Gravity influences bevacizumab distribution in an undisturbed balanced salt solution in vitro

Autoři: Rae Young Kim aff001;  Soonil Kwon aff002;  Ho Ra aff001
Působiště autorů: Department of Ophthalmology & Visual Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea aff001;  Department of Ophthalmology, Hallym University Sacred Heart Hospital, Anyang, Republic of Korea aff002
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.pone.0223418



The effects of gravity on bevacizumab or the recommended head position after intraocular bevacizumab injection have not been reported. To evaluate the effect of gravity on bevacizumab in vitro, we added bevacizumab to the upper part of a test tube filled with balanced salt solution (BSS) and examined its distribution over time.

Materials and methods

Sixty-four test tubes were divided equally into two groups; group 1 (32, collected from upper part of the tube) and group 2 (32, collected from lower part of the tube). Each test tube was filled with 5 mL BSS before bevacizumab (1.25 mg/0.05 mL) was added, and then stored at 36°C. Bevacizumab concentration in 8 test tubes from each group was measured at 12, 24, 48, and 168 h using an enzyme-linked immunosorbent analysis (ELISA) kit. Mann–Whitney and Jonckheere–Terpstra tests were used for statistical analysis.


Bevacizumab concentration was significantly higher in Group 2 than in Group 1 at 12, 24, 48, and 168 h (12, 24, 48, and 168 h; P < 0.01 each; Mann–Whitney test). The mean change in bevacizumab concentration over time tended to increase in Group 1 (P < 0.01; Jonckheere–Terpstra test), but tended to decrease in Group 2 (P < 0.01; Jonckheere–Terpstra test).


The significant differences in concentration between the upper and lower parts even after a considerable amount of storage time showed that bevacizumab did not dissolve immediately and diffused evenly throughout the solution. It appeared that more bevacizumab settled in the lower part of the tube than in the upper part because of gravitational force. However, the concentration difference between the upper and lower parts decreased as bevacizumab gradually diffused over time, indicating that the difference in concentration due to gravity was more significant at the beginning of bevacizumab injection.

Klíčová slova:

Drug administration – Enzyme-linked immunoassays – Eyes – Glaucoma – Surgical and invasive medical procedures – Vitrectomy – Gravitation


1. Moss SE, Klein R, Klein BE. The 14-year incidence of visual loss in a diabetic population. Ophthalmology. 1998;105:998–1003. doi: 10.1016/S0161-6420(98)96025-0 9627648

2. Smiddy WE, Flynn HW. Vitrectomy in the management of diabetic retinopathy. Surv Ophthalmol. 1999;43:491–507. doi: 10.1016/s0039-6257(99)00036-3 10416792

3. Cheema RA, Mushtaq J, Al-Khars W, Al-Askar E, Cheema MA. Role of intravitreal bevacizumab (Avastin) injected at the end of diabetic vitrectomy in preventing postoperative recurrent vitreous hemorrhage. Retina. 2010;30:1646–1650. doi: 10.1097/IAE.0b013e3181d6def0 20634777

4. Ferenchak K, Duval R, Cohen JA, MacCumber MW. Intravitreal bevacizumab for postoperative recurrent vitreous hemorrhage after vitrectomy for proliferative diabetic retinopathy. Retina. 2014;34:1177–1181. doi: 10.1097/IAE.0000000000000058 24457977

5. Ahn J, Kim H, Woo SJ, Park JH, Park S, Hwang DJ, et al. Pharmacokinetics of intravitreally injected bevacizumab in vitrectomized eyes. J Ocul Pharmacol Ther. 2013;29:612–618. doi: 10.1089/jop.2013.0009 23735192

6. Xu Y, You Y, Du W, Zhao C, Li J, Mao J, et al. Ocular pharmacokinetics of bevacizumab in vitrectomized eyes with silicone oil tamponade. Invest Ophthalmol Vis Sci. 2012;53:5221–5226. doi: 10.1167/iovs.12-9702 22786911

7. Christoforidis JB, Williams MM, Wang J, Jiang A, Pratt C, Abdel-Rasoul M, et al. Anatomic and pharmacokinetic properties of intravitreal bevacizumab and ranibizumab after vitrectomy and lensectomy. Retina. 2013;33(5):946–952. doi: 10.1097/IAE.0b013e3182753b12 23407351

8. Jooybar E, Abdekhodaie MJ, Farhadi F, Cheng YL. Computational modeling of drug distribution in the posterior segment of the eye: effects of device variables and positions. Math Biosci. 2014;255:11–20. doi: 10.1016/j.mbs.2014.06.008 24946303

9. Lim JI, Anderson CT, Hutchinson A, Buggage RR, Grossniklaus HE. The role of gravity in gentamicin-induced toxic effects in a rabbit model. Arch Ophthalmol. 1994;112:1363–1367. doi: 10.1001/archopht.1994.01090220113032 7945041

10. Jaissle GB, Szurman P, Völker M, Bartz-Schmidt KU. Epiretinal deposit of triamcinolone acetonide at the posterior pole after intravitreal injection. Ophthalmic Surg Lasers Imaging. 2007;38:238–241. 17552392

Článok vyšiel v časopise


2019 Číslo 10