Population pharmacokinetics and dosing simulations of amoxicillin in obese adults receiving co-amoxiclav

Abstract

Background Pneumonia, skin and soft tissue infections are more frequent in obese patients and are most often treated by co-amoxiclav, using similar dosing regimens to those used for non-obese subjects. No data are available on amoxicillin pharmacokinetics among obese subjects receiving co-amoxiclav. Materials and methods Prospective, single-centre, open-label, non-randomized, crossover pharmacokinetic trial having enrolled obese otherwise healthy adult subjects. A first dose of co-amoxiclav (amoxicillin/clavulanate 1000/200 mg) was infused IV over 30 min, followed by a second dose (1000/125 mg) administered orally, separated by a washout period of ≥24 h. We assayed concentrations of amoxicillin by a validated ultra HPLC–tandem MS technique. We estimated population pharmacokinetic parameters of amoxicillin by non-linear mixed-effect modelling using the SAEM algorithm developed by Monolix. Results Twenty-seven subjects were included in the IV study, with 24 included in the oral part of the study. Median body weight and BMI were 109.3 kg and 40.6 kg/m2, respectively. Amoxicillin pharmacokinetics were best described by a two-compartment model with first-order elimination. Mean values for clearance, central volume, intercompartmental clearance and peripheral volume were, respectively, 14.6 L/h, 9.0 L, 4.2 L/h and 6.4 L for amoxicillin. Oral bioavailability of amoxicillin was 79.7%. Amoxicillin Cmax after oral administration significantly reduced with weight (P = 0.013). Dosing simulations for amoxicillin predicted that most of the population will achieve the pharmacodynamic target of fT>MIC ≥40% with the regimen of co-amoxiclav 1000/200 mg (IV) or 1000/125 mg (oral) q8h for MICs titrated up to 0.5 mg/L (IV) and 1 mg/L (oral). Conclusions Pharmacokinetic/pharmacodynamic goals for amoxicillin can be obtained in obese subjects.

A Comparison of Pre-Emptive Co-Amoxiclav, Postoperative Amoxicillin, and Metronidazole for Prevention of Postoperative Complications in Dentoalveolar Surgery: A Randomized Controlled Trial

“…Co-amoxiclav (Augmentin) is a combination of clavulanic acid and amoxicillin [ 2 , 10 , 13 ]. The addition of clavulanic acid broadens the antibacterial spectrum of amoxicillin to include the bacteria which produce beta lactamase enzyme [ 1 , 2 , 3 , 4 , 5 , 6 ].…”

“…The co-amoxiclav used in this study is bactericidal instead of bacteriostatic. Oral administration of 625 mg co-amoxiclav requires 1.5 h to reach its peak blood concentration [ 10 ]. However, it may take up to 48 h of dosing for clinical improvement to appear [ 1 , 7 , 10 ].…”

“…Oral administration of 625 mg co-amoxiclav requires 1.5 h to reach its peak blood concentration [ 10 ]. However, it may take up to 48 h of dosing for clinical improvement to appear [ 1 , 7 , 10 ]. This means that giving a preventive dose of co-amoxiclav will make the extracted tooth socket a healthy and safe area for a blood clot to form.…”

“…Then, patients in all groups were post-medicated with co-amoxiclav (625 mg), amoxicillin (500 mg) or metronidazole (500 mg) plus 0.2% chlorhexidine mouthwash following the surgery for 5 days ( Figure 1 ). The co-amoxiclav, amoxicillin, and metronidazole doses used for this study were chosen according to manufacturer’s recommendation and set at such a level as to keep the minimum side effects [ 9 , 10 , 11 ]. Local anesthesia (1.8 mL mepivacaine 2% with epinephrine 1:100,000.)…”

The Effects of Bariatric Surgery and Gastrectomy on the Absorption of Drugs, Vitamins, and Mineral Elements

“…Mellon et al, observed that the amoxicillin C max decreased significantly with weight. Considering the target PK/PD value for beta-lactams fT > MIC ≥ 40%, the standard dosage of co-amoxiclav (1000/125 mg every 8 h) should be efficacious for obese adults [22], but Soares et al, suggested that amoxicillin treatment would fail if standard therapeutic regimens were applied because of a significantly higher volume of distribution in this group of patients [23].…”