The administration of oral probenecid with cephalexin was found to increase the probability of reaching the pharmacokinetic (PK) and pharmacodynamic (PD) targets of cephalexin, according to study results published in The Journal of Infection.
A crossover study was conducted to determine whether the co-administration of probenecid with cephalexin increases the probability of attaining the PK/PD targets of cephalexin compared with cephalexin alone. Overall, 11 healthy volunteers received oral cephalexin (1000 mg) after a standardized meal with or without oral probenecid (500 mg) on 2 separate days 1 week apart. Total plasma concentrations for both drugs were measured during a 12-hour period, and standard PK measures and contemporary PK/PD targets were compared.
In regard to cephalexin, the mean (95% CI) area under the concentration time curve increased 1.73-fold (1.61-1.85; P <.0001), peak plasma concentration increased 1.37-fold (1.16-1.58; P <.01), time to peak plasma concentration increased 1.45-fold (1.1-1.8; P <.01), and half-life increased 1.33-fold (1.03-1.62; P <.05) when coadministered with probenecid.
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According to the researchers, these results will lead to clinically meaningful increases in the probability of PK/PD target attainment. They provide an example whereby the PK/PD target attainment of the total concentrations above the minimum inhibitory concentration (8 mg/L) to inhibit methicillin-susceptible Staphylococcus aureus isolates for 70% of a 6-hour dose interval approached 100% for the cephalexin and probenecid combination compared with less than 15% for cephalexin alone.
The number of study participants was 1 fewer than recommended for Food and Drug Administration (FDA) bioequivalence studies. Further limitations included that the study was not fully blinded, the meal provided was smaller than FDA-approved meals for food-effect bioequivalence studies, and free cephalexin concentrations were not formally measured or estimated for simulations.
According to the researchers, “co-administration of probenecid extends the clinical application of oral cephalexin.” However, “clinical trials based on contemporary [PK/PD] knowledge are warranted,” the researchers concluded.
Reference
Everts RJ, Gardiner SJ, Zhang M, et al. Probenecid effects on cephalexin pharmacokinetics and pharmacodynamics in healthy volunteers. J Infect. 2021;83(2):182-189. doi: 10.1016/j.jinf.2021.05.037
This article originally appeared on Infectious Disease Advisor
