.; Sommet, A.; Durrieu, G.; Bagheri, H.; Bondon-Guitton, E.; Lapeyre-Mestre, M.; Montastruc, J.L. Importance of cytochrome P450 (CYP450) in adverse drug reactions due to drug- drug interactions: A pharmaco-vigilance study in France. Eur. J. Clin. Pharmacol., 2012, 69(4), 885-888.
[18]
Greenblatt, D.J.; Von Moltke, L.L. Gender has a small but statistically significant effect on clearance of CYP3A substrate drugs. J. Clin. Pharmacol., 2008, 48, 1350-1355.
[19]
Chetty, M.; Mattison, D.; Rostami-Hodjegan, A. Sex differences in the clearance of CYP3A4 substrates: Exploring possible reasons for the substrate dependency and lack of consensus. Curr. Drug Metab., 2012, 13(6), 778-786.
[20]
Saari, T.I.; Laine, K.; Leino, K.; Valtonen, M.; Pertti, J.; Neuvonen, P.J.; Olkkola, K.T. Voriconazole, but not terbinafine, markedly reduces alfentanil clearance and prolongs its half‐life. Clin. Pharmacol. Ther., 2006, 80, 502-508.
[21]
Rebello, S.; Compain, S.; Feng, A.; Hariry, S.; Dieterich, H.A.; Jarugula, V. Effect of cyclosporine on the pharmacokinetics of aliskiren in healthy subjects. J. Clin. Pharmacol., 2011, 51, 1549-1560.
[22]
Tapaninen, T.; Backman, J.T.; Kurkinen, K.J.; Neuvonen, P.J.; Niemi, M. Itraconazole, a P-glycoprotein and CYP3A4 inhibitor markedly raises the plasma concentrations and enhances the renin-inhibiting effect of aliskiren. J. Clin. Pharmacol., 2011, 51, 359-367.
[23]
Vaidyanathan, S.; Camenisch, G.; Schuetz, H.; Reynolds, C.; Yeh, C.M.; Bizot, M.N.; Dieterich, H.A.; Howard, D.; Dole, W.P. Pharmacokinetics of the oral direct renin inhibitor aliskiren in combination with digoxin, atorvastatin, and ketoconazole in healthy subjects: The role of P-glycoprotein in the disposition of aliskiren. J. Clin. Pharmacol., 2008, 48, 1323-1338.
[24]
Fleishaker, J.C.; Herman, B.D.; Carel, B.J.; Azie, N.E. Interaction between ketoconazole and almotriptan in healthy volunteers. J. Clin. Pharmacol., 2003, 43, 423-427.
[25]
Greenblatt, D.J.; Von Moltke, L.L.; Harmatz, J.S.; Durol, A.L.B.; Daily, J.P.; Graf, J.A.; Mertzanis, P.; Hoffman, J.L.; Shader, R.I. Alprazolam-ritonavir interaction: Implications for product labelling. Clin. Pharmacol. Ther., 2000, 67, 335-341.
[26]
Spence, R.; Mandagere, A.; Richards, D.B.; Magee, M.H.; Dufton, C.; Boinpally, R. Potential for pharmacokinetic interactions between ambrisentan and cyclosporine. Clin. Pharmacol. Ther., 2010, 88, 513-520.
[27]
Kantola, T.; Kivistö, K.T.; Neuvonen, P.J. Effect of itraconazole on the pharmacokinetics of atorvastatin. Clin. Pharmacol. Ther., 1998, 64, 58-65.
[28]
El Mouelhi, M.; Worley, D.J.; Kuzmak, B.; Destefano, A.J.; Thompson, G.A. Influence of ketoconazole on azimilide pharmacokinetics in healthy subjects. Br. J. Clin. Pharmacol., 2004, 58, 641-647.
[29]
Lamberg, T.S.; Kivistö, K.T.; Neuvonen, P.J. Effects of verapamil and diltiazem on the pharmacokinetics and pharmacodynamics of buspirone. Clin. Pharmacol. Ther., 1998, 63, 640-645.
[30]
Johnson, B.M.; Adams, L.M.; Zhang, K.; Gainer, S.D.; Kirby, L.C.; Blum, R.A.; Apseloff, G.; Morrison, R.A.; Lebowitz, P.F. Ketoconazole and rifampin significantly affect the pharmacokinetics, but not the safety or QTc interval, of casopitant, a neurokinin-1 receptor antagonist. J. Clin. Pharmacol., 2010, 50, 951-959.
[31]
Böhmer, G.M.; Drollmann, A.; Gleiter, C.H.; Nave, R. Effect of co-administered ketoconazole, a strong cytochrome P450 3A4 enzyme inhibitor, on the pharmacokinetics of ciclesonide and its active metabolite desisobutyryl-ciclesonide. Clin. Pharmacokinet., 2008, 47, 343-349.
[32]
Robert, M.; Salvà, M.; Segarra, R.; Pavesi, M.; Esbri, R.; Roberts, D.; Golor, G. The prokinetic cinitapride has no clinically relevant pharmacokinetic interaction and effect on QT during co-administration with ketoconazole. Drug Metab. Dispos., 2007, 35(7), 1149-1156.
[33]
Ouellet, D.; Hsu, A.; Granneman, G.R.; Carlson, G.; Cavanaugh, J.; Guenther, H.; Leonard, J.M. Pharmacokinetic interaction between ritonavir and clarithromycin. Clin. Pharmacol. Ther., 1998, 64(4), 355-362.
[34]
Farid, N.A.; Payne, C.D.; Small, D.S.; Winters, K.J.; Ernest, C.S.; Brandt, J.T.; Darstein, C.; Jakubowski, J.A.; Salazar, D.E. Cytochrome P450 3A inhibition by ketoconazole affects prasugrel and clopidogrel pharmacokinetics and pharmacodynamics differently. Clin. Pharmacol. Ther., 2007, 81, 735-741.
[35]
Gomez, D.Y.; Wacher, V.J.; Tomlanovich, S.J.; Hebert, M.F.; Benet, L.Z. The effects of ketoconazole on the intestinal metabolism and bioavailability of cyclosporine. Clin. Pharmacol. Ther., 1995, 58, 15-19.
[36]
Hebert, M.F.; Townsend, R.W.; Austin, S.; Balan, G.; Blough, D.K.; Buell, D.; Keirns, J.; Bekersky, I. Concomitant cyclosporine and micafungin pharmacokinetics in healthy volunteers. J. Clin. Pharmacol., 2005, 45(8), 954-960.
[37]
Banfield, C.; Herron, J.; Keung, A.; Padhi, D.; Affrime, M. Desloratadine has no clinically relevant electrocardiographic or pharmacodynamic interactions with ketoconazole. Clin. Pharmacokinet., 2002, 41(S1), 37-44.
[38]
Jakate, A.S.; Roy, P.; Patel, A.; Abramowitz, W.; Persiani, S.; Wangsa, J.; Kapil, R. Effect of azole antifungals ketoconazole and fluconazole on the pharmacokinetics of dexloxiglumide. Br. J. Clin. Pharmacol., 2005, 60(5), 498-507.
[39]
Boyce, M.J.; Baisley, K.J.; Warrington, S. Pharmacokinetic interaction between domperidone and ketoconazole leads to QT prolongation in healthy volunteers: A randomized, placebo-controlled, double-blind, crossover study. Br. J. Clin. Pharmacol., 2011, 73(3), 411-421.
[40]
Kovarik, J.M.; Beyer, D.; Bizot, M.N.; Jiang, Q.; Shenouda, M.; Schmouder, R.L. Blood concentrations of everolimus are markedly increased by ketoconazole. J. Clin. Pharmacol., 2005, 45, 514-518.
[41]
Jalava, K.M.; Olkkola, K.T.; Neuvonen, P.J. Itraconazole greatly increases plasma concentrations and effects of felodipine. Clin. Pharmacol. Ther., 1997, 61(4), 410-415.
[42]
Malhotra, B.; Dickins, M.; Alvey, C.; Jumadilova, Z.; Li, X.; Duczynski, G.; Gandelman, K. Effects of the moderate CYP3A4 inhibitor, fluconazole, on the pharmacokinetics of fesoterodine in healthy subjects. Br. J. Clin. Pharmacol., 2011, 72(2), 263-269.
[43]
Smith, D.A.; Koch, K.M.; Arya, N.; Bowen, C.J.; Herendeen, J.M.; Beelen, A. Effects of ketoconazole and carbamazepine on lapatinib pharmacokinetics in healthy subjects. Br. J. Clin. Pharmacol., 2009, 67(4), 421-426.
[44]
Williamson, K.M.; Patterson, J.H.; McQueen, R.H.; Adams, K.F., Jr; Pieper, J.A. Effects of erythromycin or rifampin on losartan pharmacokinetics in healthy volunteers. Clin. Pharmacol. Ther., 1998, 63(3), 316-323.
[45]
Azie, N.E.; Brater, C.; Becker, P.A.; Jones, D.R.; Hall, S.D. The interaction of diltiazem with lovastatin and pravastatin. Clin. Pharmacol. Ther., 1998, 64(4), 369-377.
[46]
Neuvonen, P.J.; Jalava, K.M. Itraconazole drastically increases plasma concentrations of lovastatin and lovastatin acid. Clin. Pharmacol. Ther., 1996, 60, 54-61.
[47]
Cobb, M.N. The effects of fluconazole on the clinical pharmacokinetics of methadone. Clin. Pharmacol. Ther., 1998, 63, 655-662.
[48]
Varis, T.; Keukonen, K.M.; Kivisto, K.T.; Neuvonen, P.J. Plasma concentrations and effects of oral methylprednisolone are considerably increased by itraconazole. Clin. Pharmacol. Ther., 1998, 64(4), 363-368.
[49]
Chung, E.; Nafziger, A.N.; Kazierad, D.J.; Bertino, J.S., Jr Comparison of midazolam and simvastatin as cytochrome P450 3A probes. Clin. Pharmacol. Ther., 2006, 79(4), 350-361.
[50]
Gorski, J.C.; Jones, D.R.; Haehner‐Daniels, B.D.; Hamman, M.A.; O’Mara, E.M.; Hall, S.D. The contribution of intestinal and hepatic CYP3A to the interaction between midazolam and clarithromycin. Clin. Pharmacol. Ther., 1998, 64(2), 133-143.
[51]
Olkkola, K.T.; Backman, J.T.; Neuvonen, P.J. Midazolam should be avoided in patients receiving the systemic antimycotics ketoconazole or itraconazole. Clin. Pharmacol. Ther., 1994, 55, 481-485.
[52]
Olkkola, K.T.; Ahonen, J.; Neuvonen, P.J. The effect of the systemic antimycotics, itraconazole and fluconazole, on the pharmacokinetics and pharmacodynamics of intravenous and oral midazolam. Anesth. Analg., 1996, 82, 511-516.
[53]
Templeton, I.; Peng, C-C.; Thummel, K.E.; Davis, C.; Kunze, K.L.; Isoherranen, N. Accurate prediction of dose‐dependent CYP3A4 inhibition by itraconazole and its metabolites from in vitro inhibition data. Clin. Pharmacol. Ther., 2010, 88(4), 499-505.
[54]
Tsunoda, S.M.; Velez, R.L.; Von Moltke, L.L.; Greenblatt, D.J. Differentiation of intestinal and hepatic cytochrome P450 3A activity with use of midazolam as an in vivo probe: Effect of ketoconazole. Clin. Pharmacol. Ther., 1999, 66(5), 461-471.
[55]
Chen, M.; Nafziger, A.N.; Bertino, J.S., Jr Drug metabolizing enzyme inhibition by ketoconazole does not reduce inter individual variability of CYP3A activity as measured by oral midazolam. Drug Metab. Dispos., 2006, 34(12), 2079-2082.
[56]
Friedman, E.J.; Fraser, I.P.; Wang, Y.H.; Bergman, A.J.; Li, C.C.; Larson, P.J.; Chodakewitz, J.; Wagner, J.A.; Stoch, S.A. Effect of different durations and formulations of diltiazem on the single-dose pharmacokinetics of midazolam: how long do we go? J. Clin. Pharmacol., 2011, 51(11), 1561-1570.
[57]
Olkkola, K.T.; Aranko, K.; Luurila, H.; Hiller, A.; Saarnivaara, L.; Himberg, J.J.; Neuvonen, P.J. A potentially hazardous interaction between erythromycin and midazolam. Clin. Pharmacol. Ther., 1993, 53(3), 298-305.
[58]
Palkama, V.J.; Ahonen, J.; Neuvonen, P.J.; Olkkola, K.T. Effect of saquinavir on the pharmacokinetics and pharmacodynamics of oral and intravenous midazolam. Clin. Pharmacol. Ther., 1999, 66(1), 33-39.
[59]
Zamuner, S.; Johnson, B.M.; Pagliarusco, S.; Fina, P.; Peroni, M.; Fiore, M.; Adams, L.M.; Fernandes, S.A. Effect of single and repeat doses of casopitant on the pharmacokinetics of CYP450 3A4 substrates midazolam and nifedipine. Br. J. Clin. Pharmacol., 2010, 70(4), 621-627.
[60]
Niemi, M.; Backman, J.T.; Juntti‐Patinen, L.; Neuvonen, M.; Neuvonen, P.J. Coadministration of gemfibrozil and itraconazole has only a minor effect on the pharmacokinetics of the CYP2C9 and CYP3A4 substrate nateglinide. Br. J. Clin. Pharmacol., 2005, 60(2), 208-217.
[61]
Abbas, R.; Hug, B.A.; Leister, C.; Sonnichsen, D. Pharmacokinetics of oral neratinib during co-administration of ketoconazole in healthy subjects. Br. J. Clin. Pharmacol., 2011, 71(4), 522-527.
[62]
Jaruratanasirikul, S.; Sriwiriyajan, S. Pharmacokinetic study of the interaction between itraconazole and nevirapine. Eur. J. Clin. Pharmacol., 2007, 63(5), 451-456.
[63]
Tanaka, C.; Yin, O.Q.P.; Smith, T.; Sethuraman, S.; Grouss, K.; Harrell, R.; Schran, H.; Galitz, L. Effects of rifampin and ketoconazole on the pharmacokinetics of nilotinib in healthy participants. J. Clin. Pharmacol., 2011, 51(1), 75-83.
[64]
Böttiger, Y.; Tybring, G.; Götharson, E.; Bertilsson, L. Inhibition of the sulfoxidation of omeprazole by ketoconazole in poor and extensive metabolizers of S‐mephenytoin. Clin. Pharmacol. Ther., 1997, 62(4), 384-391.
[65]
Jaakkola, T.; Backman, J.T.; Neuvonen, M.; Neuvonen, P.J. Effects of gemfibrozil, itraconazole, and their combination on the pharmacokinetics of pioglitazone. Clin. Pharmacol. Ther., 2005, 77(5), 404-414.
[66]
Kaukonen, K.M.; Olkkola, K.T.; Neuvonen, P.J. Itraconazole increases plasma concentrations of quinidine. Clin. Pharmacol. Ther., 1997, 62(5), 510-517.
[67]
Jerling, M.; Huan, B.L.; Leung, K.; Chu, N.; Abdallah, H.; Hussein, Z. Studies to investigate the pharmacokinetic interactions between ranolazine and ketoconazole, diltiazem or simvastatin during combined administration in healthy subjects. J. Clin. Pharmacol., 2005, 45(4), 422-433.
[68]
Herman, B.D.; Fleishaker, J.C.; Brown, M.T. Ketoconazole inhibits the clearance of the enantiomers of the antidepressant reboxetine in humans. Clin. Pharmacol. Ther., 1999, 66(4), 374-389.
[69]
Lahu, G.; Huennemeyer, A.; von Richter, O.; Herrmann, R.; Herzog, R.; Mc Cracken, N.; Zech, K. Effect of single and repeated doses of ketoconazole on the pharmacokinetics of roflumilast and roflumilast N-oxide. J. Clin. Pharmacol., 2008, 48(11), 1339-1349.
[70]
Arlander, E.; Ekström, G.; Alm, C.; Carrillo, J.A.; Bielenstein, M.; Böttiger, Y.; Bertilsson, L.; Gustafsson, L.L. Metabolism of ropivacaine in humans is mediated by CYP1A2 and to a minor extent by CYP3A4: An interaction study with fluvoxamine and ketoconazole as in vivo inhibitors. Clin. Pharmacol. Ther., 1998, 64(5), 484-491.
[71]
Shi, J.G.; Chen, X.; Emm, T.; Scherle, P.A.; McGee, R.F.; Lo, Y.; Landman, R.R.; McKeever, E.G.; Punwani, N.G.; Williams, W.V.; Yeleswaram, S. The effect of CYP3A4 inhibition or induction on the pharmacokinetics and pharmacodynamics of orally administered ruxolitinib (INCB018424phosphate) in healthy volunteers. J. Clin. Pharmacol., 2012, 52(6), 809-818.
[72]
Kantola, T.; Kivistö, K.T.; Neuvonen, P.J. Erythromycin and verapamil considerably increase serum simvastatin and simvastatin acid concentrations. Clin. Pharmacol. Ther., 1998, 64(2), 177-182.
[73]
Kaplan, B.; Kriesche, H-U.M.; Napoli, K.L.; Kahan, B.D. The effects of relative timing of sirolimus and cyclosporine microemulsion formulation coadministration on the pharmacokinetics of each agent. Clin. Pharmacol. Ther., 1998, 63(1), 48-53.
[74]
Kovarik, J.M.; Huang, H-L.A.; Slade, A.; Sfikas, N.; Chandler, P.A. The effect on sotrastaurin pharmacokinetics of strong CYP3A inhibition by ketoconazole. Br. J. Clin. Pharmacol., 2009, 68(3), 381-385.
[75]
Floren, L.C.; Bekersky, I.; Benet, L.Z.; Mekki, Q.; Dressler, D.; Lee, J.W.; Roberts, J.P.; Hebert, M.F. Tacrolimus oral bioavailability doubles with co-administration of ketoconazole. Clin. Pharmacol. Ther., 1997, 62(1), 41-49.
[76]
Honig, P.K.; Wortham, D.C.; Zamani, K.; Mullin, J.C.; Conner, D.P.; Cantilena, L.R. The effect of fluconazole on the steady‐state pharmacokinetics and electrocardiographic pharmacodynamics of terfenadine in humans. Clin. Pharmacol. Ther., 1993, 53, 630-636.
[77]
Stern, R.H.; Smithers, J.A.; Olson, S.C. Atorvastatin does not produce a clinically significant effect on the pharmacokinetics of terfenadine. J. Clin. Pharmacol., 1998, 38(8), 753-757.
[78]
Shoaf, S.E.; Bricmont, P.; Mallikaarjun, S. Effects of CYP3A4 inhibition and induction on the pharmacokinetics and pharmacodynamics of tolvaptan, a non-peptide AVP antagonist in healthy subjects. Br. J. Clin. Pharmacol., 2012, 73(4), 579-587.
[79]
Farkas, D.; Volak, L.P.; Harmatz, J.S.; von Moltke, L.L.; Court, M.H.; Greenblatt, D.J. Short-term clarithromycin administration impairs clearance and enhances pharmacodynamic effects of trazodone but not of zolpidem. Clin. Pharmacol. Ther., 2009, 85(6), 644-650.
[80]
Greenblatt, D.J.; von Moltke, L.L.; Harmatz, J.S.; Fogelman, S.M.; Chen, G.; Graf, J.A.; Mertzanis, P.; Byron, S.; Culm, K.E.; Granda, B.W.; Daily, J.P.; Shader, R.I. Short-term exposure to low-dose ritonavir impairs clearance and enhances adverse effects of trazodone. J. Clin. Pharmacol., 2003, 43(4), 414-422.
[81]
Greenblatt, D.J.; Von Moltke, L.L.; Harmatz, J.S.; Counihan, M.; Graf, J.A.; Durol, A.L.; Mertzanis, P.; Duan, S.X.; Wright, C.E.; Shader, R.I. Inhibition of triazolam clearance by macrolide antimicrobial agents: In vitro correlates and dynamic consequences. Clin. Pharmacol. Ther., 1998, 64(3), 278-285.
[82]
Neuvonen, P.J.; Varhe, A.; Olkkola, K.T. The effect of ingestion time interval on the interaction between itraconazole and triazolam. Clin. Pharmacol. Ther., 1996, 60, 326-331.
[83]
Varhe, A.; Olkkola, K.T.; Neuvonen, P.J. Diltiazem enhances the effects of triazolam by inhibiting its metabolism. Clin. Pharmacol. Ther., 1996, 59(4), 369-375.
[84]
Varhe, A.; Olkkola, K.T.; Neuvonen, P.J. Oral triazolam is potentially hazardous to patients receiving systemic antimycotics ketoconazole or itraconazole. Clin. Pharmacol. Ther., 1994, 56(6), 601-607.
[85]
Varhe, A.; Olkkola, K.T.; Neuvonen, P.J. Effect of fluconazole dose on the extent of fluconazole‐triazolam interaction. Br. J. Clin. Pharmacol., 1996, 42(4), 465-470.
[86]
Backman, J.T.; Wang, J-S.; Xia, Wen. X.; Kivistö, K.T.; Neuvonen, P.J. Mibefradil but not isradipine substantially elevates the plasma concentrations of the CYP3A4 substrate Triazolam. Clin. Pharmacol. Ther., 1999, 66(4), 401-407.
[87]
Miceli, J.J.; Smith, M.; Robarge, L.; Morse, T.; Laurent, A. The effects of ketoconazole on ziprasidone pharmacokinetics Ð a placebo-controlled crossover study in healthy volunteers. Br. J. Clin. Pharmacol., 2000, 49(Suppl. 1), 71S-76S.
[88]
Greenblatt, D.J.; Von Moltke, L.L.; Harmatz, J.S.; Mertzanis, P.; Graf, J.A.; Durol, A.L.; Counihan, M.; Roth-Schechter, B.; Shader, R.I. Kinetic and dynamic interaction study of zolpidem with ketoconazole, itraconazole, and fluconazole. Clin. Pharmacol. Ther., 1998, 64(6), 661-671.
[89]
Kivistö, K.T.; Lamberg, T.S.; Kantola, T.; Neuvonen, P.J. Plasma buspirone concentrations are greatly increased by erythromycin and itraconazole. Clin. Pharmacol. Ther., 1997, 62, 348-354.
[90]
Ouellet, D.; Bramson, C.; Roman, D.; Remmers, A.E.; Randinitis, E.; Milton, A.; Gardner, M. Effects of three cytochrome P450 inhibitors, ketoconazole, fluconazole, and paroxetine, on the pharmacokinetics of lasofoxifene. Br. J. Clin. Pharmacol., 2007, 63(1), 59-66.
[91]
Backman, J.T.; Olkkola, K.T.; Aranko, K.; Himberg, J.J.; Neuvonen, P.J. Dose of midazolam should be reduced during diltiazem and verapamil treatments. Br. J. Clin. Pharmacol., 1994, 37(3), 221-225.
[92]
Rebello, S.; Leon, S.; Hariry, S.; Dahlke, M.; Jarugula, V. Effect of verapamil on the pharmacokinetics of aliskiren in healthy participants. J. Clin. Pharmacol., 2011, 51, 218-228.
[93]
Greenblatt, D.J.; Wright, C.E.; Von Moltke, L.L.; Harmatz, J.S.; Ehrenberg, B.L.; Harrel, L.M.; Corbett, K.; Counihan, M.; Tobias, S.; Shader, R.I. Ketoconazole inhibition of triazolam and alprazolam clearance: Differential kinetic and dynamic consequences. Clin. Pharmacol. Ther., 1998, 64, 237-247.
[94]
Yasui, N.; Otani, K.; Kaneko, S.; Ohkubo, T.; Osanai, T.; Sugawara, K.; Chiba, K.; Ishizaki, T. A kinetic and dynamic study of oral alprazolam with and without erythromycin in humans: In vivo evidence for the involvement of CYP3A4 in alprazolam metabolism. Clin. Pharmacol. Ther., 1996, 59, 514-519.
[95]
Richards, D.B.; Walker, G.A.; Mandagere, A.; Magee, M.H.; Henderson, L.S. Effect of ketoconazole on the pharmacokinetic profile of ambrisentan. J. Clin. Pharmacol., 2009, 49, 719-724.
[96]
Ando, H.; Tsuruoka, S.; Yanagihara, H.; Sugimoto, K.I.; Miyata, M.; Yamazoe, Y.; Takamura, T.; Kaneko, S.; Fujimura, A. Effects of grapefruit juice on the pharmacokinetics of pitavastatin and atorvastatin. Br. J. Clin. Pharmacol., 2005, 60, 494-497.
[97]
Abbas, R.; Hug, B.A.; Leister, C.; Burns, J.; Sonnichsen, D. Effect of ketoconazole on the pharmacokinetics of oral bosutinib in healthy subjects. J. Clin. Pharmacol., 2011, 51, 1721-1727.
[98]
van Giersbergen, P.L.M.; Halabi, A.; Dingemanse, J. Single- and multiple-dose pharmacokinetics of bosentan and its interaction with ketoconazole. Br. J. Clin. Pharmacol., 2002, 53, 589-595.
[99]
Ohtani, Y.; Kotegawa, T.; Tsutsumi, K.; Morimoto, T.; Hirose, Y.; Nakano, S. Effect of fluconazole on the pharmacokinetics and pharmacodynamics of oral and rectal bromazepam: An application of electroencephalography as the pharmacodynamic method. J. Clin. Pharmacol., 2002, 42, 183-191.
[100]
Osanai, T.; Ohkubo, T.; Yasui, N.; Kondo, T.; Kaneko, S. Effect of itraconazole on the pharmacokinetics and pharmacodynamics of a single oral dose of brotizolam. Br. J. Clin. Pharmacol., 2004, 58, 476-481.
[101]
Dilger, K.; Fux, R.; Röck, D.; Mörike, K.; Gleiter, C.H. Effect of high-dose metronidazole on pharmacokinetics of oral budesonide and vice versa: A double drug interaction study. J. Clin. Pharmacol., 2007, 47, 1532-1539.
[102]
Seidegård, J. Reduction of the inhibitory effect of ketoconazole on budesonide pharmacokinetics by separation of their time of administration. Clin. Pharmacol. Ther., 2000, 68, 13-17.
[103]
Yoshizato, T.; Kotegawa, T.; Imai, H.; Tsutsumi, K.; Imanaga, J.; Ohyama, T.; Ohashi, K. Itraconazole and domperidone: A placebo-controlled drug interaction study. Eur. J. Clin. Pharmacol., 2012, 68, 1287-1284.
[104]
Chaikin, P.; Gillen, M.S.; Malik, M.; Pentikis, H.; Rhodes, G.R.; Roberts, D.J. Co-administration of ketoconazole with H1-antagonists ebastine and loratadine in healthy subjects: pharmacokinetic and pharmacodynamic effects. Br. J. Clin. Pharmacol., 2005, 59(3), 346-354.
[105]
Rakhit, A.; Pantze, M.P.; Fettner, S.; Jones, H.M.; Charoin, J.E.; Riek, M.; Lum, B.L.; Hamilton, M. The effects of CYP3A4 inhibition on erlotinib pharmacokinetics: Computer-based simulation (SimCYP™) predicts in vivo metabolic inhibition. Eur. J. Clin. Pharmacol., 2008, 64(1), 31-41.
[106]
Agrawal, N.G.B.; Miller, J.L.; Schultz, A.; Gottlieb, A.B.; Kraft, W.K.; Greenberg, H.E.; Waldman, S.A.; Curtis, S.P.; Gottesdiener, K.M. The effects of modifying in vivo cytochrome P450 3A (CYP3A) activity on etoricoxib pharmacokinetics and of etoricoxib administration on CYP3A activity. J. Clin. Pharmacol., 2004, 44(10), 1125-1131.
[107]
Bailey, D.G.; Bend, J.R.; Malcolm, O.; Arnold, J.; Spence, J.D. Erythromycin-felodipine interaction: Magnitude, mechanism, and comparison with grapefruit juice. Clin. Pharmacol. Ther., 1996, 60(1), 25-33.
[108]
Malhotra, B.; Sachse, R.; Wood, N. Evaluation of drug-drug interactions with fesoterodine. Eur. J. Clin. Pharmacol., 2009, 65(6), 551-560.
[109]
Kim, J.W.; Yi, S.; Kim, T.E.; Lim, K.S.; Yoon, S.H.; Cho, J.Y.; Lee, M.G.; Song, I.S.; Shin, S.G.; Jang, I.J.; Yu, K.S. Increased systemic exposure of fimasartan, an angiotensin II receptor antagonist, by ketoconazole and rifampicin. J. Clin. Pharmacol., 2013, 53(1), 75-81.
[110]
Spina, E.; Avenoso, A.; Campo, G.M.; Scordo, M.G.; Caputi, A.P.; Perucca, E. Effect of ketoconazole on the pharmacokinetics of imipramine and desipramine in healthy subjects. Br. J. Clin. Pharmacol., 1997, 43, 315-318.
[111]
Langdon, G.; Davis, J.; Layton, G.; Chong, C-L.; Weissgerber, G.; Vourvahis, M. Effects of ketoconazole and valproic acid on the pharmacokinetics of the next generation NNRTI, lersivirine (UK-453,061), in healthy adult subjects. Br. J. Clin. Pharmacol., 2011, 5, 768-775.
[112]
Brannan, M.D.; Reidenberg, P.; Radwanski, E.; Shneyer, L.; Lin, C.C.; Cayen, M.N.; Affrime, M.B. Loratadine administered concomitantly with erythromycin: Pharmacokinetic and electrocardiographic evaluations. Clin. Pharmacol. Ther., 1995, 58(3), 269-278.
[113]
Kosoglou, T.; Salfi, M.; Lim, J.M.; Batra, V.K.; Cayen, M.N.; Affrime, M.B. Evaluation of the pharmacokinetics and electrocardiographic pharmacodynamics of loratadine with concomitant administration of ketoconazole or cimetidine. Br. J. Clin. Pharmacol., 2000, 50(6), 581-589.
[114]
Kazierad, D.J.; Martin, D.E.; Blum, R.A.; Tenero, D.M.; Ilson, B.; Boike, S.C.; Etheredge, R.; Jorkasky, D.K. Effect of fluconazole on the pharmacokinetics of eprosartan and losartan in healthy male volunteers. Clin. Pharmacol. Ther., 1997, 62(4), 417-425.
[115]
Lebrun‐Vignes, B.; Archer, V.C.; Diquet, B.; Levron, J.C.; Chosidow, O.; Puech, A.J.; Warot, D. Effect of itraconazole on the pharmacokinetics of prednisolone and methylprednisolone and cortisol secretion in healthy subjects. Br. J. Clin. Pharmacol., 2001, 51(5), 443-450.
[116]
Majumdar, A.K.; McCrea, J.B.; Panebianco, D.L.; Hesney, M.; Dru, J.; Constanzer, M.; Goldberg, M.R.; Gottesdiener, K.M.; Lines, C.R. Effects of aprepitant on cytochrome P450 3A4 activity using midazolam as a probe. Clin. Pharmacol. Ther., 2003, 74, 150-156.
[117]
Mueck, W.; Kubitza, D.; Becka, M. Co‐administration of rivaroxaban with drugs that share its elimination pathways: Pharmacokinetic effects in healthy subjects. Br. J. Clin. Pharmacol., 2013, 76(3), 455-466.
[118]
Nassr, N.; Lahu, G.; Von Richter, O.; Reutter, F.; Knoerzer, D.; Zech, K.; Erb, K.A.; Schug, B.; Blume, H.; Hermann, R. Lack of a pharmacokinetic interaction between steady‐state roflumilast and single‐dose midazolam in healthy subjects. Br. J. Clin. Pharmacol., 2006, 63(3), 365-370.
[119]
Saari, T.I.; Laine, K.; Leino, K.; Valtonen, M.; Neuvonen, P.J.; Olkkola, K.T. Effect of voriconazole on the pharmacokinetics and pharmacodynamics of intravenous and oral midazolam. Clin. Pharmacol. Ther., 2006, 79, 362-370.
[120]
Veronese, M.L.; Gillen, L.P.; Dorval, E.P.; Hauck, W.W.; Waldman, S.A.; Greenberg, H.E. Effect of mibefradil on CYP3A4 in vivo. J. Clin. Pharmacol., 2003, 43(10), 1091-1100.
[121]
Jing‐He, Yan J.-H.; Marino, M.R; Smith, R.A.; Kanamaluru, V.; O’Mara, E.M.; Grasela, D.M. The Effect of ravuconazole on the pharmacokinetics of nelfinavir in healthy male volunteers. J. Clin. Pharmacol., 2006, 46(2), 193-200.
[122]
Heinig, R.; Adelmann, H.G.; Ahr, G. The effect of ketoconazole on the pharmacokinetics, pharmacodynamics and safety of nisoldipine. Eur. J. Clin. Pharmacol., 1999, 55(1), 57-60.
[123]
Kotsuma, M.; Tokui, T.; Freudenthaler, S.; Nishimura, K. Effects of ketoconazole and quinidine on pharmacokinetics of pactimibe and its plasma metabolite, R-125528, in humans. Drug Metab. Dispos., 2008, 36(8), 1505-1511.
[124]
Grimm, S.W.; Richtand, N.M.; Winter, H.R.; Stams, K.R.; Reele, S.B. Effects of cytochrome P450 3A modulators ketoconazole and carbamazepine on quetiapine pharmacokinetics. Br. J. Clin. Pharmacol., 2005, 61(1), 58-69.
[125]
Laganière, S.; Davies, R.F.; Carignan, G.; Foris, K.; Goernert, L.; Carrier, K.; Pereira, C.; McGilveray, I. Pharmacokinetic and pharmacodynamic interactions between diltiazem and quinidine. Clin. Pharmacol. Ther., 1996, 60(3), 255-264.
[126]
Hatorp, V.; Hansen, K.T.; Thomsen, M.S. Influence of drugs interacting with CYP3A4 on the pharmacokinetics, pharmacodynamics, and safety of the prandial glucose regulator repaglinide. J. Clin. Pharmacol., 2003, 43(6), 649-660.
[127]
Kajosaari, L.I.; Niemi, M.; Neuvonen, M.; Laitila, J.; Neuvonen, P.J.; Backman, J.T. Cyclosporine markedly raises the plasma concentrations of repaglinide. Clin. Pharmacol. Ther., 2005, 78(4), 388-399.
[128]
Mueck, W.; Kubitza, D.; Becka, M. Co‐administration of rivaroxaban with drugs that share its elimination pathways: Pharmacokinetic effects in healthy subjects. Br. J. Clin. Pharmacol., 2013, 76(3), 455-466.
[129]
Park, J-Y.; Kim, K-A.; Shin, J-G.; Young Lee, K. Effect of ketoconazole on the pharmacokinetics of rosiglitazone in healthy subjects. Br. J. Clin. Pharmacol., 2004, 58(4), 397-402.
[130]
Cooper, K.J.; Martin, P.D.; Dane, A.L.; Warwick, M.J.; Raza, A.; Schneck, D.W. Lack of effect of ketoconazole on the pharmacokinetics of rosuvastatin in healthy subjects. Br. J. Clin. Pharmacol., 2003, 55(1), 94-99.
[131]
Cooper, K.J.; Martin, P.D.; Dane, A.L.; Warwick, M.J.; Raza, A.; Schneck, D.W. The effect of erythromycin on the pharmacokinetics of rosuvastatin. Eur. J. Clin. Pharmacol., 2003, 59, 51-56.
[132]
Grub, S.; Bryson, H.; Goggin, T.; Lüdin, E.; Jorga, K. The interaction of saquinavir (soft gelatin capsule) with ketoconazole, erythromycin and rifampicin: Comparison of the effect in healthy volunteers and in HIV-infected patients. Eur. J. Clin. Pharmacol., 2001, 57(2), 115-121.
[133]
Mitra, A.K.; Thummel, K.E.; Kalhorn, T.F.; Kharasch, E.D.; Unadkat, J.D.; Slattery, J.T. Inhibition of sulfamethoxazole hydroxylamine formation by fluconazole in human liver microsomes and healthy volunteers. Clin. Pharmacol. Ther., 1996, 59, 332-340.
[134]
Troost, J.; Tatami, S.; Tsuda, Y.; Mattheus, M.; Mehlburger, L.; Wein, M.; Michel, M.C. Effects of strong CYP2D6 and 3A4 inhibitors, paroxetine and ketoconazole, on the pharmacokinetics and cardiovascular safety of tamsulosin. Br. J. Clin. Pharmacol., 2011, 72(2), 247-256.
[135]
Harris, S.; Hilligoss, D.M.; Colangelo, P.M.; Eller, M.; Okerholm, R. Azithromycin and terfenadine: Lack of drug interaction. Clin. Pharmacol. Ther., 1995, 58, 310-315.
[136]
Rau, S.E.; Bend, J.R.; Arnold, J.M.O.; Tran, L.T.; Spence, J.D.; Bailey, D.G. Grapefruit juice-terfenadine single‐dose interaction: Magnitude, mechanism, and relevance. Clin. Pharmacol. Ther., 1997, 61, 401-409.
[137]
Krishnaiah, Y.S.; Satyanarayana, S.; Visweswaram, D. Interaction between tolbutamide and ketoconazole in healthy subjects. Br. J. Clin. Pharmacol., 1994, 37(2), 205-207.
[138]
Shin, K-H.; Chung, Y-J.; Kim, B-H.; Kim, H-S.; Cho, J-Y.; Jang, I-J.; Shin, S-G.; Yu, K-S. Effect of ketoconazole on the pharmacokinetics of udenafil in healthy Korean subjects. Br. J. Clin. Pharmacol., 2010, 69(3), 307-310.
[139]
Wandel, C.; Lang, C.C.; Cowart, D.C.; Girard, A.F.; Bramer, S.; Flockhart, D.A.; Wood, A.J.J. Effect of CYP3A inhibition on vesnarinone metabolism in humans. Clin. Pharmacol. Ther., 1998, 63, 506-511.
[140]
Garg, A.; Maes, A.; Corr, C.; Jin, B.; Wadhwa, T.; Handa, N.; Van Dyck, K.; De Lepeleire, I.; Shah, J.; Wagner, J.A.; Krishna, R. Effect of diltiazem, a moderate CYP3A inhibitor, on the pharmacokinetics of anacetrapib, a potent cholesteryl ester transfer protein inhibitor, in healthy subjects. J. Clin. Pharmacol., 2011, 51, 436-439.
[141]
Krishna, R.; Bergman, A.J.; Jin, B.; Garg, A.; Roadcap, B.; Chiou, R.; Dru, J.; Cote, J.; Laethem, T.; Wang, R.W.; Didolkar, V.; Vets, E.; Gottesdiener, K.; Wagner, J.A. Assessment of the CYP3A-mediated drug interaction potential of anacetrapib, a potent Cholesteryl Ester Transfer Protein (CETP) inhibitor, in healthy volunteers. J. Clin. Pharmacol., 2009, 49(1), 80-87.
[142]
Lefèvre, G.; Carpenter, P.; Souppart, C.; Schmidli, H.; McClean, M.; Stypinski, D. Pharmacokinetics and electrocardiographic pharmacodynamics of artemether-lumefantrine (Riamet®) with concomitant administration of ketoconazole in healthy subjects. Br. J. Clin. Pharmacol., 2002, 54, 485-492.
[143]
Lam, Y.W.; Alfaro, C.L.; Ereshefsky, L.; Miller, M. Pharmacokinetic and pharmacodynamic interactions of oral midazolam with ketoconazole, fluoxetine, fluvoxamine, and nefazodone. J. Clin. Pharmacol., 2003, 43(11), 1274-1282.
[144]
Wolbold, R.; Klein, K.; Burk, O.; Nussler, A.K.; Neuhaus, P.; Schwab, M.; Zanger, U.M. Sex is a major determinant of CYP3A4 expression in human liver. Hepatology, 2003, 38(4), 978-988.
Related Books
Localized Micro/Nanocarriers for Programmed and On-Demand Controlled Drug Release
Mixed Polymeric Micelles for Osteosarcoma Therapy: Development and Characterization
A Comprehensive Text Book on Self-emulsifying Drug Delivery Systems
Nanomaterials: Evolution and Advancement towards Therapeutic Drug Delivery (Part II)
Nanomaterials: Evolution and Advancement Towards Therapeutic Drug Delivery (Part I)
Article Metrics
51
8
1
1