Antitumour activity and plasma; kinetics of bleomycin by continuous and intermittent administration

Y. M. Peng, David S Alberts, H. S G Chen, N. Mason, T. E. Moon

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

We have studied the cytotoxicity of bleomycin (4-10 u/kg/day for 6 days) given by continuous i.p. infusion (using an osmotic minipump) compared to daily i.p. bolus administration, against P388 leukaemic spleen colony-forming-units (LCFU-S). Continuous i.p. bleomycin at 8 u/kg/day caused a 0.5 log greater reduction of LCFU-S than did an identical dose given by intermittent bolus administration. The infusion minipump provided constant bleomycin plasma levels of 0.62±0.03 mu/ml and a total plasma AUC (area under the plasma decay curve) of 89.0 mu.h/ml for 6 days at 8 u/kg/day. Intermittent bolus bleomycin at 8 u./kg/day had a terminal-phase plasma t 1/2 of 15 min and a total 6-day plasma AUC of 90.8mu.h/ml. These pharmacokinetic data validate the osmotic minipump as a constant drug-delivery system, and suggest that the two administration schedules resulted in equal total bleomycin dosages. Although high peak bleomycin plasma levels (i.e. 32 mu/ml) were achieved with the intermittent bolus administration, continuous-infusion bleomycin's greater inhibition of LCFU-S was probably related to the drug's schedule-dependent cell-killing characteristics. The results of this study provide further rationale for the continuing use of infusion bleomycin schedules in cancer patients.

Original languageEnglish (US)
Pages (from-to)644-647
Number of pages4
JournalBritish Journal of Cancer
Volume41
Issue number4
DOIs
StatePublished - 1980

Fingerprint

Bleomycin
Appointments and Schedules
Area Under Curve
Drug Delivery Systems
Stem Cells
Spleen
Pharmacokinetics
Pharmaceutical Preparations
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Antitumour activity and plasma; kinetics of bleomycin by continuous and intermittent administration. / Peng, Y. M.; Alberts, David S; Chen, H. S G; Mason, N.; Moon, T. E.

In: British Journal of Cancer, Vol. 41, No. 4, 1980, p. 644-647.

Research output: Contribution to journalArticle

Peng, Y. M. ; Alberts, David S ; Chen, H. S G ; Mason, N. ; Moon, T. E. / Antitumour activity and plasma; kinetics of bleomycin by continuous and intermittent administration. In: British Journal of Cancer. 1980 ; Vol. 41, No. 4. pp. 644-647.
@article{50d5c11273664f4dbadb2b132aa57594,
title = "Antitumour activity and plasma; kinetics of bleomycin by continuous and intermittent administration",
abstract = "We have studied the cytotoxicity of bleomycin (4-10 u/kg/day for 6 days) given by continuous i.p. infusion (using an osmotic minipump) compared to daily i.p. bolus administration, against P388 leukaemic spleen colony-forming-units (LCFU-S). Continuous i.p. bleomycin at 8 u/kg/day caused a 0.5 log greater reduction of LCFU-S than did an identical dose given by intermittent bolus administration. The infusion minipump provided constant bleomycin plasma levels of 0.62±0.03 mu/ml and a total plasma AUC (area under the plasma decay curve) of 89.0 mu.h/ml for 6 days at 8 u/kg/day. Intermittent bolus bleomycin at 8 u./kg/day had a terminal-phase plasma t 1/2 of 15 min and a total 6-day plasma AUC of 90.8mu.h/ml. These pharmacokinetic data validate the osmotic minipump as a constant drug-delivery system, and suggest that the two administration schedules resulted in equal total bleomycin dosages. Although high peak bleomycin plasma levels (i.e. 32 mu/ml) were achieved with the intermittent bolus administration, continuous-infusion bleomycin's greater inhibition of LCFU-S was probably related to the drug's schedule-dependent cell-killing characteristics. The results of this study provide further rationale for the continuing use of infusion bleomycin schedules in cancer patients.",
author = "Peng, {Y. M.} and Alberts, {David S} and Chen, {H. S G} and N. Mason and Moon, {T. E.}",
year = "1980",
doi = "10.1038/bjc.1980.110",
language = "English (US)",
volume = "41",
pages = "644--647",
journal = "British Journal of Cancer",
issn = "0007-0920",
publisher = "Nature Publishing Group",
number = "4",

}

TY - JOUR

T1 - Antitumour activity and plasma; kinetics of bleomycin by continuous and intermittent administration

AU - Peng, Y. M.

AU - Alberts, David S

AU - Chen, H. S G

AU - Mason, N.

AU - Moon, T. E.

PY - 1980

Y1 - 1980

N2 - We have studied the cytotoxicity of bleomycin (4-10 u/kg/day for 6 days) given by continuous i.p. infusion (using an osmotic minipump) compared to daily i.p. bolus administration, against P388 leukaemic spleen colony-forming-units (LCFU-S). Continuous i.p. bleomycin at 8 u/kg/day caused a 0.5 log greater reduction of LCFU-S than did an identical dose given by intermittent bolus administration. The infusion minipump provided constant bleomycin plasma levels of 0.62±0.03 mu/ml and a total plasma AUC (area under the plasma decay curve) of 89.0 mu.h/ml for 6 days at 8 u/kg/day. Intermittent bolus bleomycin at 8 u./kg/day had a terminal-phase plasma t 1/2 of 15 min and a total 6-day plasma AUC of 90.8mu.h/ml. These pharmacokinetic data validate the osmotic minipump as a constant drug-delivery system, and suggest that the two administration schedules resulted in equal total bleomycin dosages. Although high peak bleomycin plasma levels (i.e. 32 mu/ml) were achieved with the intermittent bolus administration, continuous-infusion bleomycin's greater inhibition of LCFU-S was probably related to the drug's schedule-dependent cell-killing characteristics. The results of this study provide further rationale for the continuing use of infusion bleomycin schedules in cancer patients.

AB - We have studied the cytotoxicity of bleomycin (4-10 u/kg/day for 6 days) given by continuous i.p. infusion (using an osmotic minipump) compared to daily i.p. bolus administration, against P388 leukaemic spleen colony-forming-units (LCFU-S). Continuous i.p. bleomycin at 8 u/kg/day caused a 0.5 log greater reduction of LCFU-S than did an identical dose given by intermittent bolus administration. The infusion minipump provided constant bleomycin plasma levels of 0.62±0.03 mu/ml and a total plasma AUC (area under the plasma decay curve) of 89.0 mu.h/ml for 6 days at 8 u/kg/day. Intermittent bolus bleomycin at 8 u./kg/day had a terminal-phase plasma t 1/2 of 15 min and a total 6-day plasma AUC of 90.8mu.h/ml. These pharmacokinetic data validate the osmotic minipump as a constant drug-delivery system, and suggest that the two administration schedules resulted in equal total bleomycin dosages. Although high peak bleomycin plasma levels (i.e. 32 mu/ml) were achieved with the intermittent bolus administration, continuous-infusion bleomycin's greater inhibition of LCFU-S was probably related to the drug's schedule-dependent cell-killing characteristics. The results of this study provide further rationale for the continuing use of infusion bleomycin schedules in cancer patients.

UR - http://www.scopus.com/inward/record.url?scp=0018856696&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0018856696&partnerID=8YFLogxK

U2 - 10.1038/bjc.1980.110

DO - 10.1038/bjc.1980.110

M3 - Article

VL - 41

SP - 644

EP - 647

JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

IS - 4

ER -