Simultaneous measurement of glomerular filtration rate, effective renal plasma flow and tubular secretion in different poultry species by single intravenous bolus of iohexol and para-aminohippuric acid

Simple Summary The aim of this study was to investigate the simultaneous measurement of two different renal markers (iohexol and p-aminohippuric acid) in the plasma of different poultry species as the gold standard method. The two markers reflect three different renal processes: glomerular filtration, effective renal plasma flow, and tubular secretion. The rate at which the kidneys filter blood is called the glomerular filtration rate. The effective renal plasma flow is the volume of plasma that reaches the kidney per time unit. Tubular secretion can be defined as active transport from the peritubular capillaries to the renal tubules. A moderate correlation was observed between tubular secretion and the glomerular filtration rate. A good correlation was demonstrated between the effective renal plasma flow and the glomerular filtration rate. This might be useful to model both renal processes. This approach could support the further development and validation of clinical renal biomarkers. These markers can be useful in the case of a chronic renal disease or renal failure, for which repeated evaluations of the renal function are required. The aim of the current study was to investigate the simultaneous measurement of plasma p-aminohippuric acid (PAH) clearance as a potential marker to assess effective renal plasma flow (eRPF) and tubular secretion (TS), and the plasma clearance of iohexol (IOH) as a marker of the glomerular filtration rate in poultry species. The PAH was administered intravenously (IV) to broiler chickens, layers, turkeys, Muscovy ducks, and pigeons. Each animal received successively a single bolus dose of 10 mg PAH/kg bodyweight (BW) and 100 mg PAH/kg BW to assess the eRPF and TS, respectively. Simultaneously with both PAH administrations, a single IV bolus of 64.7 mg/kg BW of IOH was administered. A high linear correlation (R-2= 0.79) between eRPF, based on the clearance of the low dose of PAH, and BW was observed for the poultry species. The correlation between TS, based on the clearance of the high dose of PAH, and BW was moderate (R-2= 0.50). Finally, a moderate correlation (R-2= 0.68) was demonstrated between GFR and eRPF and between GFR and TS (R-2= 0.56). This presented pharmacokinetic approach of the simultaneous administration of IOH and PAH enabled a simultaneous evaluation of eRPF/TS and GFR, respectively, in different poultry species

Enantiomer specific pharmacokinetics of ibuprofen in preterm neonates with patent ductus arteriosus

Aims: Racemic ibuprofen is widely used for the treatment of preterm neonates with patent ductus arteriosus. Currently used bodyweight-based dosing guidelines are based on total ibuprofen, while only the S-enantiomer of ibuprofen is pharmacologically active. We aimed to optimize ibuprofen dosing for preterm neonates of different ages based on an enantiomer-specific population pharmacokinetic model. Methods: We prospectively collected 210 plasma samples of 67 preterm neonates treated with ibuprofen for patent ductus arteriosus (median gestational age [GA] 26 [range 24–30] weeks, median body weight 0.83 [0.45–1.59] kg, median postnatal age [PNA] 3 [1–12] days), and developed a population pharmacokinetic model for S- and R-ibuprofen. Results: We found that S-ibuprofen clearance (CLS, 3.98 mL/h [relative standard error {RSE} 8%]) increases with PNA and GA, with exponents of 2.25 (RSE 6%) and 5.81 (RSE 15%), respectively. Additionally, a 3.11-fold higher CLS was estimated for preterm neonates born small for GA (RSE 34%). Clearance of R-ibuprofen was found to be high compared to CLS (18 mL/h [RSE 24%]), resulting in a low contribution of R-ibuprofen to total ibuprofen exposure. Current body weight was identified as covariate on both volume of distribution of S-ibuprofen and R-ibuprofen. Conclusion: S-ibuprofen clearance shows important maturation, especially with PNA, resulting in an up to 3-fold increase in CLS during a 3-day treatment regimen. This rapid increase in clearance needs to be incorporated in dosing guidelines by adjusting the dose for every day after birth to achieve equal ibuprofen exposure