title: Interspecies scaling of excretory amounts using allometry - retrospective analysis with rifapentine, aztreonam, carumonam, pefloxacin, miloxacin, trovafloxacin, doripenem, imipenem, cefozopran, ceftazidime, linezolid for urinary excretion and rifapentine, cabotegravir, and dolutegravir for fecal excretion.
abstract: 1. Interspecies allometry scaling for prediction of human excretory amounts in urine or feces was performed for numerous antibacterials. Antibacterials used for urinary scaling were: rifapentine, pefloxacin, trovafloxacin (Gr1/low; <10%); miloxacin, linezolid, PNU-142300 (Gr2/medium; 10-40%); aztreonam, carumonam, cefozopran, doripenem, imipenem, and ceftazidime (Gr3/high; >50%). Rifapentine, cabotegravir, and dolutegravir was used for fecal scaling (high; >50%). 2. The employment of allometry equation: Y = aW(b) enabled scaling of urine/fecal amounts from animal species. Corresponding predicted amounts were converted into % recovery by considering the respective human dose. Comparison of predicted/observed values enabled fold difference and error calculations (mean absolute error [MAE] and root mean square error [RMSE]). Comparisons were made for urinary/fecal data; and qualitative assessment was made amongst Gr1/Gr2/Gr3 for urine. 3. Average correlation coefficient for the allometry scaling was >0.995. Excretory amount predictions were largely within 0.75- to 1.5-fold differences. Average MAE and RMSE were within ±22% and 23%, respectively. Although robust predictions were achieved for higher urinary/fecal excretion (>50%), interspecies scaling was applicable for low/medium excretory drugs. 4. Based on the data, interspecies scaling of urine or fecal excretory amounts may be potentially used as a tool to understand the significance of either urinary or fecal routes of elimination in humans in early development.
authors.affiliation: a Department of Integrated Drug Development , Suramus Bio , Bangalore , Karnataka , India.
authors.forename: Nuggehally R
authors.initials: NR
authors.lastname: Srinivas
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000652:urine; D001398:Aztreonam / Q000031:analogs & derivatives / Q000378:metabolism; D015780:Carbapenems / Q000378:metabolism; D002442:Ceftazidime / Q000378:metabolism; D002511:Cephalosporins / Q000378:metabolism; D000077726:Doripenem; D005243:Feces / Q000737:chemistry; D024841:Fluoroquinolones / Q000378:metabolism; D006575:Heterocyclic Compounds, 3-Ring / Q000378:metabolism; D006801:Humans; D015378:Imipenem / Q000378:metabolism; D000069349:Linezolid / Q000378:metabolism; D009287:Naphthyridines / Q000378:metabolism; D010078:Oxazines; D010093:Oxolinic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D015366:Pefloxacin / Q000378:metabolism; D010879:Piperazines; D011728:Pyridones; D012189:Retrospective Studies; D012293:Rifampin / Q000031:analogs & derivatives / Q000378:metabolism; D000097586:Cefozopran; D000099226:Dolutegravir
chemical_list: D000900:Anti-Bacterial Agents; D001398:Aztreonam; D015780:Carbapenems; D002442:Ceftazidime; D002511:Cephalosporins; D000077726:Doripenem; D024841:Fluoroquinolones; D006575:Heterocyclic Compounds, 3-Ring; D015378:Imipenem; D000069349:Linezolid; D009287:Naphthyridines; D010078:Oxazines; D010093:Oxolinic Acid; D015366:Pefloxacin; D010879:Piperazines; D011728:Pyridones; D012293:Rifampin; D000097586:Cefozopran; D000099226:Dolutegravir; C044145:carumonam; C080163:trovafloxacin; C023981:miloxacin; C018421:rifapentine
keywords: Allometry; antibacterials; aztreonam; cabotegravir; excretion; feces; pharmacokinetics; urine