Pharmacokinetics and pharmacodynamics of doxorubicin in patients with small cell lung cancer

Stephen C. Piscitelli, Keith A. Rodvold, Daniel A. Rushing, Duane A. Tewksbury

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

The pharmacokinetics and pharmacodynamics of doxorubicin and its metabolite, doxorubicinol, were studied in 35 adult (mean age, 66 1/2 years) patients with small cell lung cancer after a 1-hour intravenous infusion at a dose ranging from 45 to 72 mg/m2. All patients also received concomitant therapy with cyclophosphamide and vincristine. Serum concentrations were sampled to 48 hours after dosing. Wide interpatient variability was observed for all pharmacokinetic parameters with coefficients of variation for apparent volume of distribution, clearance, and area under the curve (AUC) of 62%, 65%, and 65%, respectively. Four patients with impaired liver function showed a significant (p <0.05) decrease in clearance (239 versus 666 ml/min/m2) and increases in AUC (4610 versus 1834 ng·hr/ml) and elimination half-life (49.3 versus 25.6 hours) compared with patients with normal hepatic function. A significant relationship was found between systemic exposure of doxorubicin (defined by AUC) and surviving factor of white blood cells (r = 0.57, p = 0.0025). No relationships were noted between doxorubicinol exposure and surviving factor of white blood cells or platelets. These findings show the important relationship between systemic exposure of doxorubicin and the degree of myelosuppression in patients with small cell lung cancer.

Original languageEnglish (US)
Pages (from-to)555-561
Number of pages7
JournalClinical Pharmacology and Therapeutics
Volume53
Issue number5
StatePublished - May 1993
Externally publishedYes

Fingerprint

Small Cell Lung Carcinoma
Doxorubicin
Pharmacokinetics
Area Under Curve
Leukocytes
Liver
Vincristine
Intravenous Infusions
Cyclophosphamide
Half-Life
Blood Platelets
Serum
adriamycinol

ASJC Scopus subject areas

  • Pharmacology

Cite this

Piscitelli, S. C., Rodvold, K. A., Rushing, D. A., & Tewksbury, D. A. (1993). Pharmacokinetics and pharmacodynamics of doxorubicin in patients with small cell lung cancer. Clinical Pharmacology and Therapeutics, 53(5), 555-561.

Pharmacokinetics and pharmacodynamics of doxorubicin in patients with small cell lung cancer. / Piscitelli, Stephen C.; Rodvold, Keith A.; Rushing, Daniel A.; Tewksbury, Duane A.

In: Clinical Pharmacology and Therapeutics, Vol. 53, No. 5, 05.1993, p. 555-561.

Research output: Contribution to journalArticle

Piscitelli, SC, Rodvold, KA, Rushing, DA & Tewksbury, DA 1993, 'Pharmacokinetics and pharmacodynamics of doxorubicin in patients with small cell lung cancer', Clinical Pharmacology and Therapeutics, vol. 53, no. 5, pp. 555-561.
Piscitelli, Stephen C. ; Rodvold, Keith A. ; Rushing, Daniel A. ; Tewksbury, Duane A. / Pharmacokinetics and pharmacodynamics of doxorubicin in patients with small cell lung cancer. In: Clinical Pharmacology and Therapeutics. 1993 ; Vol. 53, No. 5. pp. 555-561.
@article{5a7e900162cf414cba71aa02da5e8011,
title = "Pharmacokinetics and pharmacodynamics of doxorubicin in patients with small cell lung cancer",
abstract = "The pharmacokinetics and pharmacodynamics of doxorubicin and its metabolite, doxorubicinol, were studied in 35 adult (mean age, 66 1/2 years) patients with small cell lung cancer after a 1-hour intravenous infusion at a dose ranging from 45 to 72 mg/m2. All patients also received concomitant therapy with cyclophosphamide and vincristine. Serum concentrations were sampled to 48 hours after dosing. Wide interpatient variability was observed for all pharmacokinetic parameters with coefficients of variation for apparent volume of distribution, clearance, and area under the curve (AUC) of 62{\%}, 65{\%}, and 65{\%}, respectively. Four patients with impaired liver function showed a significant (p <0.05) decrease in clearance (239 versus 666 ml/min/m2) and increases in AUC (4610 versus 1834 ng·hr/ml) and elimination half-life (49.3 versus 25.6 hours) compared with patients with normal hepatic function. A significant relationship was found between systemic exposure of doxorubicin (defined by AUC) and surviving factor of white blood cells (r = 0.57, p = 0.0025). No relationships were noted between doxorubicinol exposure and surviving factor of white blood cells or platelets. These findings show the important relationship between systemic exposure of doxorubicin and the degree of myelosuppression in patients with small cell lung cancer.",
author = "Piscitelli, {Stephen C.} and Rodvold, {Keith A.} and Rushing, {Daniel A.} and Tewksbury, {Duane A.}",
year = "1993",
month = "5",
language = "English (US)",
volume = "53",
pages = "555--561",
journal = "Clinical Pharmacology and Therapeutics",
issn = "0009-9236",
publisher = "Nature Publishing Group",
number = "5",

}

TY - JOUR

T1 - Pharmacokinetics and pharmacodynamics of doxorubicin in patients with small cell lung cancer

AU - Piscitelli, Stephen C.

AU - Rodvold, Keith A.

AU - Rushing, Daniel A.

AU - Tewksbury, Duane A.

PY - 1993/5

Y1 - 1993/5

N2 - The pharmacokinetics and pharmacodynamics of doxorubicin and its metabolite, doxorubicinol, were studied in 35 adult (mean age, 66 1/2 years) patients with small cell lung cancer after a 1-hour intravenous infusion at a dose ranging from 45 to 72 mg/m2. All patients also received concomitant therapy with cyclophosphamide and vincristine. Serum concentrations were sampled to 48 hours after dosing. Wide interpatient variability was observed for all pharmacokinetic parameters with coefficients of variation for apparent volume of distribution, clearance, and area under the curve (AUC) of 62%, 65%, and 65%, respectively. Four patients with impaired liver function showed a significant (p <0.05) decrease in clearance (239 versus 666 ml/min/m2) and increases in AUC (4610 versus 1834 ng·hr/ml) and elimination half-life (49.3 versus 25.6 hours) compared with patients with normal hepatic function. A significant relationship was found between systemic exposure of doxorubicin (defined by AUC) and surviving factor of white blood cells (r = 0.57, p = 0.0025). No relationships were noted between doxorubicinol exposure and surviving factor of white blood cells or platelets. These findings show the important relationship between systemic exposure of doxorubicin and the degree of myelosuppression in patients with small cell lung cancer.

AB - The pharmacokinetics and pharmacodynamics of doxorubicin and its metabolite, doxorubicinol, were studied in 35 adult (mean age, 66 1/2 years) patients with small cell lung cancer after a 1-hour intravenous infusion at a dose ranging from 45 to 72 mg/m2. All patients also received concomitant therapy with cyclophosphamide and vincristine. Serum concentrations were sampled to 48 hours after dosing. Wide interpatient variability was observed for all pharmacokinetic parameters with coefficients of variation for apparent volume of distribution, clearance, and area under the curve (AUC) of 62%, 65%, and 65%, respectively. Four patients with impaired liver function showed a significant (p <0.05) decrease in clearance (239 versus 666 ml/min/m2) and increases in AUC (4610 versus 1834 ng·hr/ml) and elimination half-life (49.3 versus 25.6 hours) compared with patients with normal hepatic function. A significant relationship was found between systemic exposure of doxorubicin (defined by AUC) and surviving factor of white blood cells (r = 0.57, p = 0.0025). No relationships were noted between doxorubicinol exposure and surviving factor of white blood cells or platelets. These findings show the important relationship between systemic exposure of doxorubicin and the degree of myelosuppression in patients with small cell lung cancer.

UR - http://www.scopus.com/inward/record.url?scp=0027299421&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027299421&partnerID=8YFLogxK

M3 - Article

VL - 53

SP - 555

EP - 561

JO - Clinical Pharmacology and Therapeutics

JF - Clinical Pharmacology and Therapeutics

SN - 0009-9236

IS - 5

ER -