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Radionuclide Examination of the Kidneys
Published in Michael Ljungberg, Handbook of Nuclear Medicine and Molecular Imaging for Physicists, 2022
Clearance can be measured as plasma clearance, which is the volume of plasma cleared of the substance per unit time (not necessarily just by the kidneys), or renal clearance, which is the volume of plasma cleared per unit time by the kidneys (or cleared of the substance taken up by the kidneys). Urinary clearance is the volume of plasma cleared of the substance that is excreted into the urine. With the substances used to measure GFR, plasma, renal, and urinary clearances are equal because they are excreted exclusively by glomerular filtration in the kidneys and ultimately appear in the urine. The term plasma (instead of blood) clearance is used because the concentration of the test substance is usually measured in plasma. Whole blood (plasma plus blood cells) clearance is used less frequently. It can be the same as plasma clearance (with the substances entering blood cells) or greater than that, with the substances confined to plasma [19].
Antimicrobials in Pregnant Women
Published in Firza Alexander Gronthoud, Practical Clinical Microbiology and Infectious Diseases, 2020
Physiologic changes during pregnancy may lead to pharmacokinetic changes and impact antibiotic therapy. Pregnant women have decreased albumin. For highly protein-bound antibiotics, this means an increased volume of drug distribution and increased renal clearance. Further contributing to increased drug distribution is increased intravascular and extravascular volume. Increased renal clearance is further compounded by an increased glomerular filtration rate (GFR). Changes in gastrointestinal motility lead to reduced absorption and, consequently, reduced bioavailability of oral antibiotics.
Tubular Function
Published in Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal, Principles of Physiology for the Anaesthetist, 2020
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal
For any substance, renal clearance is the volume of plasma completely cleared of the substance by the kidneys per unit time. The units of renal clearance are therefore volume of plasma over time (e.g. mL/min or L/day).
Mirogabalin, a novel α2δ ligand, is not a substrate of LAT1, but of PEPT1, PEPT2, OAT1, OAT3, OCT2, MATE1 and MATE2-K
Published in Xenobiotica, 2022
Naotoshi Yamamura, Tsuyoshi Mikkaichi, Ken-ichi Itokawa, Misa Hoshi, Katja Damme, Stefanie Geigner, Christine Baumhauer
Urinary excretion of radioactivity in rats and monkeys after oral administration of [14C]mirogabalin at 3 mg/kg was 94.5 and 77.7%, respectively, and the radioactivity in the excreted urine in both animals included only mirogabalin without metabolites (Yamamura et al. 2022), thus urinary excretion amount of mirogabalin (Ae) was calculated as 3 mg/kg × 0.945 (= 2.835 mg/kg) for rats and 3 mg/kg × 0.777 (= 2.331 mg/kg) for monkeys. Pharmacokinetic parameters including plasma protein binding (fu) of mirogabalin in rats and monkeys after oral administration at 1, 3, and 10 mg/kg and intravenous administration at 3 mg/kg were also reported in the same literature (Yamamura et al. 2022). Renal clearance was calculated as Ae/AUCinf. Plasma unbound fraction (fu) was calculated as (100 – plasma protein binding ratio (%))/100. GFR was reported as 10.9 mL/min/kg of SD rats in the reference of Lin et al. 1987, as 3.06 mL/min/kg of cynomolgus monkeys in the reference of Iwama et al. 2014, and, as 94.6 mL/min/70 kg body weight of humans in the reference of Orlando et al. 1998. Renal filtration clearance of mirogabalin was calculated as GFR × fu. Apparent renal secretion clearance was calculated as renal clearance – GFR × fu, in case of no reabsorption happen. If renal reabsorption of mirogabalin happens, true renal secretion clearance must be bigger than apparent one.
Elucidation of clearance mechanism of TP0463518, a novel hypoxia-inducible factor prolyl hydroxylase inhibitor: does a species difference in excretion routes exist between humans and animals?
Published in Xenobiotica, 2022
Hiroki Takano, Akiko Mizuno-Yasuhira, Jun-ichi Yamaguchi, Hiromi Endo
The renal clearance of TP0463518 was estimated to be 3.6 L/h by multiplying the CL/F of 4.43 L/h by the urinary excretion rate of 80.7% in HV (Shinfuku et al. 2018). Therefore, the clearance via glomerular filtration was negligible, since the glomerular filtration clearance determined by multiplying the estimated glomerular filtration rate (eGFR) (88.85 mL/min/1.73 m2) in HV (Shinfuku et al. 2018) by the free fraction of TP0463518 in plasma (0.009) (Hamada et al. 2018) can only account for about 1% of the renal clearance. In addition, no metabolites were detected in plasma or urine in HD patients (Shinfuku et al. 2018). These results indicate that TP0463518 is predominantly cleared as unchanged TP0463518 by active renal excretion without metabolism in humans. In addition, the CL/F of 0.966–0.975 L/h in HD patients (Shinfuku et al. 2018) was 22% of that in HV, suggesting that a hepatic clearance mechanism also exists in humans, in addition to renal clearance.
Drug metabolic stability in early drug discovery to develop potential lead compounds
Published in Drug Metabolism Reviews, 2021
Siva Nageswara Rao Gajula, Nimisha Nadimpalli, Rajesh Sonti
Predicting in vivo pharmacokinetic data from the in vitro drug metabolism data is of great interest in preclinical studies. Data acquired from the in vitro metabolism helps in selecting potent leads for further development. Knowledge of drug clearance provides information about the dose required to maintain steady-state plasma concentration and drug disposition description (Chiou 1982; Bardal et al. 2011). Clearance is the volume of plasma from which the drug is removed per unit of time (Chiou 1982; Bardal et al. 2011). Plasma clearance (or total systemic clearance) can be characterized by all the metabolizing and eliminating organs involved in the drug clearance (Wilkinson and Shand 1975; Dowd 2017). These organs primarily include the liver (hepatic clearance) and kidney (renal clearance). Hepatic clearance is the liver's ability to remove the drug from the blood and is related to two variables: hepatic blood flow rate and intrinsic hepatic clearance (Wilkinson and Shand 1975). On the other hand, renal clearance is the volume of blood or plasma completely cleared off the drug by the kidneys per unit time (Tucker 1981).