Abstract
In a previous study, we noted wide inter-individual variability in drug interactions between voriconazole and tacrolimus, but that analysis did not take into account the routes of administration. In the present study, we analyzed interactions between these two drugs when both agents were administered orally after allogeneic hematopoietic stem cell transplantation (HSCT); the effect of plasma voriconazole levels on the magnitude of the drug interaction was also examined. Twenty-five allogeneic HSCT recipients were evaluated. Trough concentrations of tacrolimus were measured prior to, and periodically for 7-10 days after, initiating voriconazole (400 mg/day) to determine the concentration/dose (C/D) ratio of tacrolimus. The median C/D ratio of tacrolimus increased significantly from 172.8 (range 28.6-1110.7) to 537.5 (range 127.8-1933.3) (ng/mL)/(mg/kg) (P\0.01) following initiation of voriconazole; the median increase was 138.8 % (range -32.0 to 685.7 %). The plasma concentration of voriconazole did not correlate with the increase of the tacrolimus C/D ratio (ρ = 0.16, P = 0.44). These results indicate that oral voriconazole has a significant drug interaction with oral tacrolimus with a wide inter-individual variability, which cannot be explained by the bioavailability of voriconazole. Other possible mechanisms should be explored in future studies.
| Original language | English |
|---|---|
| Pages (from-to) | 564-569 |
| Number of pages | 6 |
| Journal | International Journal of Hematology |
| Volume | 95 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 2012 May |
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Keywords
- Drug interaction
- Hematopoietic stem cell transplantation
- Tacrolimus
- Voriconazole
ASJC Scopus subject areas
- Hematology
Cite this
Drug interaction between voriconazole and tacrolimus and its association with the bioavailability of oral voriconazole in recipients of allogeneic hematopoietic stem cell transplantation. / Mori, Takehiko; Kato, Jun; Yamane, Akiko; Sakurai, Masatoshi; Kohashi, Sumiko; Kikuchi, Taku; Ono, Yukako; Okamoto, Shinichiro.
In: International Journal of Hematology, Vol. 95, No. 5, 05.2012, p. 564-569.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Drug interaction between voriconazole and tacrolimus and its association with the bioavailability of oral voriconazole in recipients of allogeneic hematopoietic stem cell transplantation
AU - Mori, Takehiko
AU - Kato, Jun
AU - Yamane, Akiko
AU - Sakurai, Masatoshi
AU - Kohashi, Sumiko
AU - Kikuchi, Taku
AU - Ono, Yukako
AU - Okamoto, Shinichiro
PY - 2012/5
Y1 - 2012/5
N2 - In a previous study, we noted wide inter-individual variability in drug interactions between voriconazole and tacrolimus, but that analysis did not take into account the routes of administration. In the present study, we analyzed interactions between these two drugs when both agents were administered orally after allogeneic hematopoietic stem cell transplantation (HSCT); the effect of plasma voriconazole levels on the magnitude of the drug interaction was also examined. Twenty-five allogeneic HSCT recipients were evaluated. Trough concentrations of tacrolimus were measured prior to, and periodically for 7-10 days after, initiating voriconazole (400 mg/day) to determine the concentration/dose (C/D) ratio of tacrolimus. The median C/D ratio of tacrolimus increased significantly from 172.8 (range 28.6-1110.7) to 537.5 (range 127.8-1933.3) (ng/mL)/(mg/kg) (P\0.01) following initiation of voriconazole; the median increase was 138.8 % (range -32.0 to 685.7 %). The plasma concentration of voriconazole did not correlate with the increase of the tacrolimus C/D ratio (ρ = 0.16, P = 0.44). These results indicate that oral voriconazole has a significant drug interaction with oral tacrolimus with a wide inter-individual variability, which cannot be explained by the bioavailability of voriconazole. Other possible mechanisms should be explored in future studies.
AB - In a previous study, we noted wide inter-individual variability in drug interactions between voriconazole and tacrolimus, but that analysis did not take into account the routes of administration. In the present study, we analyzed interactions between these two drugs when both agents were administered orally after allogeneic hematopoietic stem cell transplantation (HSCT); the effect of plasma voriconazole levels on the magnitude of the drug interaction was also examined. Twenty-five allogeneic HSCT recipients were evaluated. Trough concentrations of tacrolimus were measured prior to, and periodically for 7-10 days after, initiating voriconazole (400 mg/day) to determine the concentration/dose (C/D) ratio of tacrolimus. The median C/D ratio of tacrolimus increased significantly from 172.8 (range 28.6-1110.7) to 537.5 (range 127.8-1933.3) (ng/mL)/(mg/kg) (P\0.01) following initiation of voriconazole; the median increase was 138.8 % (range -32.0 to 685.7 %). The plasma concentration of voriconazole did not correlate with the increase of the tacrolimus C/D ratio (ρ = 0.16, P = 0.44). These results indicate that oral voriconazole has a significant drug interaction with oral tacrolimus with a wide inter-individual variability, which cannot be explained by the bioavailability of voriconazole. Other possible mechanisms should be explored in future studies.
KW - Drug interaction
KW - Hematopoietic stem cell transplantation
KW - Tacrolimus
KW - Voriconazole
UR - http://www.scopus.com/inward/record.url?scp=84862849999&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84862849999&partnerID=8YFLogxK
U2 - 10.1007/s12185-012-1057-2
DO - 10.1007/s12185-012-1057-2
M3 - Article
C2 - 22461034
AN - SCOPUS:84862849999
VL - 95
SP - 564
EP - 569
JO - International Journal of Hematology
JF - International Journal of Hematology
SN - 0925-5710
IS - 5
ER -