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Population pharmacokinetics and pharmacodynamics of Tranexamic acid in women undergoing caesarean delivery.
Li, Shuhui; Ahmadzia, Homa K; Guo, Dong; Dahmane, Elyes; Miszta, Adam; Luban, Naomi L C; Berger, Jeffrey S; James, Andra H; Wolberg, Alisa S; van den Anker, John N; Gobburu, Jogarao V S.
Afiliação
  • Li S; Center for Translational Medicine, School of Pharmacy, University of Maryland, Baltimore, M.D., USA.
  • Ahmadzia HK; Division of Maternal-Fetal Medicine, Department of Obstetrics & Gynecology, The George Washington University School of Medicine and Health Sciences, Washington, D.C., USA.
  • Guo D; School of Pharmacy, University of Maryland, Baltimore, M.D., USA.
  • Dahmane E; Center for Translational Medicine, School of Pharmacy, University of Maryland, Baltimore, M.D., USA.
  • Miszta A; Department of Pathology and Laboratory Medicine and UNC Blood Research Center, University of North Carolina, Chapel Hill, N.C., USA.
  • Luban NLC; Synapse Research Institute, Maastricht, the Netherlands.
  • Berger JS; Division of Hematology, Children's National Hospital, Washington, D.C., USA.
  • James AH; Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
  • Wolberg AS; Department of Anesthesiology and Critical Care Medicine, The George Washington University School of Medicine and Health Sciences, Washington, D.C., USA.
  • van den Anker JN; Division of Maternal-Fetal Medicine, Department of Obstetrics & Gynecology, Duke University, Durham, N.C., USA.
  • Gobburu JVS; Department of Pathology and Laboratory Medicine and UNC Blood Research Center, University of North Carolina, Chapel Hill, N.C., USA.
Br J Clin Pharmacol ; 87(9): 3531-3541, 2021 09.
Article em En | MEDLINE | ID: mdl-33576009
AIMS: The population pharmacokinetics (PK) and pharmacodynamics (PD) of tranexamic acid (TXA) have not been studied to prevent postpartum haemorrhage (PPH) in pregnant women. It is unclear which TXA dose assures sufficient PPH prevention. This study investigated population PK/PD of TXA in pregnant women who underwent caesarean delivery to determine the optimal prophylactic doses of TXA for future studies. METHODS: We analysed concentration (PK) and maximum lysis (PD) data from 30 pregnant women scheduled for caesarean delivery who received 5, 10 or 15 mg/kg of TXA intravenously using population approach. RESULTS: TXA PK was best described by a two-compartment model with first-order elimination and the following parameters: clearance (between-subject variability) of 9.4 L/h (27.7%), central volume of 10.1 L (47.4%), intercompartmental clearance of 22.4 L/h (66.7%), peripheral volume of 14.0 L (13.1%) and additive error of 1.4 mg/L. The relationship between TXA concentration and maximum lysis was characterized by a sigmoid Emax model with baseline lysis of 97%, maximum inhibition of 89%, IC50 of 6.0 mg/L (65.3%), hill factor of 8.5 (86.3%) and additive error of 7.3%. Simulations demonstrated that 500 and 650 mg of TXA maintained therapeutic targets for 30 minutes and 1 hour, respectively, in 90% of patients. CONCLUSION: This is the first population PK and PD study of TXA in pregnant women undergoing caesarean delivery. Our analysis suggests that a 650 mg dose provides adequate PPH prophylaxis up to 1 hour, which is less than the currently used 1000 mg of TXA in pregnant women.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ácido Tranexâmico / Hemorragia Pós-Parto / Antifibrinolíticos Tipo de estudo: Prognostic_studies Limite: Female / Humans / Pregnancy Idioma: En Revista: Br J Clin Pharmacol Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ácido Tranexâmico / Hemorragia Pós-Parto / Antifibrinolíticos Tipo de estudo: Prognostic_studies Limite: Female / Humans / Pregnancy Idioma: En Revista: Br J Clin Pharmacol Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos