Mini Review
Volume 5 Issue 6 - 2021
Hepatic First Pass Metabolism: The Implication on the Biological Activity of Atypical Antipsychotic Agents
Chika J Mbah*
Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka, Enugu State, Nigeria
*Corresponding Author: Chika J Mbah, Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka, Enugu State, Nigeria.
Received: May 24, 2021; Published: May 31, 2021


Hepatic first pass metabolism is the metabolism of a drug in the liver received through the portal circulation prior to reaching systemic circulation. The liver is the principal organ of first pass metabolism in the body and has blood flow of about 20 - 25% of the total cardiac output. The objective of the study was to ascertain the effects of hepatic first pass metabolism on the biological activity of atypical antipsychotic agents. Scientific journals, official books and internet websites were the sources of the information. The results show amisulpride, aripiprazole, asenapine, cariprazine, clozapine, iloperidone, lurasidone, olanzapine, paliperidone, quetiapine, risperidone and ziprasidone to be the atypical antipsychotic agents. Some of them were found to undergo significant hepatic first pass metabolism. Poor bioavailability was observed with some of these atypical antipsychotics due to hepatic first pass metabolism. The therapeutic outcomes of orally administered atypical antipsychotic agents depict that there are relationships between threshold plasma drug levels and clinical responses. In summary, hepatic first pass metabolism has no drawbacks on the biological activity of clinically used atypical antipsychotic agents.

Keywords: Hepatic First Pass Metabolism; Atypical Antipsychotics; Biological Activity


  1. Sloss A. “Prescribing in liver disease”. Australia Prescriber2 (2009): 32-35.
  2. Vasanthkumar T., et al. “Hepatoprotective effect of curcumin and capsaicin against lipopolysaccharide induced liver damage in mice”. Pharmacognosy Journal6 (2017): 947-951.
  3. Derendorf H., et al. “Pharmacokinetics and oral bioavailability of hydrocortisone”. Journal Clinical Pharmacology 31 (1991): 473-476.
  4. Dresser GK., et al. “Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition”. Clinical Pharmacokinetic 38 (2000): 41-57.
  5. Reed MD., et al. “The single-dose pharmacokinetics of midazolam and its primary metabolite in pediatric patients after oral and intravenous administration”. Journal Clinical Pharmacology 12 (2001) 1359-1363.
  6. Kim J., et al. “Physicochemical properties and oral bioavailability of amorphous atorvastatin hemi-calcium using spray-drying and SAS process”. International Journal Pharmaceutics 1-2 (2008): 211-219.
  7. Antignac M., et al. “Population pharmacokinetics and bioavailability of tacrolimus in kidney transplant patients” British Journal Clinical Pharmacology6 (2007): 750-757.
  8. Sanders SW., et al. “Pharmacokinetics of ergotamine in healthy volunteers following oral and rectal dosing”. European Journal Clinical Pharmacology 3 (1986): 331-334.
  9. Shargel L and Yu AB. “Applied biopharmaceutics and pharmacokinetics”, 4th edition, McGraw-Hill, New York (1999).
  10. Leucht S., et al. “New generation antipsychotics versus low-potency conventional antipsychotics”: a systematic review and meta-analysis”. Lancet 361 (2003): 1581-1589.
  11. Bymaster FP., et al. “Radioreceptor binding profile of the atypical antipsychotic olanzapine”. Neuropsychopharmacology 14 (1996): 87-96.
  12. Mauri MC., et al. “Clinical pharmacology of atypical antipsychotics”: An update: EXCLI Journal 13 (2014): 1163-1191.
  13. Seeman P. “Atypical antipsychotics: mechanism of action”. Canadian Journal Psychiatry 47 (2002): 27-38.
  14. Miyamoto S., et al. “Treatments for schizophrenia: a critical review of pharmacology and mechanisms of action of antipsychotic drugs”. Molecular Psychiatry 10 (2005): 79-104.
  15. Horacek J., et al. “Mechanism of action of atypical antipsychotic drugs and the neurobiology of schizophrenia”. CNS Drugs 20 (2006): 389-409.
  16. Rosenzweig P., et al. “A review of the pharmacokinetics, tolerability and pharmacodynamics of amisulpride in healthy volunteers”. Human Psychopharmacology 17 (2002): 1-13.
  17. Jordan S., et al. “The antipsychotic aripiprazole is a potent, partial agonist at the human 5-HT1A receptor”. European Journal Pharmacology 441 (2002): 137-140.
  18. Winans E. “Aripiprazole”. American Journal Health System Pharmaceutics 60 (2003): 2437-2445.
  19. Citrome L. “Asenapine review, part I: chemistry, receptor affinity profile, pharmacokinetics and metabolism”. Expert Opinion on Drug Metabolism and Toxicology 10 (2014): 893-903.
  20. Jann MW., et al. “Pharmacokinetics and pharmacodynamics of clozapine”. Clinical Pharmacokinetic 24 (1993): 161-176.
  21. Rado JT and Janicak PG. “Long-term efficacy and safety of iloperidone: an update”. Neuropsychiatry Disposition Treatment 10 (2014): 409-415.
  22. Dinesh SP., et al. “LC–MS/MS assay for olanzapine in human plasma and its application to a bioequivalence study”. Acta Pharmaceutica Sinica B5 (2012): 481-494.
  23. Citrome L. “Oral paliperidone extended-release: chemistry, pharmacodynamics, pharmacokinetics and metabolism, clinical efficacy, safety and tolerability”. Expert Opinion on Drug Metabolism and Toxicology 8 (2012a): 873-888.
  24. Grimm SW., et al. “In vitro prediction of potential metabolic drug interaction for seroquel”. Schizophrenia Research 24 (1997): 198-201.
  25. Mannens G., et al. “Absorption, metabolism, and excretion of risperidone in humans”. Drug Metabolism Disposition 21 (1993): 1134-1141.
  26. Stimmel GL., et al. “Ziprasidone: an atypical antipsychotic drug for the treatment of schizophrenia”. Clinical Therapeutic 24 (2002): 21-37.
  27. Kronig MH., et al. “Plasma clozapine levels and clinical response for treatment-refractory schizophrenic patients”. American Journal Psychiatry 152 (1995): 179-182.
  28. Mauri MC., et al. “Clinical outcome and olanzapine plasma levels in acute schizophrenia”. European Psychiatry 20 (2005): 55-60.
  29. Khan AY and Preskorn SH. “Examining concentration dependence toxicity of clozapine: role of therapeutic drug monitoring”. Journal Psychiatry Practice 11 (2005): 289-301.
  30. Mauri MC., et al. “Clinical pharmacokinetics of atypical antipsychotics. A critical review of the relationship between plasma concentrations and clinical response”. Clinical Pharmacokinetic 46 (2007a): 359-388.
Citation: Chika J Mbah. “Hepatic First Pass Metabolism: The Implication on the Biological Activity of Atypical Antipsychotic Agents”. EC Emergency Medicine and Critical Care 5.6 (2021): 100-104.

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