Pregnancy‐related pharmacokinetic changes

@article{Tasnif2016PregnancyrelatedPC,
  title={Pregnancy‐related pharmacokinetic changes},
  author={Yasar Tasnif and Jacob Morado and MF Hebert},
  journal={Clinical Pharmacology \& Therapeutics},
  year={2016},
  volume={100}
}
The pharmacokinetics of many drugs are altered by pregnancy. Drug distribution and protein binding are changed by pregnancy. While some drug metabolizing enzymes have an apparent increase in activity, others have an apparent decrease in activity. Not only is drug metabolism affected by pregnancy, but renal filtration is also increased. In addition, pregnancy alters the apparent activities of multiple drug transporters resulting in changes in the net renal secretion of drugs. 
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References

SHOWING 1-10 OF 85 REFERENCES
Plasma Protein Binding of Drugs in Pregnancy and in Neonates
TLDR
Plasma composition and its effect on drug binding should be taken into account when prescribing highly protein bound drugs with narrow therapeutic: toxic ratios.
Induction of CYP2D6 in pregnancy
Valproic Acid Disposition and Protein Binding in Pregnancy
TLDR
Despite an upward dose adjustment in four patients, total valproic acid levels declined as pregnancy proceeded, but free levels did not, and Plasma free fractions and clearances increased, but intrinsic clearances remained unchanged.
Pregnancy‐induced changes in the pharmacokinetics of caffeine and its metabolites
TLDR
Significant decreases in caffeine metabolism and an increase in the active metabolite theophylline concentrations during pregnancy, especially in the third trimester are identified, revealing evidence of the large role that pregnancy plays in influencing caffeine metabolism.
Pharmacotherapy for Mood Disorders in Pregnancy: A Review of Pharmacokinetic Changes and Clinical Recommendations for Therapeutic Drug Monitoring
TLDR
Substantial pharmacokinetic changes can occur during pregnancy in a number of commonly used antidepressants and mood stabilizers, and close clinical monitoring of perinatal mood disorders and TDM of tricyclic antidepressants and Mood stabilizers are recommended.
Population pharmacokinetics of oseltamivir in non-pregnant and pregnant women.
TLDR
Based on the decrease in exposure of the active metabolite of oseltamivir carboxylate, the currently recommended doses of OS may need to be increased modestly in pregnant women in order to achieve comparable exposure with that of non-pregnant women.
Contributions of human cytochrome P450 enzymes to glyburide metabolism
TLDR
It was found that GLB could be depleted by all the enzymes tested; however, the intrinsic clearance of CYP3A4 for GLB depletion was 4–17 times greater than that of other CYP isoforms.
Safety and pharmacokinetics of etravirine in pregnant HIV‐1‐infected women *
TLDR
Etravirine is a next-generation NNRTI with demonstrated activity in treatment-experienced, HIV-1-infected adults and an assessment of available pharmacokinetic and safety data in pregnant women was undertaken.
Pharmacokinetics of metoprolol during pregnancy and lactation
TLDR
Clinicians who prescribe metoprolol during pregnancy should be prepared to make aggressive changes in dosage (dose and frequency) or consider using an alternate beta‐blocker.
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