1. Pharmacokinetics of amoxicillin in obese and nonobese subjects
- Author
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Sérgio Seiji Yamada, Conrado de Souza Alcantara, Wendell Arthur Lopes, Cristina M. Kuroda, Josmar Mazucheli, Andréa Diniz, Sandra Regina Bin Silva, Caroline Ferraz Simões, Paulo Paixão, João Carlos Locatelli, Liane Maldaner, Ana Luiza Pelissari Peçanha de Paula Soares, Elza Kimura, Jesuí Vergílio Visentainer, Maiara Camotti Montanha, and Antonio Eduardo Nicácio
- Subjects
Adult ,medicine.medical_specialty ,Urology ,Cmax ,Administration, Oral ,Renal function ,030226 pharmacology & pharmacy ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Pharmacokinetics ,medicine ,Humans ,Pharmacology (medical) ,Obesity ,Prospective Studies ,030212 general & internal medicine ,Pharmacology ,Volume of distribution ,business.industry ,Area under the curve ,Amoxicillin ,medicine.disease ,Area Under Curve ,business ,Body mass index ,Chromatography, Liquid ,medicine.drug - Abstract
Aims To compare the pharmacokinetics of amoxicillin (AMX) in obese and nonobese subjects, given as single dose 875-mg tablets. Methods A prospective, single-centre, open-label, clinical study was carried out involving 10 nonobese and 20 obese subjects given a dose of an AMX 875-mg tablet. Serial blood samples were collected between 0 and 8 hours after administration of AMX and plasma levels were quantified by liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters (PK) were calculated by noncompartmental analysis and means of the 2 groups were compared using Student t-test. Analysis of correlation between covariates and PK was performed using Pearson's correlation coefficient. Results Ten nonobese subjects (mean age 30.6 ± 7.12 y; body mass index 21.56 ± 1.95 kg/m2 ) and 20 obese subjects (mean age 34.47 ± 7.03 y; body mass index 33.17 ± 2.38 kg/m2 ) participated in the study. Both maximum concentration (Cmax ; 12.12 ± 4.06 vs. 9.66 ± 2.93 mg/L) and area under the curve (AUC)0-inf (34.18 ± 12.94 mg.h/L vs. 26.88 ± 9.24 mg.h/L) were slightly higher in nonobese than in obese subjects, respectively, but differences were not significant. The volume of distribution (V/F) parameter was statistically significantly higher in obese compared to nonobese patients (44.20 ± 17.85 L vs. 27.57 ± 12.96 L). Statistically significant correlations were observed for several weight metrics vs. AUC, Cmax , V/F and clearance, and for creatinine clearance vs. AUC, Cmax and clearance. Conclusion In obese subjects, the main altered PK was V/F as a consequence of greater body weight. This may result in antibiotic treatment failure if standard therapeutic regimens are administered.
- Published
- 2021
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