The erythromycin breath test as a predictor of cyclosporine blood levels.
The daily dose of cyclosporine required to attain a desired blood level can vary greatly among patients. Because elimination of cyclosporine depends on its metabolism in the liver by an enzyme (cytochrome P-450IIIA) that also demethylates erythromycin, we reasoned that the ability of patients to demethylate a test dose of erythromycin might be useful in estimating their appropriate daily doses of cyclosporine. Accordingly, the [14C-N-methyl] erythromycin breath test was administered to 32 patients before they received 3.0, 5.0, or 7.5 mg/kg/day cyclosporine to treat psoriasis. We found that a simple mathematical equation incorporating just the 14CO2 production, the age of the patient, and the daily dose of cyclosporine accounted for almost 80% (R2 = 0.78) of the interpatient variability in cyclosporine blood levels we observed. Our data indicate that P-450IIIA activity largely accounts for the relationship between dose of cyclosporine and blood levels for an individual patient. We conclude that the erythromycin breath test may be a convenient guide for cyclosporine dosing.
Watkins
P B
PB
Department of Medicine, University of Michigan Medical Center, Ann Arbor 48109-0682.
Hamilton
T A
TA
Annesley
T M
TM
Ellis
C N
CN
Kolars
J C
JC
Voorhees
J J
JJ
D000328:Adult; D000368:Aged; D001944:Breath Tests; D002245:Carbon Dioxide / Q000378:metabolism; D003524:Cyclosporins / Q000097:blood* / Q000378:metabolism / Q000627:therapeutic use; D004917:Erythromycin; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D011237:Predictive Value of Tests; D011565:Psoriasis / Q000097:blood / Q000188:drug therapy; D012044:Regression Analysis
D003524:Cyclosporins; D002245:Carbon Dioxide; D004917:Erythromycin