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The following message was posted to: PharmPK
Dear pharmacologists,
I would know if is it possible drug-interaction
between
Cyclosporin A p.o. and acethylsalicylic acid p.o..
In 2-year old female infant unusual low cyclosporine blood
levels.
Thank in adwance.
Kazimierz H. Kozlowski
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[Two replies - db]
From: Andrew Davey
Date: Thu, 28 Jun 2001 15:42:34 +1200
To: david.-at-.boomer.org
Subject: Re: PharmPK CyA-Salicylate drug interaction
The following message was posted to: PharmPK
Dear Kazimierz
Of the drug interactions reported between cyclosporin and NSAIDS most
involved increased renal toxicity and a rise in cyclosporin levels,
although diclofenac can cause a fall in cyclosporin levels (Stockley I,
Drug interactions, fifth edition). No specific interaction between
acetylsalicylic acid and cylcosporin is noted in Stockley. If your
"interaction" was similar to those reported, a rise in SrCr would be expected.
In the absence of the raised SrCr, one explanation (and this is a long
shot) is that the acute-phase inflammatory response (e.g. following
surgery) can inhibit the metabolism of drugs such as cyclosporin, probably
through the action of IL6 and other cytokines (Chen et al., 1994; Liao and
Reiss, 1996). This effect may be modulated (positively or negatively) by
eicosanoids (Morgan, 1997), the levels of which will, of course, be
influenced by acetylsalicylic acid. If acetylsalicylic acid has prevented
or reversed this enzyme inhibition then the cyclosporin levels may be lower
than normally seen. The regulation of enzymes during inflammation is
complicated and unpredictable, particularly when anti-inflammatory drugs
are used, but this may provide a feasible explanation for unexpected
changes in drug levels.
Chen YL, Le Vraux V, Leneveu A, Dreyfus F, Stheneur A, Florentin I, De
Sousa M, Giroud JP, Flouvat B, Chauvelot-Moachon L. Acute-phase response,
interleukin-6, and alteration of cyclosporine pharmacokinetics. Clinical
Pharmacology & Therapeutics. 1994. 55: 649-60
Liao JS, Reiss WG. Drug-cytokine interactions: focus on cyclosporine.
Pharmacotherapy. 1996. 16: 401-8
Morgan ET. Regulation of cytochromes P450 during inflammation and
infection. Drug Metabolism Reviews. 1997. 29: 1129-88
Regards
Andrew Davey
Dr Andrew Davey
School of Pharmacy
University of Otago
PO Box 913
Dunedin, New Zealand
Ph: (03) 479 7240
Fax (03) 479 7034
---
From: Massimo Baraldo
Date: Thu, 28 Jun 2001 12:53:15 +0200
To: david.-at-.boomer.org
Subject: R: PharmPK CyA-Salicylate drug interaction
The following message was posted to: PharmPK
Dear Kazimierz,
apparently cyclosporine pharmacokinetics is not modify by coadministration
of aspirin. The lack of a pharmacokinetic interaction between cyclosporin
and aspirin has been demonstrated by Kovarik et al."Pharmacokinetics of
Cyclosporine and steady-state aspirin during coadministration" J Clin
Pharmacol 1993; 33: 513-521.
In general, pediatric patients require higher dose of cyclosporine to
achieve target blood concentrations of the drug because the total clearance
of the drug tends to be higher in children than in adults. So younger
patients may be managed more effetively with a 3 time daily administration
schedule rather than twice daily schedule.
Best regards
Massimo Baraldo, MD
Clinical Pharmacologist
Institute of Clinical Pharmacology and Toxicology
School of Medicine
University of Udine
P.le SM Misericordia, 3
33100 Udine
Italy
email: massimo.baraldo.at.dpmsc.uniud.t
URL:http://www.uniud.it/ifct/welcome.html
Phone & Fax: +39 0432 559833
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The following message was posted to: PharmPK
one practical problem in small infants on i.v. cyA may be the absorption of
small dosages to relatively long infusion lines and filters.
We saw these problems by our own. Switching from oral to i.v. resulted in
loss of plasma levels, increasing dosages did not result in increasing
levels.
Did you apply CyA as infusion?
Joachim Boos
Dept. of Pediatric Hematology and Oncology
Munster, Germany
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)