Pharmacokinetics of bleomycin sclerotherapy in patients with vascular malformations

Pediatr Blood Cancer. 2022 Aug;69(8):e29733. doi: 10.1002/pbc.29733. Epub 2022 Apr 28.

Abstract

Bleomycin, a chemotherapy agent that inhibits synthesis of DNA, has been increasingly utilized in sclerotherapy for patients with vascular malformations. A serious long-term risk of intravenous bleomycin is dose-dependent interstitial pneumonitis. Little is known about absorption and circulating levels of bleomycin when used in sclerotherapy for patients with vascular malformations. This is an Institutional Review Board (IRB)-approved prospective study on patients receiving bleomycin sclerotherapy in the management of vascular malformations. Depending on the type of vascular malformation, bleomycin was administered either in the lumen or interstitial space of the involved lesion. A bleomycin assay measured serum bleomycin plasma concentrations versus time at seven intervals following treatment. Pharmacokinetic parameters were obtained for each participant and included peak plasma concentration (Cmax ), time to reach peak plasma concentration (Tmax ), volume of distribution (Vd ), elimination half-life (t1/2 ), the volume of plasma cleared of the drug per unit time (CL), and total systemic exposure area under the curve (AUC). Fifteen patients were enrolled (5: lymphatic, 4: venous, 6: arteriovenous malformations). Bleomycin was administered interstitially (IS) in 11 patients and intraluminal (IL) in four; median age of 13 years (range: 2-67). Pharmacokinetic analysis revealed terminal elimination half-life (t1/2λz ) of 88.51 (±23.09) and 111.61 (±37.75) minutes for the IS and IL groups, respectively. Vd was 4.86 L (±6.74) and 1.55 L (±0.54) for the IS and IL groups, respectively. AUC was 53.9 (±23.45) and 129.17 (±93.57) mg min/L for the IS and IL groups, respectively. There were no statistically significant differences in t1/2λz , Vd , or AUC parameters between groups. Bleomycin is absorbed systemically when used as a sclerosant for vascular malformations when injected either IS or IL.

Keywords: arteriovenous malformation; bleomycin; lymphatic malformation; pharmacokinetics; vascular anomalies; vascular malformation; venous malformation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Bleomycin
  • Child
  • Child, Preschool
  • Humans
  • Middle Aged
  • Prospective Studies
  • Retrospective Studies
  • Sclerosing Solutions / therapeutic use
  • Sclerotherapy*
  • Treatment Outcome
  • Vascular Malformations* / drug therapy
  • Young Adult

Substances

  • Sclerosing Solutions
  • Bleomycin