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Pharmacokinetic differences between morning and evening administration of cyclosporine and tacrolimus therapy.

Abstract：

:We performed 24-hour monitoring of cyclosporine (NEO) and tacrolimus (TAC) blood concentrations, evaluating pharmacokinetic parameters and characterizing circadian variations. The monitoring was performed in 10 instances on nine patients administered NEO and 12 out of 11 patients administered TAC. All cases were administered equally divided doses of drugs twice daily orally. Blood samples were taken before and 1, 2, 3, 4, 6, and 12 hours after NEO or TAC administration in the morning and evening. The pharmacokinetic parameters were compared between morning and evening administrations of both drugs. AUC0-12, AUC0-4, C(max), C2, and C(max)/C(min) of NEO and TAC were significantly lower during the evening compared with morning administrations. C(min) values were significantly higher in the evening. T(max) of NEO was longer in evening, although there was not a significant difference; T(max) of TAC was significantly longer in the evening. We found that NEO and TAC administrations in the evening resulted in reduced bioavailability and delayed absorption when compared with drug administrations in the morning. It was thought that the difference in bioavailability between morning and evening administrations was smaller with TAC, because TAC shows lower peak levels and a flatter blood concentration curve than NEO. C(min) was higher after evening administration than morning because of delayed absorption, though the bioavailability of both drugs decreased in the evening. These results suggest that we have to appreciate apparently high trough levels.

journal_name

Transplant Proc

journal_title

Transplantation proceedings

authors

Iwahori T,Takeuchi H,Matsuno N,Johjima Y,Konno O,Nakamura Y,Hama K,Uchiyama M,Ashizawa T,Okuyama K,Nagao T,Abudoshukur M,Hirano T,Oka K

doi

10.1016/j.transproceed.2005.02.104

subject

Has Abstract

pub_date

2005-05-01 00:00:00

pages

1739-40

issue

4

eissn

0041-1345

issn

1873-2623

pii

S0041-1345(05)00220-4

journal_volume

37

pub_type

杂志文章

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