Pharmacokinetics of FK506 in liver transplant recipients after continuous intravenous infusion

A. B. Jain, K. Abu-Elmagd, H. Abdallah, V. Warty, J. Fung, S. Todo, T. E. Starzl, R. Venkataramanan

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Abstract

The first-dose pharmacokinetics of FK506 was studied in nine orthotopic liver transplant patients receiving continuous intravenous infusion of 0.15 mg/kg/day. Multiple blood samples were obtained during the infusion and plasma FK506 concentrations were measured by enzyme-linked immunosorbent assay. The plasma clearance ranged from 0.47 to 5.8 L/minute, and the half- life ranged from 4.5 hours to 33.1 hours. These results indicate the pharmacokinetics of FK506 to be highly variable between patients. FK506 is extensively distributed outside the plasma compartment. FK506 is extensively metabolized in the body, with less than 1% of the administered dose being excreted in the urine as unchanged FK506. The large variability in FK506 kinetics during the immediate postoperative period is attributed to the variability in the functional status of the liver in the transplant patients. Because of the long half-life of FK506, it takes more than 45 hours to reach steady-state concentrations after continuous infusion. Based on the estimated kinetic parameters, it appears that a combination of a bolus or a rapid infusion of .02 mg/kg with a continuous infusion of 0.05 mg/kg/day will provide and maintain a concentration of more than 2 ng/mL from the beginning of the drug treatment.

Original languageEnglish (US)
Pages (from-to)606-611
Number of pages6
JournalJournal of Clinical Pharmacology
Volume33
Issue number7
DOIs
StatePublished - Jan 1 1993

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Tacrolimus
Intravenous Infusions
Pharmacokinetics
Liver
Half-Life
Transplants
Transplant Recipients
Postoperative Period
Enzyme-Linked Immunosorbent Assay
Urine
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

Cite this

Jain, A. B. ; Abu-Elmagd, K. ; Abdallah, H. ; Warty, V. ; Fung, J. ; Todo, S. ; Starzl, T. E. ; Venkataramanan, R. / Pharmacokinetics of FK506 in liver transplant recipients after continuous intravenous infusion. In: Journal of Clinical Pharmacology. 1993 ; Vol. 33, No. 7. pp. 606-611.
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abstract = "The first-dose pharmacokinetics of FK506 was studied in nine orthotopic liver transplant patients receiving continuous intravenous infusion of 0.15 mg/kg/day. Multiple blood samples were obtained during the infusion and plasma FK506 concentrations were measured by enzyme-linked immunosorbent assay. The plasma clearance ranged from 0.47 to 5.8 L/minute, and the half- life ranged from 4.5 hours to 33.1 hours. These results indicate the pharmacokinetics of FK506 to be highly variable between patients. FK506 is extensively distributed outside the plasma compartment. FK506 is extensively metabolized in the body, with less than 1{\%} of the administered dose being excreted in the urine as unchanged FK506. The large variability in FK506 kinetics during the immediate postoperative period is attributed to the variability in the functional status of the liver in the transplant patients. Because of the long half-life of FK506, it takes more than 45 hours to reach steady-state concentrations after continuous infusion. Based on the estimated kinetic parameters, it appears that a combination of a bolus or a rapid infusion of .02 mg/kg with a continuous infusion of 0.05 mg/kg/day will provide and maintain a concentration of more than 2 ng/mL from the beginning of the drug treatment.",
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Jain, AB, Abu-Elmagd, K, Abdallah, H, Warty, V, Fung, J, Todo, S, Starzl, TE & Venkataramanan, R 1993, 'Pharmacokinetics of FK506 in liver transplant recipients after continuous intravenous infusion', Journal of Clinical Pharmacology, vol. 33, no. 7, pp. 606-611. https://doi.org/10.1002/j.1552-4604.1993.tb04712.x

Pharmacokinetics of FK506 in liver transplant recipients after continuous intravenous infusion. / Jain, A. B.; Abu-Elmagd, K.; Abdallah, H.; Warty, V.; Fung, J.; Todo, S.; Starzl, T. E.; Venkataramanan, R.

In: Journal of Clinical Pharmacology, Vol. 33, No. 7, 01.01.1993, p. 606-611.

Research output: Contribution to journalArticle

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T1 - Pharmacokinetics of FK506 in liver transplant recipients after continuous intravenous infusion

AU - Jain, A. B.

AU - Abu-Elmagd, K.

AU - Abdallah, H.

AU - Warty, V.

AU - Fung, J.

AU - Todo, S.

AU - Starzl, T. E.

AU - Venkataramanan, R.

PY - 1993/1/1

Y1 - 1993/1/1

N2 - The first-dose pharmacokinetics of FK506 was studied in nine orthotopic liver transplant patients receiving continuous intravenous infusion of 0.15 mg/kg/day. Multiple blood samples were obtained during the infusion and plasma FK506 concentrations were measured by enzyme-linked immunosorbent assay. The plasma clearance ranged from 0.47 to 5.8 L/minute, and the half- life ranged from 4.5 hours to 33.1 hours. These results indicate the pharmacokinetics of FK506 to be highly variable between patients. FK506 is extensively distributed outside the plasma compartment. FK506 is extensively metabolized in the body, with less than 1% of the administered dose being excreted in the urine as unchanged FK506. The large variability in FK506 kinetics during the immediate postoperative period is attributed to the variability in the functional status of the liver in the transplant patients. Because of the long half-life of FK506, it takes more than 45 hours to reach steady-state concentrations after continuous infusion. Based on the estimated kinetic parameters, it appears that a combination of a bolus or a rapid infusion of .02 mg/kg with a continuous infusion of 0.05 mg/kg/day will provide and maintain a concentration of more than 2 ng/mL from the beginning of the drug treatment.

AB - The first-dose pharmacokinetics of FK506 was studied in nine orthotopic liver transplant patients receiving continuous intravenous infusion of 0.15 mg/kg/day. Multiple blood samples were obtained during the infusion and plasma FK506 concentrations were measured by enzyme-linked immunosorbent assay. The plasma clearance ranged from 0.47 to 5.8 L/minute, and the half- life ranged from 4.5 hours to 33.1 hours. These results indicate the pharmacokinetics of FK506 to be highly variable between patients. FK506 is extensively distributed outside the plasma compartment. FK506 is extensively metabolized in the body, with less than 1% of the administered dose being excreted in the urine as unchanged FK506. The large variability in FK506 kinetics during the immediate postoperative period is attributed to the variability in the functional status of the liver in the transplant patients. Because of the long half-life of FK506, it takes more than 45 hours to reach steady-state concentrations after continuous infusion. Based on the estimated kinetic parameters, it appears that a combination of a bolus or a rapid infusion of .02 mg/kg with a continuous infusion of 0.05 mg/kg/day will provide and maintain a concentration of more than 2 ng/mL from the beginning of the drug treatment.

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