Table 4.
Desirability of antibiotic‒XueBiJing compound pairs.
| Antibiotic‒XueBiJing pair | Interacting protein | Inhibition DDI index | Potential outcome | Remark |
|---|---|---|---|---|
| Cefoperazone (A8)‒senkyunolide I (X5) | UGT2B15 | 0.12 | Decreased glucuronidation of and increased systemic exposure to X5. For X5, its unbound Cmax 0.2 μmol/L (Table 1) is less than its effective concentration 10 μmol/L (Supporting Information Table S2), so inhibition of UGT2B15 by these antibiotics at the clinically relevant doses would lead to the desirable concentration. | Probably desirable due to the low baseline level of systemic exposure to X5. |
| Penicillin G (A15)‒senkyunolide I (X5) | 0.43–0.74 | |||
| Piperacillin (A13)‒senkyunolide I (X5) | 0.56 | |||
| Voriconazole (A45)‒senkyunolide I (X5) | 0.75 | |||
| Cefoxitin (A20)‒senkyunolide I (X5) | 1.28 | |||
| Oxacillin (A17)‒protocatechuic aldehyde | ALDH | 0.11 | Decreased systemic exposure to the metabolite X11 and increased methylated protocatechuic aldehyde. For X11, its unbound Cmax 0.03 μmol/L (Table 1) is low as compared with its effective concentrations 1–130 μmol/L (Supporting Information Table S2); inhibition of ALDH by these antibiotics at the clinically relevant doses would further decrease its concentration. | Undesirable but probably of limited therapeutic relevance due to the low baseline level of systemic exposure to X11. |
| Ampicillin (A16)‒protocatechuic aldehyde | 0.17 | |||
| Ceftazidime (A7)‒protocatechuic aldehyde | 0.19 | |||
| Flucloxacillin (A19)‒protocatechuic aldehyde | 0.62 | |||
| Meropenem (A2)‒protocatechuic aldehyde | 0.78 | |||
| Penicillin G (A15)‒protocatechuic aldehyde | 1.24–2.14 | |||
| Imipenem (A1)‒protocatechuic aldehyde | 2.14 | |||
| Flucloxacillin (A19)‒tanshinol (X8) | OAT1 | 0.16 | Decreased renal excretion of and increased systemic exposure to X8. For X8, its unbound Cmax 0.1 μmol/L (Table 1) is less than its effective concentrations 1–25 μmol/L (Supporting Information Table S2), so inhibition of OAT1/2 by these antibiotics at the clinically relevant doses would lead to the desirable concentrations. | Probably desirable due to the low baseline level of systemic exposure to X8. |
| Voriconazole (A45)‒tanshinol (X8) | 0.22 | |||
| Ticarcillin (A14)‒tanshinol (X8) | 0.26 | |||
| Cefamandole (A11)‒tanshinol (X8) | 0.33 | |||
| Penicillin G (A15)‒tanshinol (X8) | 0.38–0.66 | |||
| Cefoperazone (A8)‒tanshinol (X8) | 0.95–2.44 | |||
| Carbenicillin (A18)‒tanshinol (X8) | 1.31 | |||
| Levofloxacin (A31)‒tanshinol (X8) | OAT2 | 0.36 | ||
| Oxacillin (A17)‒tanshinol (X8) | OAT1/2 | 0.52/0.11 | ||
| Piperacillin (A13)‒tanshinol (X8) | 0.75/0.37 | |||
| Ciprofloxacin (A32)‒tanshinol (X8) | 1.96/0.55 | |||
| Trimethoprim (A37)‒salvianolic acid B (X10) | OATP1B3 | 0.12 | Decreased hepatobiliary excretion of and increased systemic exposure to X10. For X10, its unbound Cmax 0.003 μmol/L (Table 1) is less than its effective concentrations 0.1–1.4 μmol/L (Supporting Information Table S2), so inhibition of OATP1B3 by these antibiotics at the clinically relevant doses would lead to the desirable concentrations. | Probably desirable due to the low baseline level of systemic exposure to X10. |
| Amphotericin B (A42)‒salvianolic acid B (X10) | 0.22 | |||
| Moxifloxacin (A33)‒salvianolic acid B (X10) | 0.29–0.41 | |||
| Clindamycin (A35)‒salvianolic acid B (X10) | 0.30 | |||
| Caspofungin (A41)‒salvianolic acid B (X10) | 0.35 | |||
| Erythromycin (A34)‒salvianolic acid B (X10) | 0.35–1.04 | |||
| Teicoplanin (A26)‒salvianolic acid B (X10) | 0.60 | |||
| Ceftriaxone (A6)‒salvianolic acid B (X10) | 0.68 | |||
| Ciprofloxacin (A32)‒salvianolic acid B (X10) | 0.69 | |||
| Flucloxacillin (A19)‒salvianolic acid B (X10) | 1.07 | |||
| Cefamandole (A11)‒salvianolic acid B (X10) | 1.70 | |||
| Cefoperazone (A8)‒salvianolic acid B (X10) | 1.72–4.43 | |||
| Cefotaxime (A9)‒salvianolic acid B (X10) | 1.81–2.14 | |||
| Voriconazole (A45)‒salvianolic acid B (X10) | 2.16 | |||
| Rifamcin (A39)‒salvianolic acid B (X10) | 2.63 | |||
| Cefoxitin (A20)‒salvianolic acid B (X10) | 2.81 | |||
| Oxacillin (A17)‒salvianolic acid B (X10) | 4.64 | |||
| Penicillin G (A15)‒salvianolic acid B (X10) | 6.8–11.8 | |||
| Ampicillin (A16)‒salvianolic acid B (X10) | 8.55 |