Evaluation of various gentamicin dosage regimens in geriatric patients: a simulation study.
The aim of this simulation study was to evaluate the ability of three regimens proposed in official French recommendations for gentamicin to hit defined pharmacokinetic (PK) and pharmacodynamic targets in a population of elderly patients. The first drug regimen tested consisted of a loading dose of 1 mg/kg and a maintenance dose weighted by creatininemia, every 8 h. The second regimen consisted of a fixed dose of 1 mg/kg at various intervals of time, calculated from creatinine clearance. The last regimen was a fixed dose of 3 mg/kg once a day. All regimens were for 5 days. We used a bicompartmental PK model and implemented a Monte Carlo simulation to generate a large sample of geriatric subjects. The analysis examined three ranges of creatinine clearance. Simulations showed that for the two regimens using multiple doses per day, neither was able to reach an efficacy level without significant toxicity after 5 days of treatment, regardless of the level of renal function. The use of creatininemia or creatinine clearance to adjust the drug dose did not alter these findings. The once-a-day dosing regimen gave better results both in efficacy and toxicity, except for patients with creatinine clearance lower than 60 mL/min, where the incidence of potential toxicity was above 25%. These results strongly suggest that official French recommendations about aminoglycoside dosage regimens in elderly patients with renal impairment should be updated, and that the frequent need for therapeutic drug monitoring and dosage individualization should be clearly stated.
Bourguignon
Laurent
L
Université de Lyon, F-69000, Lyon, France.
Goutelle
Sylvain
S
De Saint-Martin
Julie Burdin
JB
Maire
Pascal
P
Ducher
Michel
M
D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D003198:Computer Simulation; D003404:Creatinine / Q000097:blood / Q000652:urine; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005839:Gentamicins / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D007677:Kidney Function Tests; D008954:Models, Biological; D009010:Monte Carlo Method; D017410:Practice Guidelines as Topic; D051437:Renal Insufficiency / Q000150:complications; D013997:Time Factors
D000900:Anti-Bacterial Agents; D005839:Gentamicins; D003404:Creatinine