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[Comparative ototoxicity of aminoglycoside antibiotics in a guinea pig model (author's transl)]
Abstract:
Tobramycin, gentamicin, sisomicin and amikacin are aminoglycoside antibiotics that are used clinically. A significant side effect of aminoglycoside antibiotics is the production of hearing loss. Our study was done to determine the relative ototoxic liability of these 4 drugs. All drugs were given in daily doses of 0, 50,100 or 150 mg/kg to guinea pigs subcutaneously for 4 weeks. In addition, 200 mg/kg was was given to the animals receiving amikacin and sisomicin. There were 10 animals in each dosage group. Seven animals were used for auditory study and 3 were used for pharmacokinetic study. Auditory damage was assessed by determining the Preyer pinna reflex, the ability of the cochlea to generate the AC cochlear potential, and the number of sensory hair cells missing from the organ of Corti. The concentration of aminoglycoside antibiotics is determined in the cochlear perilymph and plasma by a radioenzymatic assay. On a equal dose basis the ototoxic liability of gentamicin and sisomicin were very similar and tobramycin and amikacin being less ototoxic than the gentamicin and sisomicin. The pharmacokinetics of single 150 mg/gk doses of the drugs were similar. The exception was that tobramycin reached lower peak levels in plasma and perilymph and its time to peak level in perilymph was delayed relative to the other drugs. Analysis of plasma and perilymph following chronic administration revealed higher concentration of gentamicin and sisomicin than of tobramycin and amikacin.
Insights
Gentamicin and sisomicin exhibit higher ototoxicity than tobramycin and amikacin, despite similar pharmacokinetics. This study compared the hearing loss potential of four clinical aminoglycoside antibiotics in guinea pigs.
Area of Science:
- Ototoxicology
- Pharmacology
- Auditory Science
Background:
- Aminoglycoside antibiotics (tobramycin, gentamicin, sisomicin, amikacin) are clinically vital but can cause hearing loss.
- Understanding the relative ototoxic liability of these drugs is crucial for patient safety.
Purpose of the Study:
- To compare the ototoxic potential of four commonly used aminoglycoside antibiotics.
- To evaluate the relationship between drug concentration in cochlear perilymph and plasma and auditory damage.
Main Methods:
- Guinea pigs received daily subcutaneous doses of 0-150 mg/kg of tobramycin, gentamicin, sisomicin, or amikacin for 4 weeks.
- Auditory function was assessed via Preyer pinna reflex, cochlear potential, and organ of Corti hair cell counts.
- Antibiotic concentrations in plasma and cochlear perilymph were measured using a radioenzymatic assay.
Main Results:
- Gentamicin and sisomicin demonstrated similar, higher ototoxicity compared to tobramycin and amikacin.
- Tobramycin showed delayed peak perilymph levels and lower concentrations in plasma and perilymph.
- Chronic administration revealed higher gentamicin and sisomicin concentrations in plasma and perilymph.
Conclusions:
- Gentamicin and sisomicin possess greater ototoxic liability than tobramycin and amikacin.
- Pharmacokinetic differences, particularly tobramycin's delayed perilymph uptake, may influence ototoxicity.
- These findings aid in selecting safer aminoglycoside antibiotic regimens.