Oral and Topical Treatment of Experimental Herpes Simplex Iritis With Bromovinyldeoxyuridine

A 40-Year Journey in Search of Selective Antiviral Chemotherapy*

“…Inspired by the pioneering work of Herbert Kaufman on the use of idoxuridine (IDU) and trifluridine (TFT) in the topical treatment of HSV keratitis (30) (both compounds are still used for the topical treatment of herpetic eye infections), we described in 1980 in rabbits (31) and shortly thereafter in humans (32) the usefulness of BVDU eye drops (at 0.1%) in the topical treatment of HSV keratitis. BVDU (at 0.1%) proved superior to IDU (0.1%) in the topical treatment of TK: thymidine kinase epithelial HSV-1 keratitis (33), and superior to TFT (1%) in the topical treatment of deep stromal HSV-1 keratitis (34) and uveitis (35). BVDU (0.1% eye drops, at 1-h intervals during the day only) was found effective in the treatment of HSV keratitis where other antiviral drugs (e.g., idoxuridine, trifluridine, vidarabine, or acyclovir) had failed to ameliorate the disease before treatment was switched to BVDU (36).…”

A 40-Year Journey in Search of Selective Antiviral Chemotherapy*

“…Inspired by the pioneering work of Herbert Kaufman on the use of idoxuridine (IDU) and trifluridine (TFT) in the topical treatment of HSV keratitis (30) (both compounds are still used for the topical treatment of herpetic eye infections), we described in 1980 in rabbits (31) and shortly thereafter in humans (32) the usefulness of BVDU eye drops (at 0.1%) in the topical treatment of HSV keratitis. BVDU (at 0.1%) proved superior to IDU (0.1%) in the topical treatment of TK: thymidine kinase epithelial HSV-1 keratitis (33), and superior to TFT (1%) in the topical treatment of deep stromal HSV-1 keratitis (34) and uveitis (35). BVDU (0.1% eye drops, at 1-h intervals during the day only) was found effective in the treatment of HSV keratitis where other antiviral drugs (e.g., idoxuridine, trifluridine, vidarabine, or acyclovir) had failed to ameliorate the disease before treatment was switched to BVDU (36).…”

Untitled

“…Inspired by the pioneering work of Herbert Kaufman on the use of idoxuridine (IDU) and trifluridine (TFT) in the topical treatment of HSV keratitis (30) (both compounds are still used for the topical treatment of herpetic eye infections), we described in 1980 in rabbits (31) and shortly thereafter in humans (32) the usefulness of BVDU eye drops (at 0.1%) in the topical treatment of HSV keratitis. BVDU (at 0.1%) proved superior to IDU (0.1%) in the topical treatment of TK: thymidine kinase epithelial HSV-1 keratitis (33), and superior to TFT (1%) in the topical treatment of deep stromal HSV-1 keratitis (34) and uveitis (35). BVDU (0.1% eye drops, at 1-h intervals during the day only) was found effective in the treatment of HSV keratitis where other antiviral drugs (e.g., idoxuridine, trifluridine, vidarabine, or acyclovir) had failed to ameliorate the disease before treatment was switched to BVDU (36).…”

Selected Milestones in Antiviral Drug Development

“…It was then found that BVDU was much less active against HSV-2 than HSV-1 [ 74 ], and Searle US decided in 1984 not to further pursue the clinical development of BVDU. Attempts to persuade other pharmaceutical companies to pursue the clinical development of the compound invariably failed, although we had reported the efficacy of the compassionate use of BVDU in the systemic treatment of VZV infections (i.e., herpes zoster) [ 75 ] and the topical treatment of HSV eye infections [ 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 ]. Although we were unsuccessful in stimulating any pharmaceutical company into developing BVDU in the Western world, our colleagues in the former DDR were more successful in East Germany and got their BVDU (synthesized locally) marketed by Berlin Chemie for the treatment of herpes zoster in immunosuppressed patients (Helpin ® ).…”

“…infections [76][77][78][79][80][81][82][83][84]. Although we were unsuccessful in stimulating any pharmaceutical company into developing BVDU in the Western world, our colleagues in the former DDR were more successful in East Germany and got their BVDU (synthesized locally) marketed by Berlin Chemie for the treatment of herpes zoster in immunosuppressed patients (Helpin ® ).…”

A 40-Year Journey in Search of Selective Antiviral Chemotherapy*

“…Inspired by the pioneering work of Herbert Kaufman on the use of idoxuridine (IDU) and trifluridine (TFT) in the topical treatment of HSV keratitis (30) (both compounds are still used for the topical treatment of herpetic eye infections), we described in 1980 in rabbits (31) and shortly thereafter in humans (32) the usefulness of BVDU eye drops (at 0.1%) in the topical treatment of HSV keratitis. BVDU (at 0.1%) proved superior to IDU (0.1%) in the topical treatment of TK: thymidine kinase epithelial HSV-1 keratitis (33), and superior to TFT (1%) in the topical treatment of deep stromal HSV-1 keratitis (34) and uveitis (35). BVDU (0.1% eye drops, at 1-h intervals during the day only) was found effective in the treatment of HSV keratitis where other antiviral drugs (e.g., idoxuridine, trifluridine, vidarabine, or acyclovir) had failed to ameliorate the disease before treatment was switched to BVDU (36).…”

Untitled

“…Inspired by the pioneering work of Herbert Kaufman on the use of idoxuridine (IDU) and trifluridine (TFT) in the topical treatment of HSV keratitis (30) (both compounds are still used for the topical treatment of herpetic eye infections), we described in 1980 in rabbits (31) and shortly thereafter in humans (32) the usefulness of BVDU eye drops (at 0.1%) in the topical treatment of HSV keratitis. BVDU (at 0.1%) proved superior to IDU (0.1%) in the topical treatment of TK: thymidine kinase epithelial HSV-1 keratitis (33), and superior to TFT (1%) in the topical treatment of deep stromal HSV-1 keratitis (34) and uveitis (35). BVDU (0.1% eye drops, at 1-h intervals during the day only) was found effective in the treatment of HSV keratitis where other antiviral drugs (e.g., idoxuridine, trifluridine, vidarabine, or acyclovir) had failed to ameliorate the disease before treatment was switched to BVDU (36).…”

Selected Milestones in Antiviral Drug Development

“…It was then found that BVDU was much less active against HSV-2 than HSV-1 [ 74 ], and Searle US decided in 1984 not to further pursue the clinical development of BVDU. Attempts to persuade other pharmaceutical companies to pursue the clinical development of the compound invariably failed, although we had reported the efficacy of the compassionate use of BVDU in the systemic treatment of VZV infections (i.e., herpes zoster) [ 75 ] and the topical treatment of HSV eye infections [ 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 ]. Although we were unsuccessful in stimulating any pharmaceutical company into developing BVDU in the Western world, our colleagues in the former DDR were more successful in East Germany and got their BVDU (synthesized locally) marketed by Berlin Chemie for the treatment of herpes zoster in immunosuppressed patients (Helpin ® ).…”

“…infections [76][77][78][79][80][81][82][83][84]. Although we were unsuccessful in stimulating any pharmaceutical company into developing BVDU in the Western world, our colleagues in the former DDR were more successful in East Germany and got their BVDU (synthesized locally) marketed by Berlin Chemie for the treatment of herpes zoster in immunosuppressed patients (Helpin ® ).…”

A 40-Year Journey in Search of Selective Antiviral Chemotherapy*

“…Inspired by the pioneering work of Herbert Kaufman on the use of idoxuridine (IDU) and trifluridine (TFT) in the topical treatment of HSV keratitis (30) (both compounds are still used for the topical treatment of herpetic eye infections), we described in 1980 in rabbits (31) and shortly thereafter in humans (32) the usefulness of BVDU eye drops (at 0.1%) in the topical treatment of HSV keratitis. BVDU (at 0.1%) proved superior to IDU (0.1%) in the topical treatment of TK: thymidine kinase epithelial HSV-1 keratitis (33), and superior to TFT (1%) in the topical treatment of deep stromal HSV-1 keratitis (34) and uveitis (35). BVDU (0.1% eye drops, at 1-h intervals during the day only) was found effective in the treatment of HSV keratitis where other antiviral drugs (e.g., idoxuridine, trifluridine, vidarabine, or acyclovir) had failed to ameliorate the disease before treatment was switched to BVDU (36).…”

Untitled

“…Inspired by the pioneering work of Herbert Kaufman on the use of idoxuridine (IDU) and trifluridine (TFT) in the topical treatment of HSV keratitis (30) (both compounds are still used for the topical treatment of herpetic eye infections), we described in 1980 in rabbits (31) and shortly thereafter in humans (32) the usefulness of BVDU eye drops (at 0.1%) in the topical treatment of HSV keratitis. BVDU (at 0.1%) proved superior to IDU (0.1%) in the topical treatment of TK: thymidine kinase epithelial HSV-1 keratitis (33), and superior to TFT (1%) in the topical treatment of deep stromal HSV-1 keratitis (34) and uveitis (35). BVDU (0.1% eye drops, at 1-h intervals during the day only) was found effective in the treatment of HSV keratitis where other antiviral drugs (e.g., idoxuridine, trifluridine, vidarabine, or acyclovir) had failed to ameliorate the disease before treatment was switched to BVDU (36).…”

Selected Milestones in Antiviral Drug Development

“…It was then found that BVDU was much less active against HSV-2 than HSV-1 [ 74 ], and Searle US decided in 1984 not to further pursue the clinical development of BVDU. Attempts to persuade other pharmaceutical companies to pursue the clinical development of the compound invariably failed, although we had reported the efficacy of the compassionate use of BVDU in the systemic treatment of VZV infections (i.e., herpes zoster) [ 75 ] and the topical treatment of HSV eye infections [ 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 ]. Although we were unsuccessful in stimulating any pharmaceutical company into developing BVDU in the Western world, our colleagues in the former DDR were more successful in East Germany and got their BVDU (synthesized locally) marketed by Berlin Chemie for the treatment of herpes zoster in immunosuppressed patients (Helpin ® ).…”

“…infections [76][77][78][79][80][81][82][83][84]. Although we were unsuccessful in stimulating any pharmaceutical company into developing BVDU in the Western world, our colleagues in the former DDR were more successful in East Germany and got their BVDU (synthesized locally) marketed by Berlin Chemie for the treatment of herpes zoster in immunosuppressed patients (Helpin ® ).…”