Table 3. Pharmacokinetic parameters of olaparib alone (day 1), olaparib in the presence of PLD (day 2), and PLD 1-h infusion by olaparib administration schedule (mean±s.d.).
| |
|
Pharmacokinetic parameters of olaparib |
|
|---|---|---|---|
| Olaparib (mg bid) | n | AUC0–10 h (μg × h ml−1) | Cmax (μg ml−1) |
|
50 | |||
| Day 1 alone | 3 | 8.7±5.8 | 1.8±1.1 |
| Day 2+PLD |
|
— |
1.4±0.7 |
|
100 | |||
| Day 1 alone | 3 | 6.8±2.7 | 1.7±0.8 |
| Day 2+PLD |
|
9.4±3.0 |
2.2±1.0 |
|
200 | |||
| Day 1 alone | 2 | 29.5 (12.2, 46.9) | 5.6 (3.3, 7.9) |
| Day 2+PLD |
3 |
46.2±52.0 |
5.2±2.8 |
|
400 | |||
| Day 1 alone | 11 | 25.9±9.0 | 5.1±1.7 |
| Day 2+PLD | 35.2±17.1a | 6.6±2.0a | |
| |
|
Pharmacokinetic parameters of PLD |
|||||
|---|---|---|---|---|---|---|---|
| Olaparib (mg bid) | n | AUC0–24 h(μM × h) | AUC0-inf(μM × h) | Cmax(μM) | T½(h) | CLTB(l) | Vss(l) |
|
50 | |||||||
| Q7 |
3 |
732±42 |
4359±998 |
36.3±0.8 |
77±7 |
17±4 |
1.5±0.1 |
|
100 | |||||||
| Q7 | 3 | 623 (574–672) | 4885 (4232–5537) | 38.9±16.4 | 83±24 | 15±3 | 1.6±0.6 |
| Q28 |
3 |
566±50 |
4129 |
30.0±0.5 |
82±13 |
22±5 |
2.0±0.02 |
|
200 | |||||||
| Q7 | 2 | 624 (609–639) | 3846 (3823–3868) | 33.9 (34.2–33.6) | 67 (69–65) | 18 (18–18) | 1.6 (1.7–1.5) |
| Q28 |
3 |
658±46 |
3968±44 |
36.2±3.1 |
74±10 |
17±1 |
1.5±0.3 |
|
400 | |||||||
| Q7 | 11 | 562±108 | 3319±707b | 30.6±4.3 | 72±12 | 23±6c | 2.0±0.3 |
| Q28 | 12 | 609±104 | 4209±928b | 33.5±5.2 | 77±13 | 18±4c | 1.7±0.4 |
Abbreviations: AUC=area under the plasma concentration–time curve; Cmax=maximum concentration; CLTB=total body clearance; PLD=pegylated liposomal doxorubicin; Q7=7-day dosing of olaparib; Q28=28-day dosing of olaparib; T½,=half-life; Vss=distribution volume at steady state.
a
P<0.01 by Student's t-test for paired data.
b
P=0.0276.
c
P=0.0233 by Student's t-test for unpaired data.