Table 3.
Drug concentrations in vaginal tissues, vaginal fluids, and rectal fluids from N = 6 female pigtailed macaques treated vaginally with 0.5 or 1.5 ml IQB4012 gel containing 1% wt/wt each of IQP-0528 and TFV
| IQP-0528 median drug concentration (min—max) | |||||||
|---|---|---|---|---|---|---|---|
| Vaginal tissues (ng/g) | Vaginal fluids (ng/ml) | Rectal fluids (ng/ml) | |||||
| Proximalb | Medial | Distal | Proximal | Distal | - | ||
| 0.5 ml Gel | 2 h | N/A | N/A | N/A | 6,758,116 (2474–46,372,550) | 2,319,091 (BLLOQ-17,500,000) | 20 (BLLOQ-1583) |
| 4 h | 128,443 (323–2,344,444) | 290,086 (887–1,503,333) | 95,000 (BLLOQ-1,839,7441 | 6,014,248 (1946–43,815,790) | 2,038,462 (BLLOQ-17,891,890) | 77 (BLLOQ-37,600) | |
| 24 h | 43,878 (1622–962,500) | 22,527 (714–458,763) | 20,915 (545–224,753) | 257,071 (BLLOQ-5,200,000) | 328,205 (BLLOQ-11,034,8801 | 199 (BLLOQ-6288) | |
| Ratio (measured/EC50a) | N/A | N/A | N/A | 2 h-6,758,116 | 2 h-2,319,091 | 2 h-20 | |
| 4 h-6,014,248 | 4 h-2,038,462 | 4 h-77 | |||||
| 24 h-257,071 | 24 h-328,205 | 24 h-199 | |||||
| 1.5 ml Gel | 2 h | N/A | N/A | N/A | 5,654,526 (4714–57,865,860) | 6,022,388 (BLLOQ-83,227,270) | 1004 (BLLOQ-56,000) |
| 4 h | 611,547 (449–4,760,736) | 739,886 (278–6,377,273) | 213,000 (BLLOQ-6,404,545) | 4,925,373 (BLLOQ-60,750,000) | 4,636,643 (BLLOQ-173,000,000) | 411 (BLLOQ-120,000) | |
| 24 h | 23,873 (1489–1,054,000) | 46,315 (1087–2,031,746) | 24,167 (BLLOQ-517,742) | 475,000 (BLLOQ-159,000,000) | 375,385 (BLLOQ-32,714,2901 | 1258 (BLLOQ-26,475) | |
| Ratio (measured/EC50) | N/A | N/A | N/A | 2 h-5,654,526 | 2 h-6,022,388 | 2 h-1004 | |
| 4 h-4,925,373 | 4 h-4,636,643 | 4 h-411 | |||||
| 24 h-475,000 | 24 h-375,385 | 24 h-1258 | |||||
| TFV median drug concentration (min—maxi | |||||||
| Vaginal tissues (ng/g) | Vaginal fluids (ng/ml) | Rectal fluids (ng/ml) | |||||
| Proximal | Medial | Distal | Proximal | Distal | - | ||
| 0.5 ml Gel | 2 h | N/A | N/A | N/A | 158,146 (BLLOQ2-3,025,157) | 232,128 (BLLOQ-3,968,750) | 80 (BLLOQ-104) |
| 4 h | 4486 (484–60,000) | 8857 (714–130,909) | 13,367 (BLLOQ-72,051) | 124,304 (BLLOQ-12,113,400) | 132,458 (BLLOQ-1,971,250) | 69 (BLLOQ-176) | |
| 24 h | 16,932 (270–61,786) | 3553 (BLLOQ-30,000) | 5906 (BLLOQ-37,030) | 48,942 (BLLOQ-9,600,000) | 18,709 (BLLOQ-267,794) | 53 (BLLOQ-139) | |
| Ratio (measured/EC50) | N/A | N/A | N/A | 2 h-230 | 2 h-1009 | 2 h-0.12 | |
| 4 h-180 | 4 h-192 | 4 h-0 | |||||
| 24 h-71 | 24 h-27 | 24 h-0.08 | |||||
| 1.5 ml Gel | 2 h | N/A | N/A | N/A | 30,394 (BLLOQ-1,162,921) | 37,183 (BLLOQ-1,776,786) | 138 (BLLOQ-726) |
| 4 h | 35,081 (225–1,613,636) | 10,181 (417–835,784) | 19,250 (BLLOQ-1,200,000) | 54,269 (BLLOQ-2,645,455) | 152,548 (BLLOQ-6,993,750) | 156 (BLLOQ-624) | |
| 24 h | 2390 (BLLOQ202.466) | 12,200 (BLLOQ-546,825) | 5377 (BLLOQ-23,226) | 17,976 (BLLOQ-2,883,333) | 56,977 (BLLOQ-830,952) | 127 (BLLOQ-791) | |
| Ratio (measured/EC50) | N/A | N/A | N/A | 2 h-44.1 | 2 h-54 | 2 h-0.20 | |
| 4 h-78.8 | 4 h-221 | 4 h-0.23 | |||||
| 24 h-26.1 | 24 h-82.7 | 24 h-0.18 | |||||
N/A not applicable, BLLOQ below lower limit of quantitation
a
EC50 values of 1.0 ng/ml for IQP-0528 and 689 ng/ml for TFV were used to calculate measured drug/EC50 ratios
b
P,M, and D refer to location of sample collection in relation to cervix. P proximal, M medial, D distal