PP-21 Enantiomer-specific ketorolac pharmacokinetics in young women, including pregnancy and postpartum

Abstract

Background Ketorolac, a potent non-steroidal anti-in-flammatory drug, is a chiral substance. Racemic ketorolac clearance is significantly higher at delivery, but S-ketorolac disposition determines the analgesic effects. We aimed to document the impact of pregnancy and postpartum on enantiomer-specific (S and R) ketorolac pharmacokinetics (PK) in young women. Methods Observations shortly following caesarean de-livery (n=39) were pooled with data in subgroup of these women (n=8/39) four months afterwards (‘postpartum’) and with 8 healthy female volunteers, resulting in 47 un-paired and 8 paired PK estimates. All women received single intravenous bolus of ketorolac tromethamine (30 mg). Five (at 1, 2, 4, 6, 8 hour) plasma samples were collected and plasma concentrations were determined using HPLC method. Enantiomer-specific PKs were calculated using PKSolver. Results Unpaired analysis documented that median distribution volume at steady state (Vss) for S-and R-ke-torolac was significantly higher in women following cae-sarean delivery (n=31) compared to postpartum (n=8) (S-ketorolac: 12.79 vs. 7.84 L, p=0.011; R-ketorolac: 8.96 vs. 5.86 L, p=0.001) or to healthy female volunteers (n=8). (S-ketorolac: 12.79 vs. 9.14 L, p=0.002; R-ketorolac: 8.96 vs. 5.51 L, p Conclusion Pregnancy affects S-, R-and S/R-ketorolac disposition. This is of clinical relevance since S-ketorolac (analgesia) CL is even more increased compared to R-ke-torolac CL and S/R-ketorolac CL ratio is higher following delivery compared to postpartum or to healthy female volunteers. For definitive physiological state-specific dos-ing recommendations in women, we encourage future repeated dosing pharmacokinetic studies in this specific population.