First-Pass CYP3A-Mediated Metabolism of Midazolam in the Gut Wall and Liver in Preterm Neonates

Brussee, Janneke M.Leiden Univ, LACDR, Div Syst Biomed & Pharmacol, Leiden, Netherlands (författare)

To predict first-pass and systemic cytochrome P450 (CYP) 3A-mediated metabolism of midazolam in preterm neonates, a physiological population pharmacokinetic model was developed describing intestinal and hepatic midazolam clearance in preterm infants. On the basis of midazolam and 1-OH-midazolam concentrations from 37 preterm neonates (gestational age 26-34 weeks) receiving midazolam orally and/or via a 30-minute intravenous infusion, intrinsic clearance in the gut wall and liver were found to be very low, with lower values in the gut wall (0.0196 and 6.7 L/h, respectively). This results in a highly variable and high total oral bioavailability of 92.1% (range, 67-95%) in preterm neonates, whereas this is around 30% in adults. This approach in which intestinal and hepatic clearance were separately estimated shows that the high bioavailability in preterm neonates is explained by, likely age-related, low CYP3A activity in the liver and even lower CYP3A activity in the gut wall.

Yu, HuixinLeiden Univ, LACDR, Div Syst Biomed & Pharmacol, Leiden, Netherlands (författare)
Krekels, Elke H. J.Leiden Univ, LACDR, Div Syst Biomed & Pharmacol, Leiden, Netherlands (författare)
de Roos, BerendLeiden Univ, LACDR, Div Syst Biomed & Pharmacol, Leiden, Netherlands (författare)
Brill, Margreke JEUppsala universitet,Institutionen för farmaceutisk biovetenskap(Swepub:uu)marbr178 (författare)
van den Anker, Johannes N.Univ Basel, Childrens Hosp, Div Paediat Pharmacol & Pharmacometr, Basel, Switzerland;Sophia Childrens Univ Hosp, Erasmus MC, Intens Care & Dept Pediat Surg, Rotterdam, Netherlands;Childrens Natl Hlth Syst, Div Clin Pharmacol, Washington, DC USA (författare)
Rostami-Hodjegan, AminSimcyp Ltd, Sheffield, S Yorkshire, England;Univ Manchester, Ctr Appl Pharmacokinet Res, Manchester, Lancs, England (författare)
de Wildt, Saskia N.Radboud Univ Nijmegen, Dept Pharmacol & Toxicol, Med Ctr, Nijmegen, Netherlands;Sophia Childrens Univ Hosp, Erasmus MC, Intens Care & Dept Pediat Surg, Rotterdam, Netherlands (författare)
Knibbe, Catherijne A. J.Leiden Univ, LACDR, Div Syst Biomed & Pharmacol, Leiden, Netherlands;St Antonius Hosp, Dept Clin Pharm, Nieuwegein, Netherlands (författare)
Leiden Univ, LACDR, Div Syst Biomed & Pharmacol, Leiden, NetherlandsInstitutionen för farmaceutisk biovetenskap (creator_code:org_t)

Av författaren/redakt...: Brussee, Janneke ...; Yu, Huixin; Krekels, Elke H. ...; de Roos, Berend; Brill, Margreke ...; van den Anker, J ...; visa fler...; Rostami-Hodjegan ...; de Wildt, Saskia ...; Knibbe, Catherij ...; visa färre...

Om ämnet

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinska och f ...; och Farmaceutiska ve ...

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.