Interspecies scaling of urinary excretory amounts of nine drugs belonging to different therapeutic areas with diverse chemical structures - accurate prediction of the human urinary excretory amounts.
1. The human urinary excretory amounts of total drug (parent + metabolites) were predicted for nine drugs with diverse chemical structures using simple allometry. The drugs used for scaling were cephapirin, olanzapine, labetolol, carisbamate, voriconazole, tofacitinib, nevirapine, ropinirole, and cyclindole. 2. The traditional allometric scaling was attempted using Y = aWbrelationship. The corresponding predicted urinary amounts were converted into % recovery by using appropriate human dose. Appropriate statistical tests comprising of fold-difference (predicted/observed values) and error calculations (MAE and RMSE) were performed. 3. The interspecies scaling of all nine drugs tested showed excellent correlation (r > 0.9672). The predictions for eight out of nine drugs (exception was cephaphirin) were contained within 0.80-1.25 fold-differences. The MAE and RMSE were within ± 18% and 14.64%, respectively. 4. The present work supported the potential application of prospective allometry scaling to predict the urinary excretory amounts of the total drug and gauge any issues for the renal handling of the total drug.
a Drug Metabolism and Pharmacokinetics, Jubilant Biosys Ltd , Industrial Suburb, Yeshwanthpur, Bangalore , India and.
Ravi Kanth
RK
Bhamidipati
a Drug Metabolism and Pharmacokinetics, Jubilant Biosys Ltd , Industrial Suburb, Yeshwanthpur, Bangalore , India and.
Ramesh
R
Mullangi
b DRILS , Gachibowli , Hyderabad , India.
Nuggehally R
NR
Srinivas
D000818:Animals; D001569:Benzodiazepines / Q000652:urine; D002219:Carbamates / Q000652:urine; D002227:Carbazoles / Q000652:urine; D002514:Cephapirin / Q000652:urine; D006801:Humans; D007211:Indoles / Q000652:urine; D007741:Labetalol / Q000652:urine; D019829:Nevirapine / Q000652:urine; D000077152:Olanzapine; D004364:Pharmaceutical Preparations / Q000652:urine*; D010880:Piperidines / Q000652:urine; D011446:Prospective Studies; D011743:Pyrimidines / Q000652:urine; D011758:Pyrroles / Q000652:urine; D013045:Species Specificity; D065819:Voriconazole / Q000652:urine
D002219:Carbamates; D002227:Carbazoles; D007211:Indoles; D004364:Pharmaceutical Preparations; D010880:Piperidines; D011743:Pyrimidines; D011758:Pyrroles; C518914:S-2-O-carbamoyl-1-o-chlorophenyl-ethanol; C046649:ropinirole; D001569:Benzodiazepines; C479163:tofacitinib; D002514:Cephapirin; D019829:Nevirapine; C014432:cyclindole; D065819:Voriconazole; D000077152:Olanzapine; D007741:Labetalol
Allometry; excretion; pharmacokinetics; urine