Table 4.
Pharmacokinetic parameters of bimatoprost (Bim) and bimatoprost acid (BimA) in aqueous humor after bimatoprost administration through topical or intracameral routes in pre-clinical and clinical studies. Key: NR-Not reported; Cmax- Maximum concentration; Tmax- Time for maximum concentration; AUC- Area under the concentration–time curve; BLQ- below limit of quantitation;
| Route (frequency and duration) | Species | Drug product | Cmax | Tmax | AUC | Reference | |||
|---|---|---|---|---|---|---|---|---|---|
| Bim | BimA | Bim | BimA | Bim | BimA | ||||
| Plain drug solution | |||||||||
| Topical (once daily for 21 days) | Human (cataract surgery patients) | Lumigan® (0.03 %) | 2.83 ± 0.57 ng/mL | 12.84 ± 6.82 ng/ml | 1 hr | 2 hr | 6.82 ng.hr/mL (0–5 hr) | 30.51 ng.hr/mL (0–5 hr) | Faulkner R et al., 2010 |
| Topical (single dose) | Human (cataract surgery patients) | Lumigan® (0.03 %) | 2.74 ± 1.50 ng/mL | 2.78 ±1.37 ng/mL | l hr | 3 hr | NR | NR | Cantor et al. 2007 |
| Topical (once daily for 4 days) | New Zealand white rabbit | Lumigan® (0.01 %) | NR (BLQ by 1 hr) | 13.9 ± 1.8 ng/mL | NR | 1 hr | NR | 42.8±3.1 ng.hr/mL (0–8 hr) | Shen et al. 2017 |
| Topical (twice daily for 3 days + single dose on day 4) | New Zealand white rabbit | Lumigan® (0.01 %) | NR (BLQ by 1 hr) | 18.3 ± 2.7 ng/mL | NR | 1 hr | NR | 62.3±4.8 ng.hr/mL (0–8 hr) | Shen et al. 2017 |
| Topical (single dose) | Pigmented rabbit (HY79b) | Bimatoprost (0.03 %) | 12.11 ± 21.72 ng/mL | 29.58 ± 26.37 ng/mL | l hr | l hr | 12.31 ng.hr/mL (0.25–24 hr) | 98.79 ng.hr/mL (0.25–24 hr) | Shafiee et al. 2013 |
| Topical (single dose) | Pigmented rabbit (HY79b) | Bimatoprost (0.03%) formulated in DuraSite | 26.57 ± 19.16 ng/mL | 103.4 ± 42.36 ng/mL | 0.5 hr | 2 hr | 24.29 ng.hr/mL (0.25–24 hr) | 302.6 ng.hr/mL (0.25–24 hr) | Shafiee et al. 2013 |
| Topical (single dose) | Cynomolgus monkey | Bimatoprost (0.1 %) | 41.8 ng/g=mL | NR | 0.5 hr | NR | 110 ng.hr/g (0–24 hr) | NR | Woodward et al. 2003 |
| Topical (twice daily for 9.5 days) | Cynomolgus monkey | Bimatoprost (0.1 %) | 14.2 ng/g=mL | NR | 6 hr | NR | 102 ng.hr/g (0–24 hr) | NR | Woodward et al. 2003 |
| Topical (once daily for 7 days) | Beagle dog | Lumigan® (0.03 %) | 0.285 ± 0.166 ng/g | 3.29 ± 0.35 ng/g | l hr | 9 hr | 1.45 ± 0.41 ng.hr/mL (0–9 hr) | 18.6 ± 2.6 ng.hr/mL (0–9 hr) | Seal et al. 2019 |
| Sustained-release implant | |||||||||
| Intracameral (single dose) | Beagle dog | Bimatoprost sustained release implant (15 μg) | 22.9 ± 19.6 ng/g | 1.27 ± 0.30 ng/g | 27 day | 52 day | 727 ± 511 ng.day/mL (0–6 month) | 44.0 ± 6.6 ng.day/mL (0–6 month) | Seal et al. 2019 |
| Intracameral (single dose) | Beagle dog | Bimatoprost sustained release implant (8 μg) | 3.92 ng/mL* | 1.83 ng/mL* | 11 week* | 11 week* | 25.19 ng.day/mL (2–14 week)* | 11.28 ng.day/mL (2–14 week)* | Shen J et al. 2020 |
| Intracameral (single dose) | Beagle dog | Bimatoprost sustained release implant (15 μg) | 4.61 ng/mL* | 1.26 ng/mL* | 11 week* | 9 week* | 34.75 ng.day/mL (2–14 week)* | 9.70 ng.day/mL (2–14 week)* | Shen J et al. 2020 |
| Intracameral (single dose) | Beagle dog | Bimatoprost sustained release implant (30 μg) | 8.61 ng/mL* | 1.95 ng/mL* | 11 week* | 11 week* | 65.83 ng.day/mL (2–14 week)* | 15.51 ng.day/mL (2–14 week)* | Shen J et al. 2020 |
| Intracameral (single dose) | Beagle dog | Bimatoprost sustained release implant (60 μg) | 10.80 ng/mL* | 3.61 ng/mL* | 7 week* | 11 week* | 85.06 ng.day/mL (2–14 week)* | 29.35 ng.day/mL (2–14 week)* | Shen J et al. 2020 |
*
indicates that parameters are estimated/extracted.