Tags

Type your tag names separated by a space and hit enter

Hepatic pharmacokinetics of propranolol in rats with adjuvant-induced systemic inflammation.
Am J Physiol Gastrointest Liver Physiol. 2006 Feb; 290(2):G343-51.AJ

Abstract

Systemic inflammation is known to affect drug disposition in the liver. This study sought to relate and quantitate changes in hepatic pharmacokinetics of propranolol with changes in hepatic architecture and physiology in adjuvant-treated rats. Transmission electron microscopy was used to assess morphological changes in mitochondria and lysosomes of adjuvant-treated rat livers. The disposition of propranolol was assessed in the perfused rat liver using the multiple indicator dilution technique. Hepatic extraction and mean transit time were determined from outflow-concentration profiles using a nonparametric method. Kinetic parameters were derived from a two-phase physiologically based organ pharmacokinetic model. Possible relationships were then explored between the changes in hepatic drug disposition and cytochrome P-450 activity and iron concentration. Adjuvant treatment induced the appearance of mitochondrial inclusions/tubularization and irregularly shaped lysosomes in rat livers. Livers from adjuvant-treated rats had (relative to normal) significantly higher alpha(1)-acid glycoprotein (orosomucoid) and iron tissue concentrations but lower cytochrome P-450 content. The hepatic extraction, metabolism, and ion trapping of propranolol were significantly impaired in adjuvant-treated rats and could be correlated with altered iron store and cytochrome P-450 activity. It is concluded that adjuvant-induced systemic inflammation alters hepatocellular morphology and biochemistry and consequently influences hepatic disposition of propranolol.

Authors+Show Affiliations

Department of Medicine, University of Queensland, Princess Alexandra Hospital, Woollongabba, Queensland 4102, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16166348

Citation

Hung, Daniel Y., et al. "Hepatic Pharmacokinetics of Propranolol in Rats With Adjuvant-induced Systemic Inflammation." American Journal of Physiology. Gastrointestinal and Liver Physiology, vol. 290, no. 2, 2006, pp. G343-51.
Hung DY, Siebert GA, Chang P, et al. Hepatic pharmacokinetics of propranolol in rats with adjuvant-induced systemic inflammation. Am J Physiol Gastrointest Liver Physiol. 2006;290(2):G343-51.
Hung, D. Y., Siebert, G. A., Chang, P., Whitehouse, M. W., Fletcher, L., Crawford, D. H., & Roberts, M. S. (2006). Hepatic pharmacokinetics of propranolol in rats with adjuvant-induced systemic inflammation. American Journal of Physiology. Gastrointestinal and Liver Physiology, 290(2), G343-51.
Hung DY, et al. Hepatic Pharmacokinetics of Propranolol in Rats With Adjuvant-induced Systemic Inflammation. Am J Physiol Gastrointest Liver Physiol. 2006;290(2):G343-51. PubMed PMID: 16166348.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hepatic pharmacokinetics of propranolol in rats with adjuvant-induced systemic inflammation. AU - Hung,Daniel Y, AU - Siebert,Gerhard A, AU - Chang,Ping, AU - Whitehouse,Michael W, AU - Fletcher,Linda, AU - Crawford,Darrell H G, AU - Roberts,Michael S, Y1 - 2005/09/15/ PY - 2005/9/17/pubmed PY - 2006/3/3/medline PY - 2005/9/17/entrez SP - G343 EP - 51 JF - American journal of physiology. Gastrointestinal and liver physiology JO - Am J Physiol Gastrointest Liver Physiol VL - 290 IS - 2 N2 - Systemic inflammation is known to affect drug disposition in the liver. This study sought to relate and quantitate changes in hepatic pharmacokinetics of propranolol with changes in hepatic architecture and physiology in adjuvant-treated rats. Transmission electron microscopy was used to assess morphological changes in mitochondria and lysosomes of adjuvant-treated rat livers. The disposition of propranolol was assessed in the perfused rat liver using the multiple indicator dilution technique. Hepatic extraction and mean transit time were determined from outflow-concentration profiles using a nonparametric method. Kinetic parameters were derived from a two-phase physiologically based organ pharmacokinetic model. Possible relationships were then explored between the changes in hepatic drug disposition and cytochrome P-450 activity and iron concentration. Adjuvant treatment induced the appearance of mitochondrial inclusions/tubularization and irregularly shaped lysosomes in rat livers. Livers from adjuvant-treated rats had (relative to normal) significantly higher alpha(1)-acid glycoprotein (orosomucoid) and iron tissue concentrations but lower cytochrome P-450 content. The hepatic extraction, metabolism, and ion trapping of propranolol were significantly impaired in adjuvant-treated rats and could be correlated with altered iron store and cytochrome P-450 activity. It is concluded that adjuvant-induced systemic inflammation alters hepatocellular morphology and biochemistry and consequently influences hepatic disposition of propranolol. SN - 0193-1857 UR - https://www.unboundmedicine.com/medline/citation/16166348/Hepatic_pharmacokinetics_of_propranolol_in_rats_with_adjuvant_induced_systemic_inflammation_ L2 - https://journals.physiology.org/doi/10.1152/ajpgi.00155.2005?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -