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First-Pass CYP3A-Me...
First-Pass CYP3A-Mediated Metabolism of Midazolam in the Gut Wall and Liver in Preterm Neonates
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- Brussee, Janneke M. (författare)
- Leiden Univ, LACDR, Div Syst Biomed & Pharmacol, Leiden, Netherlands
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- Yu, Huixin (författare)
- Leiden Univ, LACDR, Div Syst Biomed & Pharmacol, Leiden, Netherlands
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- Krekels, Elke H. J. (författare)
- Leiden Univ, LACDR, Div Syst Biomed & Pharmacol, Leiden, Netherlands
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- de Roos, Berend (författare)
- Leiden Univ, LACDR, Div Syst Biomed & Pharmacol, Leiden, Netherlands
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- Brill, Margreke JE (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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- van den Anker, Johannes N. (författare)
- 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
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- Rostami-Hodjegan, Amin (författare)
- Simcyp Ltd, Sheffield, S Yorkshire, England;Univ Manchester, Ctr Appl Pharmacokinet Res, Manchester, Lancs, England
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- de Wildt, Saskia N. (författare)
- Radboud Univ Nijmegen, Dept Pharmacol & Toxicol, Med Ctr, Nijmegen, Netherlands;Sophia Childrens Univ Hosp, Erasmus MC, Intens Care & Dept Pediat Surg, Rotterdam, Netherlands
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- Knibbe, Catherijne A. J. (författare)
- Leiden Univ, LACDR, Div Syst Biomed & Pharmacol, Leiden, Netherlands;St Antonius Hosp, Dept Clin Pharm, Nieuwegein, Netherlands
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(creator_code:org_t)
- 2018-05-10
- 2018
- Engelska.
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Ingår i: CPT. - : WILEY. - 2163-8306. ; 7:6, s. 374-383
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://ascpt.online...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
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- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
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