Pharmacokinetics of tacrolimus, cyclosporin and azathioprine during pregnancy in kidney and liver transplant recipients.

Pharmacokinetics of tacrolimus, cyclosporin and azathioprine during pregnancy in kidney and liver transplant recipients. - Tacrolimus during pregnancy.

Status

Recruiting

Phases

Unknown

Study type

Observational

Source

NL-OMON

Registry ID

NL-OMON51032

Enrollment

Registered

2020-12-17

Start date

2021-08-23

Completion date

Unknown

Last updated

2025-09-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

kidney transplantation and liver transplantation

Interventions

There is no intervention.

Eligibility

Age

18 Years to 64 Years

Inclusion criteria

Inclusion criteria: -Kidney or liver transplantation in medical history -Tacrolimus OR ciclosporin AND/OR azathioprine based immunosuppressive regimen -Written informed consent Based on previous experiences with population pharmacokinetic model building,  the amount of 24 patients is sufficient to describe the pharmacokinetics during  pregnancy (for each medication type). Taking into consideration the already included participants before  the amendment, the drop outs and participants who are included during the  pregnancy, we estimate that around 90 patients will participate in the study.

Exclusion criteria

Exclusion criteria: • Age

Design outcomes

Primary

Measure	Time frame
The correlation between the plasma tacrolimus/ciclosporin concentration and whole blood concentration during pregnancy in kidney and liver transplant recipients.	—

Secondary

Measure	Time frame
Secondary study parameters focus on the change of the fraction of tacrolimus/ciclosporin in plasma relative to whole blood before, during and after pregnancy. - Relating the free tacrolimus/ciclosporin and whole blood levels to kidney function. - Assessing whether there is a difference in the pharmacokinetics and pharmacodynamics of kidney transplant compared to liver transplant recipients. - To describe the pharmacokinetics of tacrolimus before, during and after pregnancy in kidney and liver transplant recipients in a population pharmacokinetic model using data from the concentration of whole blood tacrolimus, plasma tacrolimus, AUCs, the tacrolimus concentration within CD3+ T lymphocytes, genotyping of CYP3A, ABCB1 and POR, and body composition; - To perform simulations with the population pharmacokinetic model in order to predict which dosages of the drugs are needed to obtain the target trough concentration, for future pregnant patients after kidney of liver transplantation before, during and after pregnancy; - To define the correlation between whole-blood tacrolimus/ciclosporine concentrations and intracellular tacrolimus/ciclosporine concentrations and plasma tacrolimus/ciclosporin concentrations (prior to conception and during gestation); - To determine drug concentrations in umbilical cord blood and analyze the tacrolimus placenta transfer ratio; - To determine the effect of maternal CYP3A4 and CYP3A5 genotype and foetal CYP3A7 genotype on drug concentrations;-To determine the effect of maternal TPMT and NUDT15 genotype on the concentrations of the azathioprine metabolites (also routine care for patients using these drugs); - To determine the transfer into breast milk.	—

Measure

Time frame

Secondary study parameters focus on the change of the fraction of tacrolimus/ciclosporin in plasma relative to whole blood before, during and after pregnancy. - Relating the free tacrolimus/ciclosporin and whole blood levels to kidney function. - Assessing whether there is a difference in the pharmacokinetics and pharmacodynamics of kidney transplant compared to liver transplant recipients. - To describe the pharmacokinetics of tacrolimus before, during and after pregnancy in kidney and liver transplant recipients in a population pharmacokinetic model using data from the concentration of whole blood tacrolimus, plasma tacrolimus, AUCs, the tacrolimus concentration within CD3+ T lymphocytes, genotyping of CYP3A, ABCB1 and POR, and body composition; - To perform simulations with the population pharmacokinetic model in order to predict which dosages of the drugs are needed to obtain the target trough concentration, for future pregnant patients after kidney of liver transplantation before, during and after pregnancy; - To define the correlation between whole-blood tacrolimus/ciclosporine concentrations and intracellular tacrolimus/ciclosporine concentrations and plasma tacrolimus/ciclosporin concentrations (prior to conception and during gestation); - To determine drug concentrations in umbilical cord blood and analyze the tacrolimus placenta transfer ratio; - To determine the effect of maternal CYP3A4 and CYP3A5 genotype and foetal CYP3A7 genotype on drug concentrations;-To determine the effect of maternal TPMT and NUDT15 genotype on the concentrations of the azathioprine metabolites (also routine care for patients using these drugs); - To determine the transfer into breast milk.

—

Countries

Netherlands

Contacts

Public ContactMFC Jong

Rijksuniversiteit Groningen

m.f.c.de.jong@umcg.nl+31503616161

Outcome results

None listed

Source: NL-OMON (via WHO ICTRP)