Pharmacokinetics of orbital topotecan after ophthalmic artery chemosurgery and intravenous infusion in the swine model Journal Article
| Authors: | Requejo, F.; Opezzo, J.; Vater, A.; Asprea, M.; Lagomarsino, E.; Sampor, C.; Fandiño, A.; Chantada, G.; Francis, J. H.; Abramson, D. H.; Schaiquevich, P. |
| Article Title: | Pharmacokinetics of orbital topotecan after ophthalmic artery chemosurgery and intravenous infusion in the swine model |
| Abstract: | Purpose: Surgery, multiagent systemic chemotherapy, and radiation are used for patients with orbital retinoblastoma but are associated with unacceptable short- and long-term toxicity (including death). We studied orbital and systemic exposure of topotecan in the swine model after ophthalmic artery chemosurgery (OAC) and intravenous (IV) delivery. Methods: Landrace pigs (n = 3) underwent 30-minute OAC of topotecan (4 mg), and samples were serially obtained from the femoral artery and from a microdialysis probe inserted into the lateral rectus muscle sheath of the infused eye as a surrogate of the orbital irrigation. Animals were recovered, and, after a wash-out period, plasma and microdialysate samples from the contralateral eye were collected after a 30-minute IV infusion of topotecan (4 mg). Samples were quantified by high-performance liquid chromatography, and population pharmacokinetic analysis was conducted using MonolixSuite. Results: After OAC, median topotecan exposure in the orbit was 5624 ng × h/mL (range 3922-12531) compared to 23 ng × h/mL (range 18-75) after IV infusion. Thus, topotecan exposure in the orbit was 218-fold (range 75-540) higher after OAC than after IV infusion despite comparable systemic exposure (AUCpl) between routes (AUCpl, OAC: 141 ng × h/mL [127-191] versus AUCpl, IV: 139 ng × h/mL [126-186]). OAC was more selective to target the orbit because the median (range) orbital-to-plasma exposure ratio was 44 (28-65) after OAC compared to 0.18 (0.13-0.40) after IV infusion. Conclusions: OAC of topotecan resulted in higher orbital exposure than after IV infusion and was a more selective route for local drug delivery. Patients with orbital retinoblastoma may benefit from a multimodal treatment strategy including OAC therapy. |
| Keywords: | topotecan; animal; animals; retinoblastoma; retina tumor; retinal neoplasms; ophthalmic artery; infusions, intravenous; swine; intravenous drug administration; pig |
| Journal Title: | Investigative Ophthalmology & Visual Science (IOVS) |
| Volume: | 64 |
| Issue: | 12 |
| ISSN: | 0146-0404 |
| Publisher: | Association for Research in Vision and Ophthalmology |
| Date Published: | 2023-09-01 |
| Start Page: | 3 |
| Language: | English |
| DOI: | 10.1167/iovs.64.12.3 |
| PUBMED: | 37656475 |
| PROVIDER: | scopus |
| PMCID: | PMC10479255 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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