Thalidomide pharmacokinetics do not change with chronic administration

S. R. Donahue; J. M. Collins; D. A. Flockhart; D. R. Abernethy; C. B. Trapnell

Thalidomide pharmacokinetics do not change with chronic administration

S. R. Donahue, J. M. Collins, D. A. Flockhart, D. R. Abernethy, C. B. Trapnell

Research output: Contribution to journal › Article › peer-review

Abstract

Thalidomide, an investigationl drug with immunomodulatory as well as teratogenic properties, is currently being evaluated for several clinical uses. Thalidomide-related compounds may be inducers of cytochrome P450 and could alter their own metabolism. Therefore, we evaluated thalidomide pharmacokinetics after initial and chronic dosing. Seven healthy surgically sterilized female subjects aged 21-45 received oral thalidomide 200 mg daily for 21 days. Plasma thalidomide concentrations were determined by HPLC on study days 1 and 21. The calculated pharmacokinetic parameters are summarized below: Study Day AUC (μ·ml^-1-hr) t_1/2 (hr) Cl_oral(1/hr) C_max (μg·ml^-1) t_max (hr) Day 1 33.0 ± 10.1 7.0 ±2.0 6.1 ±1.1 2.9 ±1.0 6.4 ±2.6 Day 21 40.6 ±18.5 7.3 ±2.7 4.9 ±1.5 3.7 ±1.2 5.9 ±3.1 (Values shown are mean±S.D.) In addition, the accumulation ratio (Day 21 AUC_0-24/Day 1 AUC_0→∞) was 1.2 ±0.4. None of the calculated parameters were different as determined by paired t-tests. We conclude that the pharmacokinetics of thalidomide do not change with three weeks of chronic dosing.

Original language	English (US)
Pages (from-to)	236
Number of pages	1
Journal	Clinical pharmacology and therapeutics
Volume	61
Issue number	2
State	Published - 1997
Externally published	Yes

ASJC Scopus subject areas

Pharmacology
Pharmacology (medical)

Cite this

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title = "Thalidomide pharmacokinetics do not change with chronic administration",

abstract = "Thalidomide, an investigationl drug with immunomodulatory as well as teratogenic properties, is currently being evaluated for several clinical uses. Thalidomide-related compounds may be inducers of cytochrome P450 and could alter their own metabolism. Therefore, we evaluated thalidomide pharmacokinetics after initial and chronic dosing. Seven healthy surgically sterilized female subjects aged 21-45 received oral thalidomide 200 mg daily for 21 days. Plasma thalidomide concentrations were determined by HPLC on study days 1 and 21. The calculated pharmacokinetic parameters are summarized below: Study Day AUC (μ·ml-1-hr) t1/2 (hr) Cloral(1/hr) Cmax (μg·ml-1) tmax (hr) Day 1 33.0 ± 10.1 7.0 ±2.0 6.1 ±1.1 2.9 ±1.0 6.4 ±2.6 Day 21 40.6 ±18.5 7.3 ±2.7 4.9 ±1.5 3.7 ±1.2 5.9 ±3.1 (Values shown are mean±S.D.) In addition, the accumulation ratio (Day 21 AUC0-24/Day 1 AUC0→∞) was 1.2 ±0.4. None of the calculated parameters were different as determined by paired t-tests. We conclude that the pharmacokinetics of thalidomide do not change with three weeks of chronic dosing.",

author = "Donahue, {S. R.} and Collins, {J. M.} and Flockhart, {D. A.} and Abernethy, {D. R.} and Trapnell, {C. B.}",

year = "1997",

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T1 - Thalidomide pharmacokinetics do not change with chronic administration

AU - Donahue, S. R.

AU - Collins, J. M.

AU - Flockhart, D. A.

AU - Abernethy, D. R.

AU - Trapnell, C. B.

PY - 1997

Y1 - 1997

N2 - Thalidomide, an investigationl drug with immunomodulatory as well as teratogenic properties, is currently being evaluated for several clinical uses. Thalidomide-related compounds may be inducers of cytochrome P450 and could alter their own metabolism. Therefore, we evaluated thalidomide pharmacokinetics after initial and chronic dosing. Seven healthy surgically sterilized female subjects aged 21-45 received oral thalidomide 200 mg daily for 21 days. Plasma thalidomide concentrations were determined by HPLC on study days 1 and 21. The calculated pharmacokinetic parameters are summarized below: Study Day AUC (μ·ml-1-hr) t1/2 (hr) Cloral(1/hr) Cmax (μg·ml-1) tmax (hr) Day 1 33.0 ± 10.1 7.0 ±2.0 6.1 ±1.1 2.9 ±1.0 6.4 ±2.6 Day 21 40.6 ±18.5 7.3 ±2.7 4.9 ±1.5 3.7 ±1.2 5.9 ±3.1 (Values shown are mean±S.D.) In addition, the accumulation ratio (Day 21 AUC0-24/Day 1 AUC0→∞) was 1.2 ±0.4. None of the calculated parameters were different as determined by paired t-tests. We conclude that the pharmacokinetics of thalidomide do not change with three weeks of chronic dosing.

AB - Thalidomide, an investigationl drug with immunomodulatory as well as teratogenic properties, is currently being evaluated for several clinical uses. Thalidomide-related compounds may be inducers of cytochrome P450 and could alter their own metabolism. Therefore, we evaluated thalidomide pharmacokinetics after initial and chronic dosing. Seven healthy surgically sterilized female subjects aged 21-45 received oral thalidomide 200 mg daily for 21 days. Plasma thalidomide concentrations were determined by HPLC on study days 1 and 21. The calculated pharmacokinetic parameters are summarized below: Study Day AUC (μ·ml-1-hr) t1/2 (hr) Cloral(1/hr) Cmax (μg·ml-1) tmax (hr) Day 1 33.0 ± 10.1 7.0 ±2.0 6.1 ±1.1 2.9 ±1.0 6.4 ±2.6 Day 21 40.6 ±18.5 7.3 ±2.7 4.9 ±1.5 3.7 ±1.2 5.9 ±3.1 (Values shown are mean±S.D.) In addition, the accumulation ratio (Day 21 AUC0-24/Day 1 AUC0→∞) was 1.2 ±0.4. None of the calculated parameters were different as determined by paired t-tests. We conclude that the pharmacokinetics of thalidomide do not change with three weeks of chronic dosing.

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Thalidomide pharmacokinetics do not change with chronic administration

Abstract

ASJC Scopus subject areas

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