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Single-dose pharmacokinetics of isepamicin in young and geriatric volunteers
A A Nomeir1, E Radwanski, D Cutler
1Department of Drug Metabolism and Pharmacokinetics, Schering-Plough Research Institute, Kenilworth, New Jersey 07033, USA.
Insights
Isepamicin pharmacokinetics in adults show age-related changes, primarily due to renal function. Elderly individuals exhibit longer elimination half-life (t1/2 beta) and increased AUC0-infinity, indicating altered drug clearance.
Area of Science:
- Pharmacology
- Clinical Pharmacy
- Geriatric Medicine
Background:
- Isepamicin is a novel aminoglycoside antibiotic effective against Gram-negative and Gram-positive bacteria.
- Aminoglycosides require careful pharmacokinetic evaluation due to potential toxicity and variable patient responses.
Purpose of the Study:
- To assess the pharmacokinetics of isepamicin following intravenous infusion in young adult and geriatric volunteers.
- To determine the influence of age and renal function on isepamicin's pharmacokinetic profile.
Main Methods:
- Intravenous infusion of a 15 mg/kg dose of isepamicin over 0.5 hours.
- Pharmacokinetic parameters including elimination half-life (t1/2 beta), area under the plasma concentration-time curve (AUC0-infinity), systemic clearance (Cl), and renal clearance (Clr) were analyzed.
- Creatinine clearance (Clcr) was used to estimate renal function.
Main Results:
- Increased age correlated with higher t1/2 beta and AUC0-infinity, and lower Cl and Clr.
- Changes in systemic clearance were attributed to diminished renal function (Clcr).
- Maximum plasma concentration (Cmax), t1/2 tau, volume of distribution (Vdss), and 24-hour urinary excretion (Ae24 hrs) showed no significant age-related differences.
Conclusions:
- The altered pharmacokinetics of isepamicin in the elderly are primarily due to age-related decline in renal function, not age itself.
- Isepamicin demonstrated safety and tolerability in both young and geriatric populations.
- No gender-based pharmacokinetic differences were observed.
Abstract:
Isepamicin is a new aminoglycoside antibiotic with activity against both gram-negative and gram-positive bacteria. The pharmacokinetics of isepamicin were evaluated after a 0.5-hour intravenous infusion of alpha 15-mg/kg dose to groups of young adults and geriatric volunteers. Isepamicin was safe and well tolerated. No adverse events related to the infusion were reported. As age increased, there were increases in the elimination phase half-life (t1/2 beta) and the area under the plasma concentration-time curve extrapolated to infinity (AUC0-infinity), and decreases in systemic (Cl) and renal clearance (Clr). The changes seen in Cl with age were a result of changes in renal function estimated by creatinine clearance (Clcr). There were no apparent correlations between age and maximum plasma concentration (Cmax), half-life of the tau-phase (t1/2 tau), volume of distribution at steady-state (Vdss), or the amount of isepamicin excreted in urine within 24 hours after dose administration (Ae24 hrs). When comparing the elderly (61-80 years old) with the younger (21-60 years) volunteers, the (AUC0-infinity), and t1/2 beta values were higher in the elderly and the Cl and Clr values were lower, but Cmax, t1/2 tau and Vdss were similar in the two age groups. The contribution of the tau-phase to the overall AUC was minimal and similar for the two age groups. Also, there were no gender effects on the pharmacokinetics of isepamicin in both the young and elderly volunteers. These results demonstrate that changes in the pharmacokinetics of isepamicin in the elderly are attributable to changes in renal function, whereas age, per se, is not a significant factor.