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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
1990-10-1
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pubmed:abstractText |
1. The potential for a drug interaction between cyclosporin A and midazolam was investigated since both compounds appear to be metabolized by the same cytochrome P-450 isoenzyme. 2. In vitro evaluation of the binding of cyclosporin A to rat microsomal cytochrome P-450 indicated a Ks-value of 0.4 microM. In further studies with rat liver microsomes IC50-values of 6, 8 and 70 microM cyclosporin A were determined for the inhibition of the metabolism of midazolam to its alpha-OH-,4-OH- and di-OH-metabolites, respectively. 3. Comparative studies with human liver microsomes indicated IC50-values of approximately 300 microM for the formation of alpha-OH-midazolam and of 65 microM for the formation of 4-OH-midazolam. 4. The pharmacokinetics of a single intravenous dose of midazolam (0.075 mg kg-1) was studied in nine patients receiving cyclosporin A to prevent rejection of their transplanted kidneys. The average steady state blood concentrations of cyclosporin A, measured by r.i.a. using a specific monoclonal antibody, varied during a dosing interval between 175 and 600 ng ml-1. 5. In these patients the hepatic elimination of midazolam was characterized by a mean t1/2 (+/- s.d.) of 2.3 +/- 1.2 h and a plasma clearance (CL) of 414 +/- 95 ml min-1. These values were not different from those of normal human subjects (t1/2 = 1.5 to 4 h, CL = 350 to 700 ml min-1). 6. From the results of the in vitro experiments it is concluded that cyclosporin A may potentially inhibit drug metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/2390433-14209971,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2390433-14907713,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2390433-209288,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2390433-2565211,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2390433-2650953,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2390433-2868869,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2390433-2886317,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2390433-2891494,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2390433-3126014,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2390433-3156545,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2390433-3161005,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2390433-3203485,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2390433-3259880,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2390433-3378384,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2390433-3514043,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2390433-3895660,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2390433-6117393,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2390433-6394264,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2390433-6508804,
http://linkedlifedata.com/resource/pubmed/commentcorrection/2390433-7083724
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0306-5251
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
30
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
71-7
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:2390433-Adult,
pubmed-meshheading:2390433-Animals,
pubmed-meshheading:2390433-Biotransformation,
pubmed-meshheading:2390433-Chromatography, High Pressure Liquid,
pubmed-meshheading:2390433-Cyclosporins,
pubmed-meshheading:2390433-Cytochrome P-450 Enzyme System,
pubmed-meshheading:2390433-Drug Interactions,
pubmed-meshheading:2390433-Female,
pubmed-meshheading:2390433-Humans,
pubmed-meshheading:2390433-Hypnotics and Sedatives,
pubmed-meshheading:2390433-Male,
pubmed-meshheading:2390433-Microsomes, Liver,
pubmed-meshheading:2390433-Midazolam,
pubmed-meshheading:2390433-Middle Aged,
pubmed-meshheading:2390433-Pharmaceutical Preparations,
pubmed-meshheading:2390433-Rats,
pubmed-meshheading:2390433-Rats, Inbred Strains
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pubmed:year |
1990
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pubmed:articleTitle |
Is cyclosporin A an inhibitor of drug metabolism?
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pubmed:affiliation |
Dr Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, FRG.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't
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