Dose | Sex/N | Dose Day | Matrix | MET-1 U-102466 Conjugate | MET-2 U-102466 | MET-32-b U-96183 Conjugate | MET-42-c | MET-5 U-96183 | MET-6 | MET-7 | MET-8 | DLV |
---|---|---|---|---|---|---|---|---|---|---|---|---|
mg/kg/day | ||||||||||||
10 | M /3 | 1 | Bile | 6.3 ± 2.4 | 7.1 ± 1.3 | 9.1 ± 3.0 | 0.65 ± 0.60 | 4.5 ± 0.4 | 12.2 ± 1.0 | 5.1 ± 0.6 | 5.5 ± 1.8 | 0.44 ± 0.31 |
Urine | 0.04 ± 0.07 | 4.2 ± 0.5 | 0.42 ± 0.73 | 2.3 ± 1.9 | 12.0 ± 1.5 | ND2-d | 0.03 ± 0.05 | ND | ND | |||
Feces | 6.7 ± 3.3 | 0.91 ± 0.65 | ND | ND | ND | ND | 2.0 ± 0.7 | ND | ND | |||
Total | 13.0 ± 1.0 | 12.1 ± 0.2 | 9.6 ± 2.5 | 2.9 ± 2.0 | 16.5 ± 1.9 | 12.2 ± 1.0 | 7.1 ± 0.3 | 5.5 ± 1.8 | 0.44 ± 0.31 | |||
100 | M /3 | 1 | Bile | 2.8 ± 0.5 | 6.0 ± 1.6 | 3.4 ± 0.3 | 1.8 ± 0.3 | 3.2 ± 1.1 | 6.2 ± 0.5 | 2.9 ± 0.3 | 3.2 ± 1.1 | 0.48 ± 0.35 |
Urine | ND | 2.8 ± 0.5 | ND | 2.2 ± 0.6 | 8.4 ± 1.8 | ND | ND | ND | ND | |||
Feces | 12.0 ± 0.3 | 2.9 ± 0.1 | ND | ND | 1.8 ± 0.8 | ND | 12.6 ± 0.7 | ND | 1.3 ± 2.3 | |||
Total | 14.8 ± 0.5 | 11.7 ± 1.3 | 3.4 ± 0.3 | 3.9 ± 0.9 | 13.4 ± 0.7 | 6.2 ± 0.5 | 15.6 ± 0.8 | 3.2 ± 1.1 | 1.8 ± 2.6 | |||
20 | M /4 | 1 | Urine | 0.35 ± 0.12 | 1.7 ± 0.2 | ND | 0.31 ± 0.07 | 10.3 ± 0.8 | ND | 0.09 ± 0.06 | ND | ND |
F /4 | ND | 1.1 ± 0.4 | ND | 0.39 ± 0.05 | 11.5 ± 2.6 | 0.30 ± 0.38 | 0.20 ± 0.18 | ND | 0.11 ± 0.14 | |||
250 | M /4 | 1 | Urine | 0.02 ± 0.03 | 0.86 ± 0.07 | ND | 0.23 ± 0.06 | 6.2 ± 0.4 | 0.02 ± 0.03 | 0.22 ± 0.27 | ND | 0.47 ± 0.68 |
F /4 | ND | 0.48 ± 0.29 | ND | 0.23 ± 0.21 | 5.3 ± 2.7 | 0.03 ± 0.05 | 0.13 ± 0.05 | ND | 0.26 ± 0.11 | |||
20 | M /4 | 10 | Urine | 0.23 ± 0.14 | 1.7 ± 0.2 | ND | 0.37 ± 0.15 | 12.1 ± 1.8 | ND | 0.12 ± 0.09 | ND | 0.06 ± 0.07 |
F /4 | ND | 0.88 ± 0.18 | ND | 0.27 ± 0.15 | 8.4 ± 1.1 | 0.04 ± 0.03 | 0.03 ± 0.07 | ND | 0.12 ± 0.16 | |||
250 | M /4 | 10 | Urine | 0.03 ± 0.03 | 0.63 ± 0.06 | ND | 0.22 ± 0.08 | 4.7 ± 1.0 | 0.02 ± 0.02 | 0.06 ± 0.01 | ND | 0.19 ± 0.07 |
F /4 | ND | 0.55 ± 0.04 | ND | 0.27 ± 0.15 | 6.2 ± 2.1 | 0.01 ± 0.02 | 0.02 ± 0.04 | ND | 0.48 ± 0.23 |
↵2-a Mean ± SD in percentage of administered dose; values for feces were corrected for extraction recovery.
↵2-b MET-3 was tentatively characterized as a thermally labile conjugate of desalkyl delavirdine (U-96183).
↵2-c MET-4 represents a mixture of three metabolites: N-sulfamate desalkyl delavirdine (MET-4a), 6′-sulfate desalkyl delavirdine (MET-4b), and 4′-sulfate desalkyl delavirdine (MET-4d).
↵2-d ND, not detectable (peak area <50 dpm).