Unexpectedly Low Immunocompetence in Patients on Ketoconazole
T Watanabe, MD, ZH Gao,MD, N Shinozuka,MD, R
Schulick, MD, A Kuo and JF Burdick, MD. Dept. of
Surgery, Johns Hopkins Medical Institutions,
Baltimore, MD
Ketoconazole may be used to decrease the amount
and cost of cyclosporine ("CYA") and tacrolimus
("FK"), but there are few data confirming effectiveness
of this regimen. We compared patients on ketoconazole
and reduced dose CYA or FK using a simplified
immunocompetence assay.
METHODS: The mixed lymphocyte response of blood
mononuclear cells from 171 kidney transplant recipients,
being managed conventionally, and five on ketoconazole,
all doing well, was tested using stimulators either
undepleted ("ND"), or depleted of antigen-presenting
cells ("D"). FK and CYA inhibit the response against
D more effectively than against ND, allowing a gradation
of response scores from 4 (normal responsiveness to both)
through 0.
RESULTS: Normal individuals always have a score of 4.
The average score for the patients managed conventionally
was 2.14, whereas the average for those on ketoconazole
was much lower, 0.88. This resflected a large incidence of
cenventionally-managed patients with no detectable decrement
of immunoresponsiveness (36%), whereas no patient on
ketoconazole had a score above 2 (p<0.001,X^2). This was
strikingly different from the chemical levels, which for those
on ketoconazole were in the low-aceptable range (from 67 to 230).
CONCLUSIONS:
1. Patients using low dose CYA plus ketoconazole to
inhibit metabloism were not under-immunosuppressed, in
spite of relatively low blood levels of the drug.
2. The relatively depressed immunocompetence in the
patients on ketoconazole mandates caution for over
immunosuppression in this setting.
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