Pharmacokinetics of mizoribine in adult living donor liver transplantation

Masahiro Shinoda, M. Tanabe, S. Kawachi, Y. Ono, Tomohisa Hayakawa, O. Iketani, M. Kojima, O. Itano, Hideaki Obara, Minoru Kitago, T. Hibi, Kentaro Matsubara, N. Shimojima, Y. Fuchimoto, K. Hoshino, G. Wakabayashi, M. Shimazu, Yusuke Tanigawara, Tatsuo Kuroda, Y. MorikawaM. Kitajima, Yuukou Kitagawa

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Abstract

We investigated the pharmacokinetics of mizoribine in the acute phase after adult living donor liver transplantation (LDLT). Between February 2004 and October 2009, 16 recipients received immunosuppressive therapy that included mizoribine (100 to 200 mg/d) after undergoing LDLT. We determined the serum levels of mizoribine before (C0) and 3 (C3), 4 (C4), and 10 (C10) hours after administration on postoperative days 3, 7, and 21. We assessed area under the concentration time curve (AUC) (hour · μg/mL), normalized serum concentration (NSC) at C0 [concentration (μg/mL)/dose (mg/kg body weight)], and estimated glomerular filtration rate (eGFR). The mizoribine concentration showed increases at C3 and C4 followed by a decrease at C10 on all days. AUC was 4.3, 5.9, and 8.3 in the 200-mg/d dose group on days 3, 7, and 21, respectively. NSC at C0 increased for 3 weeks after LDLT. There was a significant correlation between the NSC at C0 and eGFR on day 21, but not on days 3 and 7. There were no correlations between the NSC at C0 and either aspartate aminotransferase, total bilirubin, albumin, trough cyclosporine, or trough tacrolimus on any day. The pharmacokinetics of mizoribine in the acute phase after LDLT seems to be affected by postoperative day and renal function.

Original languageEnglish
Pages (from-to)1329-1335
Number of pages7
JournalTransplantation Proceedings
Volume44
Issue number5
DOIs
Publication statusPublished - 2012 Jun

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Living Donors
Liver Transplantation
Pharmacokinetics
Serum
Glomerular Filtration Rate
Area Under Curve
Tacrolimus
Immunosuppressive Agents
Aspartate Aminotransferases
Bilirubin
Cyclosporine
Albumins
Body Weight
bredinin
Kidney

ASJC Scopus subject areas

  • Surgery
  • Transplantation

Cite this

Pharmacokinetics of mizoribine in adult living donor liver transplantation. / Shinoda, Masahiro; Tanabe, M.; Kawachi, S.; Ono, Y.; Hayakawa, Tomohisa; Iketani, O.; Kojima, M.; Itano, O.; Obara, Hideaki; Kitago, Minoru; Hibi, T.; Matsubara, Kentaro; Shimojima, N.; Fuchimoto, Y.; Hoshino, K.; Wakabayashi, G.; Shimazu, M.; Tanigawara, Yusuke; Kuroda, Tatsuo; Morikawa, Y.; Kitajima, M.; Kitagawa, Yuukou.

In: Transplantation Proceedings, Vol. 44, No. 5, 06.2012, p. 1329-1335.

Research output: Contribution to journalArticle

Shinoda, M, Tanabe, M, Kawachi, S, Ono, Y, Hayakawa, T, Iketani, O, Kojima, M, Itano, O, Obara, H, Kitago, M, Hibi, T, Matsubara, K, Shimojima, N, Fuchimoto, Y, Hoshino, K, Wakabayashi, G, Shimazu, M, Tanigawara, Y, Kuroda, T, Morikawa, Y, Kitajima, M & Kitagawa, Y 2012, 'Pharmacokinetics of mizoribine in adult living donor liver transplantation', Transplantation Proceedings, vol. 44, no. 5, pp. 1329-1335. https://doi.org/10.1016/j.transproceed.2012.01.139
Shinoda, Masahiro ; Tanabe, M. ; Kawachi, S. ; Ono, Y. ; Hayakawa, Tomohisa ; Iketani, O. ; Kojima, M. ; Itano, O. ; Obara, Hideaki ; Kitago, Minoru ; Hibi, T. ; Matsubara, Kentaro ; Shimojima, N. ; Fuchimoto, Y. ; Hoshino, K. ; Wakabayashi, G. ; Shimazu, M. ; Tanigawara, Yusuke ; Kuroda, Tatsuo ; Morikawa, Y. ; Kitajima, M. ; Kitagawa, Yuukou. / Pharmacokinetics of mizoribine in adult living donor liver transplantation. In: Transplantation Proceedings. 2012 ; Vol. 44, No. 5. pp. 1329-1335.
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abstract = "We investigated the pharmacokinetics of mizoribine in the acute phase after adult living donor liver transplantation (LDLT). Between February 2004 and October 2009, 16 recipients received immunosuppressive therapy that included mizoribine (100 to 200 mg/d) after undergoing LDLT. We determined the serum levels of mizoribine before (C0) and 3 (C3), 4 (C4), and 10 (C10) hours after administration on postoperative days 3, 7, and 21. We assessed area under the concentration time curve (AUC) (hour · μg/mL), normalized serum concentration (NSC) at C0 [concentration (μg/mL)/dose (mg/kg body weight)], and estimated glomerular filtration rate (eGFR). The mizoribine concentration showed increases at C3 and C4 followed by a decrease at C10 on all days. AUC was 4.3, 5.9, and 8.3 in the 200-mg/d dose group on days 3, 7, and 21, respectively. NSC at C0 increased for 3 weeks after LDLT. There was a significant correlation between the NSC at C0 and eGFR on day 21, but not on days 3 and 7. There were no correlations between the NSC at C0 and either aspartate aminotransferase, total bilirubin, albumin, trough cyclosporine, or trough tacrolimus on any day. The pharmacokinetics of mizoribine in the acute phase after LDLT seems to be affected by postoperative day and renal function.",
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AU - Shinoda, Masahiro

AU - Tanabe, M.

AU - Kawachi, S.

AU - Ono, Y.

AU - Hayakawa, Tomohisa

AU - Iketani, O.

AU - Kojima, M.

AU - Itano, O.

AU - Obara, Hideaki

AU - Kitago, Minoru

AU - Hibi, T.

AU - Matsubara, Kentaro

AU - Shimojima, N.

AU - Fuchimoto, Y.

AU - Hoshino, K.

AU - Wakabayashi, G.

AU - Shimazu, M.

AU - Tanigawara, Yusuke

AU - Kuroda, Tatsuo

AU - Morikawa, Y.

AU - Kitajima, M.

AU - Kitagawa, Yuukou

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N2 - We investigated the pharmacokinetics of mizoribine in the acute phase after adult living donor liver transplantation (LDLT). Between February 2004 and October 2009, 16 recipients received immunosuppressive therapy that included mizoribine (100 to 200 mg/d) after undergoing LDLT. We determined the serum levels of mizoribine before (C0) and 3 (C3), 4 (C4), and 10 (C10) hours after administration on postoperative days 3, 7, and 21. We assessed area under the concentration time curve (AUC) (hour · μg/mL), normalized serum concentration (NSC) at C0 [concentration (μg/mL)/dose (mg/kg body weight)], and estimated glomerular filtration rate (eGFR). The mizoribine concentration showed increases at C3 and C4 followed by a decrease at C10 on all days. AUC was 4.3, 5.9, and 8.3 in the 200-mg/d dose group on days 3, 7, and 21, respectively. NSC at C0 increased for 3 weeks after LDLT. There was a significant correlation between the NSC at C0 and eGFR on day 21, but not on days 3 and 7. There were no correlations between the NSC at C0 and either aspartate aminotransferase, total bilirubin, albumin, trough cyclosporine, or trough tacrolimus on any day. The pharmacokinetics of mizoribine in the acute phase after LDLT seems to be affected by postoperative day and renal function.

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