Clinically significant drug interactions with new immunosuppressive agents

被引:82
作者
Mignat, C
机构
[1] Department of Pharmacology, Chrstn. Albrechts University of Kiel, Kiel
[2] Department of Pharmacology, Chrstn. Albrechts University of Kiel, 24105 Kiel
关键词
D O I
10.2165/00002018-199716040-00004
中图分类号
R1 [预防医学、卫生学];
学科分类号
1004 ; 120402 ;
摘要
Tacrolimus (FK506), mycophenolate mofetil, sirolimus (rapamycin), gusperimus, and monoclonal antibody preparations are new immunosuppressive agents, some of which are already approved for clinical use, while others are currently undergoing clinical trials. The present article provides an overview of adverse drug interactions between these immunosuppressants and other drugs which may be used concomitantly. Preliminary data suggest that a pharmacodynamic interaction can occur between tacrolimus and nonsteroidal anti-inflammatory drugs, associated with an increased risk of nephrotoxicity. Erythromycin, clarithromycin, clotrimazole, fluconazole, ketoconazole, and danazol have been shown to increase tacrolimus blood concentrations, while rifampicin (rifampicin) was found to decrease tacrolimus blood concentrations. Evidence from experimental studies suggest that several other drugs also known to affect cytochrome P450 activity may have significant effects on the pharmacokinetics of tacrolimus. On the other hand, tacrolimus itself may inhibit the metabolism of coadministered drugs. This interaction may be attributed to the enhanced renal impairment which has been observed in patients treated with tacrolimus and cyclosporin. The bioavailability of mycophenolic acid, the active metabolite of mycophenolate mofetil, has been reported to be reduced by aluminium/magnesium hydroxide-containing antacids and cholestyramine. Mycophenolic acid, sirolimus and gusperimus may impair bone marrow function and this adverse effect may be enhanced by concomitant administration of other myelosuppressive drugs. There is some evidence that coadministered sirolimus and cyclosporin cause an increase in each other's blood concentrations. An increased risk of central nervous system adverse effects has been described following the combined use of indomethacin and the monoclonal antibody muromonab CD3 (OKT3).
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页码:267 / 278
页数:12
相关论文
共 62 条
[1]   RELEASE OF TUMOR NECROSIS FACTOR, INTERLEUKIN-2, AND GAMMA-INTERFERON IN SERUM AFTER INJECTION OF OKT3 MONOCLONAL-ANTIBODY IN KIDNEY-TRANSPLANT RECIPIENTS [J].
ABRAMOWICZ, D ;
SCHANDENE, L ;
GOLDMAN, M ;
CRUSIAUX, A ;
VEREERSTRAETEN, P ;
DEPAUW, L ;
WYBRAN, J ;
KINNAERT, P ;
DUPONT, E ;
TOUSSAINT, C .
TRANSPLANTATION, 1989, 47 (04) :606-608
[2]  
ALLISON AC, 1993, SPRINGER SEMIN IMMUN, V14, P353
[3]  
ALLISON AC, 1994, IMMUNOSUPPRESSIVE DR, P141
[4]  
AMEMIYA H, 1992, TRANSPLANT P, V24, P1375
[5]   Comparison of acute rapamycin nephrotoxicity with cyclosporine and FK506 [J].
Andoh, TF ;
Burdmann, EA ;
Fransechini, N ;
Houghton, DC ;
Bennett, WM .
KIDNEY INTERNATIONAL, 1996, 50 (04) :1110-1117
[6]  
ASSAN R, 1994, DIABETES METAB, V20, P49
[7]   GRAPEFRUIT JUICE AND DRUGS - HOW SIGNIFICANT IS THE INTERACTION [J].
BAILEY, DG ;
ARNOLD, JMO ;
SPENCE, JD .
CLINICAL PHARMACOKINETICS, 1994, 26 (02) :91-98
[8]   Pharmacokinetics and bioavailability of mycophenolate mofetil in healthy subjects after single-dose oral and intravenous administration [J].
Bullingham, R ;
Monroe, S ;
Nicholls, A ;
Hale, M .
JOURNAL OF CLINICAL PHARMACOLOGY, 1996, 36 (04) :315-324
[9]   Clinically significant drug interactions with cyclosporin - An update [J].
Campana, C ;
Regazzi, MB ;
Buggia, I ;
Molinaro, M .
CLINICAL PHARMACOKINETICS, 1996, 30 (02) :141-179
[10]   PARANOID PSYCHOSIS WITH INDOMETHACIN [J].
CARNEY, MWP .
BRITISH MEDICAL JOURNAL, 1977, 2 (6093) :994-995