BACKGROUND: Drug disposition is altered by pregnancy and the peripartum period but data on intravenous ketorolac pharmacokinetics following caesarean delivery have not been previously reported. METHODS: At the end of caesarean delivery, women received an intravenous bolus of ketorolac tromethamine 30 mg (immediate postpartum, Group IP). Plasma samples were collected at 1, 2, 4, 6 and 8h. A similar pharmacokinetic study was repeated in a subgroup of these women 4-5 months after delivery (late postpartum, Group LP) and in a group of unrelated, healthy non-pregnant female volunteers (controls, Group C). A non-compartmental linear disposition model was applied to analyse individual ketorolac time-concentration profiles. Results at delivery were compared with controls using unpaired or paired statistics as appropriate. Covariates of pharmacokinetic estimates at delivery were examined. RESULTS: Thirty-nine women were studied at caesarean delivery, of whom eight were re-evaluated 4-5 months later. In addition, eight volunteers were studied. Clearance in Group IP was higher compared to Groups LP and C (2.11 vs. 1.43 and 1.07 L/h·m(2) respectively, P<0.05). Volume of distribution was also increased in Group IP compared to Groups LP and C (0.24 vs. 0.16 and 0.17 L/kg respectively, P<0.05). No significant covariates of pharmacokinetic estimates, including gestational age, preterm vs. term, twin vs. singleton and maternal co-morbidity, were seen in Group IP. CONCLUSIONS: Ketorolac clearance and distribution volume are significantly increased following caesarean delivery. These data provide pharmacokinetic estimates on which to base studies on post caesarean analgesia.
BACKGROUND: Drug disposition is altered by pregnancy and the peripartum period but data on intravenous ketorolac pharmacokinetics following caesarean delivery have not been previously reported. METHODS: At the end of caesarean delivery, women received an intravenous bolus of ketorolac tromethamine 30 mg (immediate postpartum, Group IP). Plasma samples were collected at 1, 2, 4, 6 and 8h. A similar pharmacokinetic study was repeated in a subgroup of these women 4-5 months after delivery (late postpartum, Group LP) and in a group of unrelated, healthy non-pregnant female volunteers (controls, Group C). A non-compartmental linear disposition model was applied to analyse individual ketorolac time-concentration profiles. Results at delivery were compared with controls using unpaired or paired statistics as appropriate. Covariates of pharmacokinetic estimates at delivery were examined. RESULTS: Thirty-nine women were studied at caesarean delivery, of whom eight were re-evaluated 4-5 months later. In addition, eight volunteers were studied. Clearance in Group IP was higher compared to Groups LP and C (2.11 vs. 1.43 and 1.07 L/h·m(2) respectively, P<0.05). Volume of distribution was also increased in Group IP compared to Groups LP and C (0.24 vs. 0.16 and 0.17 L/kg respectively, P<0.05). No significant covariates of pharmacokinetic estimates, including gestational age, preterm vs. term, twin vs. singleton and maternal co-morbidity, were seen in Group IP. CONCLUSIONS:Ketorolac clearance and distribution volume are significantly increased following caesarean delivery. These data provide pharmacokinetic estimates on which to base studies on post caesarean analgesia.
Authors: Pyry A Välitalo; Heidi Kemppainen; Aida Kulo; Anne Smits; Kristel van Calsteren; Klaus T Olkkola; Jan de Hoon; Catherijne A J Knibbe; Karel Allegaert Journal: Br J Clin Pharmacol Date: 2017-05-14 Impact factor: 4.335
Authors: Aida Kulo; Sarah Hendrickx; Jan de Hoon; Nedzad Mulabegovic; Kristel van Calsteren; Rene Verbesselt; Karel Allegaert Journal: Eur J Drug Metab Pharmacokinet Date: 2012-11-21 Impact factor: 2.441
Authors: Aida Kulo; Anne Smits; Sanita Maleškić; Marc Van de Velde; Kristel Van Calsteren; Jan De Hoon; Rene Verbesselt; Jan Deprest; Karel Allegaert Journal: Bosn J Basic Med Sci Date: 2017-02-21 Impact factor: 3.363