Effect of aminophylline on the pharmacokinetics of amikacin in Sprague-Dawley rats

  • Seth Kwabena Amponsah Department of Pharmacology and Toxicology, School of Pharmacy, University of Ghana, Accra, Ghana
  • Kwabena Frimpong-Manso Opuni Department of Pharmaceutical Chemistry, School of Pharmacy, University of Ghana, Accra, Ghana
  • Kwabena Aboagye Antwi Department of Pharmacology and Toxicology, School of Pharmacy, University of Ghana, Accra, Ghana
  • Victor Pouzuing Kunkpeh Department of Pharmaceutical Chemistry, School of Pharmacy, University of Ghana, Accra, Ghana
Keywords: Excretion, Infection, Interaction, Pharmacokinetics

Abstract

Introduction: In most resource-poor settings, amikacin is normally co-administered with aminophylline among preterm newborns with infection and apnea of prematurity. There is the likelihood of an interaction between concurrently administered amikacin that is excreted almost solely via kidneys, and aminophylline, which is known to increase filtration fraction. The aim of this study was to evaluate the effect of aminophylline on the pharmacokinetics of amikacin using an animal model.

Methodology: Twelve male Sprague-Dawley rats (7 – 8 weeks old) were put into 2 equal groups. The test group received amikacin (10 mg/kg/day) with aminophylline (5 mg/kg/day) via the intraperitoneal route, and the control group received only amikacin (10 mg/kg/day) via the same route. On Day 4, after daily administration of drugs, tail vein blood samples were collected at different time points. Serum samples at each time point for each group were pooled and analyzed by fluorescence polarization immunoassay. Non-compartment pharmacokinetic analysis was used to estimate pharmacokinetic parameters. Area under the concentration-time curves (AUCs) were extrapolated from time 0 to infinity (AUC0→∞). Elimination rate constant (Ke) and elimination half-life (t1/2e) were also estimated.

Results: Pharmacokinetic parameters of the control group (amikacin only) vis-a-vis the test group were as follows: Cmax; 42.4 μmol/L vs 19.0 μmol/L, AUC0→∞; 84.9 μmol/L/h vs 41.4 μmol/L/h, Ke; 0.12 hours-1 vs 0.24 hours-1, and t1/2; 5.87 hours vs 2.88 hours, respectively.

Conclusion: This study suggests possible interaction between aminophylline and amikacin. However, further studies need to be conducted in humans to ascertain this finding.

Published
2019-03-31
How to Cite
1.
Amponsah SK, Opuni KF-M, Antwi KA, Kunkpeh VP (2019) Effect of aminophylline on the pharmacokinetics of amikacin in Sprague-Dawley rats. J Infect Dev Ctries 13:251-254. doi: 10.3855/jidc.10514
Section
Brief Original Articles