Pharmacokinetics of ifosfamide and its enantiomers following a single 1 h intravenous infusion of the racemate in patients with small cell lung carcinoma

Br J Clin Pharmacol. 1995 Apr;39(4):452-5. doi: 10.1111/j.1365-2125.1995.tb04477.x.

Abstract

Ifosfamide is a chiral pro-drug which is administered clinically in its racemic form. Serum concentrations of rac-ifosfamide and its enantiomers were measured in 12 patients with lung carcinoma following a mean (+/- s.d.) intravenous dose of 4.2 (0.83) g infused over 1 h. The mean (+/- s.d.) volumes of distribution (VSS) of rac, (R)- and (S)-ifosfamide were 0.61 (0.17), 0.60 (0.16) and 0.61 (0.19) l kg-1, respectively. The mean (+/- s.d.) half-lives and clearances were 6.57 (1.69), 7.12 (1.92) and 5.98 (1.52) h and 0.065 (0.013), 0.060 (0.013) and 0.072 (0.014) l h-1 kg-1 for rac, (R)- and (S)-ifosfamide, respectively. The half-life of (S)-ifosfamide was significantly (P < 0.001) shorter than that of (R)-ifosfamide and it had a significantly higher clearance (P < 0.001). There was no significant difference in the volumes of distribution of the enantiomers. The clinical significance of the faster elimination of (S)-ifosfamide is not known.

Publication types

  • Clinical Trial

MeSH terms

  • Aged
  • Carcinoma, Small Cell / drug therapy*
  • Carcinoma, Small Cell / metabolism
  • Female
  • Half-Life
  • Humans
  • Ifosfamide / administration & dosage
  • Ifosfamide / blood
  • Ifosfamide / pharmacokinetics*
  • Ifosfamide / therapeutic use
  • Infusions, Intravenous
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Male
  • Metabolic Clearance Rate
  • Middle Aged
  • Stereoisomerism

Substances

  • Ifosfamide