Effects of altered plasma alpha-1-acid glycoprotein levels on pharmacokinetics of some basic antibiotics in pigs: simulation analysis

Journal of Veterinary Pharmacology and Therapeutics
Masanori KurohaM Shimoda

Abstract

Effects of altered plasma alpha-1-acid glycoprotein (AGP) levels on pharmacokinetic parameters of basic antimicrobials, erythromycin (EM), lincomycin (LM) and clindamycin (CM) were evaluated in pigs by simulation analysis. Intravenous (i.v.) injections of EM, LM and CM were performed to obtain pharmacokinetic parameters in healthy conditions. Binding parameters were obtained from an in vitro study using ultrafiltration. Simulation studies indicated that an increase of plasma AGP levels resulted in a decrease of both volume of distribution at steady state (Vdss) and total body clearance (Cltot) for all the drugs. Elimination rate constant for LM was almost unchanged by an increase of plasma AGP levels, whereas those for EM and CM were increased. Plasma concentration-time profiles at a high AGP level (often observed in pathophysiological conditions) were also simulated. All of the total plasma concentration-time profiles were different from those at normal AGP level. The differences were characterized by a higher initial concentration with faster or similar elimination. Unbound plasma concentration-time profile of LM was unaffected by AGP levels, whereas EM and CM were eliminated from plasma more rapidly at high AGP level. These ...Continue Reading

References

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Citations

Aug 25, 2007·American Journal of Respiratory and Critical Care Medicine·Momoyo AzumaSaburo Sone
Dec 3, 2011·Journal of Veterinary Pharmacology and Therapeutics·G A AlbarellosM F Landoni
Nov 20, 2003·Experimental Animals·Takashi KuribayashiShizuo Yamamoto
Oct 5, 2006·The Journal of Veterinary Medical Science·Kewei ZhangMinoru Shimoda
Oct 26, 2018·Research in Veterinary Science·Danielle A MzykRonald E Baynes

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