Pharmacokinetic parameters of atovaquone following a loading intravenous bolus dose of 2.5 mg/kg followed by a continuous infusion of 0.1 (mg/kg)/hour in P-gp, Bcrp, Mrp2, Bsep knockout, and wild-type male Sprague-Dawley rats
Biliary excretion rate was calculated as an average from 4 to 30 hours in all rat groups. Liver Kp was calculated as a ratio of atovaquone liver to blood concentration at 30 h. Mean ± S.D., n = 4–6.
| Pharmacokinetic Parameters | Wild Type | P-gp Knockout | Bcrp Knockout | Mrp2 Knockout | Bsep Knockout |
|---|---|---|---|---|---|
| AUC(0–30) (μmol•h/ml) | 0.45 ± 0.05 | 0.44 ± 0.05 | 0.44 ± 0.01 | 0.34 ± 0.06 | 0.46 ± 0.06 |
| Bile recovery (nmol) | 235 ± 61 | 241 ± 33 | 194 ± 32 | 301 ± 108 | 340 ± 46 |
| S.S. biliary excretion rate (nmol/h) | 6.9 ± 1.2 | 7.0 ± 0.7 | 5.2 ± 0.9 | 9 ± 4 | 9.6 ± 1.7 |
| S.S. liver Conc. (µM) | 5.3 ± 0.7 | 5.4 ± 0.7 | 5.1 ± 0.8 | 4.3 ± 0.6 | 4.5 ± 0.7 |
| S.S. Liver Kp | 0.36 ± 0.05 | 0.38 ± 0.04 | 0.35 ± 0.06 | 0.40 ± 0.08 | 0.32 ± 0.02 |
| S.S. biliary clearance [(ml/min)/kg] | 0.029 ± 0.007 | 0.029 ± 0.005 | 0.024 ± 0.003 | 0.06 ± 0.02 | 0.04 ± 0.01 |
| S.S. canalicular clearance [(ml/min)/kg] | 0.07 ± 0.01 | 0.07 ± 0.02 | 0.06 ± 0.01 | 0.14 ± 0.03* | 0.12 ± 0.04 |
S.S., steady state. *P < 0.05.