Developmental changes in the extent of drug binding to rat plasma proteins

Qiu, Fiona; Dzięgielewska, Katarzyna M.; Huang, Yifan; Habgood, Mark D.; Fitzpatrick, Georgia; Saunders, Norman

doi:10.1038/s41598-023-28434-1

Cited by 7 publications

(13 citation statements)

References 72 publications

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“…In a more limited study of 17 drugs all were found to have free fractions between <1-9%, but rat plasma showed much higher free fractions for the same drugs of up to 70% (Colclough et al 2023). Qiu et al (2023) reported a free fraction of 65-85% for several drugs in adult rats. However, for highly lipid soluble drugs such as ivacaftor the free fraction is much smaller (<1%, Qiu et al 2023).…”

Section: Plasma Protein Binding Of Cannabidiolmentioning

confidence: 90%

“…In vitro: This method has been described before (Qiu et al 2023). Briefly, control, untreated timemated pregnant females at E19, E19 fetuses, P4 pups, P12 pups and non-pregnant adult females were deeply anaesthetised via i.p.…”

Section: Plasma Protein Binding Of Cannabidiolmentioning

confidence: 99%

“…Qiu et al (2023) reported a free fraction of 65-85% for several drugs in adult rats. However, for highly lipid soluble drugs such as ivacaftor the free fraction is much smaller (<1%, Qiu et al 2023). In the present study the free cannabidiol fraction was estimated to be around 15% (Table 9).…”

Section: Plasma Protein Binding Of Cannabidiolmentioning

confidence: 99%

“…As an indicator of placental transfer following maternal administration, we have compared levels of cannabidiol in the maternal and fetal circulations. Because binding of drugs by plasma proteins is thought to be an important determinant of their tissue distribution, including the brain (Qiu et al 2023) we have also determined cannabidiol plasma protein bound and unbound fractions at different ages and established that although albumin is the main protein binding the drug, this is most likely due to its relative abundance rather than greater affinity. As the main mechanism of action of cannabidiol is via interaction with the endocannabidiol system, as well as binding to specific central and peripheral receptors (Peng et al 2022), we have mined available rat RNA seq datasets of fetal, postnatal and adult brain and choroid plexus as well as E19 placenta (Koehn et al 2020) to determine developmental changes in the expression of 13 main cannabidiol receptors.…”

Section: Introductionmentioning

confidence: 99%

“…Binding of cannabidiol to rat plasma protein at different ages.Binding was estimated by an in vitro ultrafiltration method as described previously(Qiu et al 2023). …”

mentioning

confidence: 99%

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Entry of cannabidiol into the fetal, postnatal and adult rat brain.

et al. 2023

Preprint

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Cannabidiol is a major component of cannabis but without known psychoactive properties. A wide range of properties have been attributed to it, such as anti-inflammatory, analgesic, anti-cancer, anti-seizure and anxiolytic. However, being a fairly new compound in its purified form, little is known about cannabidiol brain entry, especially during development. Sprague Dawley rats at four developmental ages: embryonic day E19, postnatal day P4 and P12 and non-pregnant adult females were administered intraperitoneal cannabidiol at 10 mg/kg with [3H] labelled cannabidiol. To investigate the extent of placental transfer the drug was injected intravenously into E19 pregnant dams. Levels of [3H]-cannabidiol in blood plasma, cerebrospinal fluid and brain were estimated by liquid scintillation counting. Plasma protein binding of cannabidiol was identified by polyacrylamide gel electrophoresis and its bound and unbound fractions measured by ultrafiltration. Using available RNA-sequencing datasets of E19 rat brain, choroid plexus and placenta, as well as P5 and adult brain and choroid plexus, expression of 13 main cannabidiol receptors was analysed. Results showed that cannabidiol rapidly entered both the developing and adult brains. Entry into CSF was more limited. Its transfer across the placenta was substantially restricted as only about 50% of maternal blood plasma cannabidiol concentration was detected in fetal plasma. Albumin was the main, but not exclusive, cannabidiol binding protein at all ages. Several transcripts for cannabidiol receptors were expressed in age- and tissue-specific manner indicating that cannabidiol may have different functional effects in the fetal compared to adult brain.

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Section: Plasma Protein Binding Of Cannabidiolmentioning

confidence: 90%

Section: Plasma Protein Binding Of Cannabidiolmentioning

confidence: 99%

Section: Plasma Protein Binding Of Cannabidiolmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Binding of cannabidiol to rat plasma protein at different ages.Binding was estimated by an in vitro ultrafiltration method as described previously(Qiu et al 2023). …”

mentioning

confidence: 99%

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Entry of cannabidiol into the fetal, postnatal and adult rat brain.

et al. 2023

Preprint

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Entry of cannabidiol into the fetal, postnatal and adult rat brain

Fitzpatrick,

Huang,

Qiu

et al. 2024

Cell Tissue Res

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Cannabidiol is a major component of cannabis but without known psychoactive properties. A wide range of properties have been attributed to it, such as anti-inflammatory, analgesic, anti-cancer, anti-seizure and anxiolytic. However, being a fairly new compound in its purified form, little is known about cannabidiol brain entry, especially during development. Sprague Dawley rats at four developmental ages: embryonic day E19, postnatal day P4 and P12 and non-pregnant adult females were administered intraperitoneal cannabidiol at 10 mg/kg with [3H] labelled cannabidiol. To investigate the extent of placental transfer, the drug was injected intravenously into E19 pregnant dams. Levels of [3H]-cannabidiol in blood plasma, cerebrospinal fluid and brain were estimated by liquid scintillation counting. Plasma protein binding of cannabidiol was identified by polyacrylamide gel electrophoresis and its bound and unbound fractions measured by ultrafiltration. Using available RNA-sequencing datasets of E19 rat brain, choroid plexus and placenta, as well as P5 and adult brain and choroid plexus, expression of 13 main cannabidiol receptors was analysed. Results showed that cannabidiol rapidly entered both the developing and adult brains. Entry into CSF was more limited. Its transfer across the placenta was substantially restricted as only about 50% of maternal blood plasma cannabidiol concentration was detected in fetal plasma. Albumin was the main, but not exclusive, cannabidiol binding protein at all ages. Several transcripts for cannabidiol receptors were expressed in age- and tissue-specific manner indicating that cannabidiol may have different functional effects in the fetal compared to adult brain.

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