TY - JOUR
T1 - Pharmacokinetics of pars plana intravitreal injections versus microcannula suprachoroidal injections of bevacizumab in a porcine model
AU - Olsen, Timothy W.
AU - Feng, Xiao
AU - Wabner, Kathy
AU - Csaky, Karl
AU - Pambuccian, Stefan
AU - Cameron, John D
PY - 2011/6
Y1 - 2011/6
N2 - Purpose. To compare the pharmacokinetics and tissue response between intravitreal and microcannulation injections into the suprachoroidal space using bevacizumab. Methods. Sixty-two pigs were studied. Either a pars plana intravitreal bevacizumab or a viscoelastic-enhanced microcannula suprachoroidal injection was performed with either 1.25 mg (group 1) or 3 mg (group 2). In group 1, six animals were euthanatized at 0.5, 7, 30, 60, 90, and 120 days after injection (n = 36). In group 2, six animals were euthanatized at 0.5, 7, 14, and 32 days (n = 24). Eyes were enucleated, dissected, and snap-frozen, or they were fixed for histology. Analysis of drug tissue levels was performed at two separate laboratories using masked specimens. Results. Both laboratories were confirmatory. Intravitreal bevacizumab pharmacokinetics demonstrated a gradual decline in tissue levels over 30 to 60 days in both groups 1 and 2. In addition, suprachoroidal bevacizumab tissue levels declined rapidly and were not measurable at or beyond 7 days. Vitreitis and granulomatous vasculitis were noted in 7 of 30 intravitreal injection eyes. Immunohistology suggested a distinctive drug distribution. Conclusions. Direct intravitreal injection of bevacizumab has a more sustained pharmacologic profile than does a similar dose delivered to the suprachoroidal space. Intravitreal injections distributed more to the inner retina, whereas suprachoroidal delivery occurred primarily at the choroid, retinal pigment epithelium, and photoreceptor outer segments. Sustained release formulation of larger biological molecules should be considered to optimize suprachoroidal delivery. Inflammation from injections is granulomatous, seen only with intravitreal injections, and may result from either an altered immune response or a dose-related effect.
AB - Purpose. To compare the pharmacokinetics and tissue response between intravitreal and microcannulation injections into the suprachoroidal space using bevacizumab. Methods. Sixty-two pigs were studied. Either a pars plana intravitreal bevacizumab or a viscoelastic-enhanced microcannula suprachoroidal injection was performed with either 1.25 mg (group 1) or 3 mg (group 2). In group 1, six animals were euthanatized at 0.5, 7, 30, 60, 90, and 120 days after injection (n = 36). In group 2, six animals were euthanatized at 0.5, 7, 14, and 32 days (n = 24). Eyes were enucleated, dissected, and snap-frozen, or they were fixed for histology. Analysis of drug tissue levels was performed at two separate laboratories using masked specimens. Results. Both laboratories were confirmatory. Intravitreal bevacizumab pharmacokinetics demonstrated a gradual decline in tissue levels over 30 to 60 days in both groups 1 and 2. In addition, suprachoroidal bevacizumab tissue levels declined rapidly and were not measurable at or beyond 7 days. Vitreitis and granulomatous vasculitis were noted in 7 of 30 intravitreal injection eyes. Immunohistology suggested a distinctive drug distribution. Conclusions. Direct intravitreal injection of bevacizumab has a more sustained pharmacologic profile than does a similar dose delivered to the suprachoroidal space. Intravitreal injections distributed more to the inner retina, whereas suprachoroidal delivery occurred primarily at the choroid, retinal pigment epithelium, and photoreceptor outer segments. Sustained release formulation of larger biological molecules should be considered to optimize suprachoroidal delivery. Inflammation from injections is granulomatous, seen only with intravitreal injections, and may result from either an altered immune response or a dose-related effect.
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U2 - 10.1167/iovs.10-6291
DO - 10.1167/iovs.10-6291
M3 - Article
C2 - 21447680
AN - SCOPUS:80052385883
SN - 0146-0404
VL - 52
SP - 4749
EP - 4756
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
IS - 7
ER -