scholarly journals Metabolism, Excretion, and Mass Balance of [ 14 C]-Rezafungin in Animals and Humans

2021 ◽  
Author(s):  
Voon Ong ◽  
Sarah Wills ◽  
Deborah Watson ◽  
Taylor Sandison ◽  
Shawn Flanagan
Keyword(s):  
Mass Balance ◽  
Parent Drug ◽  
Invasive Fungal Disease ◽  
Total Radioactivity ◽  
Fecal Excretion ◽  
Total Recovery ◽  
Clinical Pharmacokinetics ◽  
Blood And Marrow Transplantation ◽  
Clinical Observations ◽  
Major Route

Rezafungin is a novel echinocandin being developed for treatment of candidemia and invasive candidiasis and for prevention of invasive fungal disease caused by Candida , Aspergillus , and Pneumocystis spp. in recipients of blood and marrow transplantation. Studies using [ 14 C]-radiolabeled rezafungin were conducted in rats, monkeys, and humans to characterize the mass balance, excretion, and pharmacokinetics of [ 14 C]-rezafungin and to evaluate relative amounts of rezafungin metabolites compared with parent drug. Fecal excretion was the main route of elimination in rats, monkeys, and humans. Radioactivity was primarily excreted as unchanged drug, with ≥95% average total recovery in rats (through 336 hours) and monkeys (through 720 hours). In humans, cumulative recovery of radioactivity through the first 17 days was 52% (38% in feces, 14% in urine) with estimated mean overall recovery through Day 60 of 88.3% (73% in feces, 27% in urine). The clinical pharmacokinetics of rezafungin following a single 400-mg intravenous infusion (200 μCi of [ 14 C]-rezafungin) were similar in plasma, plasma total radioactivity, and whole blood total radioactivity. Unchanged rezafungin represented the majority of total radioactivity in plasma, and the partitioning of total radioactivity into red blood cells was negligible. Across species, rezafungin was primarily metabolized by hydroxylation of the terphenyl, pentyl ether side chain. In these excretion/mass balance, metabolism, and PK studies, clinical observations were consistent with findings in the rat and monkey demonstrating the minimal metabolism and slow elimination of rezafungin after intravenous administration, with fecal excretion as the major route of elimination.

scholarly journals 1286. Pharmacokinetics, Excretion, and Mass Balance of [14C]-Rezafungin Following Intravenous (IV) Administration in Healthy Adults

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S658-S659
Author(s):  
Voon Ong ◽  
Shawn Flanagan ◽  
Taylor Sandison ◽  
Sarah Wills
Keyword(s):  
Invasive Fungal Disease ◽  
Linear Interpolation ◽  
Marrow Transplant ◽  
Research Unit ◽  
Total Radioactivity ◽  
Fecal Excretion ◽  
Blood And Marrow Transplant ◽  
Clinical Research Unit ◽  
Major Route ◽  
A Minor

Abstract Background Rezafungin is a once-weekly novel echinocandin antifungal currently in Phase 3 development for treatment of candidemia and invasive candidiasis (ReSTORE) and for prevention of invasive fungal disease caused by Candida, Aspergillus, and Pneumocystis in blood and marrow transplant recipients (ReSPECT). Nonclinical ADME studies in rats and monkeys show rezafungin is primarily excreted unchanged in feces, with urine as a minor route. This study was conducted to characterize the routes of elimination of [14C]-rezafungin and the pharmacokinetics of total radioactivity and plasma rezafungin in humans. Methods Nine healthy male subjects received a single IV 400-mg rezafungin infusion containing 200 µCi of [14C]-rezafungin. Serial blood samples, urine, and feces were collected at specified times over 60 days; subjects were initially confined in the clinical research unit (CRU) for 17 days postdose and returned for two follow-up visits (days 29 and 60). During the period of time subjects were away from the CRU, recovery of radioactivity was estimated by linear interpolation. Results Rezafungin exhibited a long plasma half-life and was mainly excreted in feces unchanged. Cumulative recovery of radioactivity from excreta collected through the first 17 days was 52% (38% in feces, 14% in urine), reinforcing the slow overall elimination of rezafungin. Overall recovery of the administered dose by day 60 was estimated to be 88.3% (65.6% in feces, 22.7% in urine) (Figure 1). Mean blood/plasma concentration ratios ranged from 0.860 to 1.02 through the last collection time point (day 60), which indicated low association of radioactivity with blood cells. Rezafungin was the predominant compound measured in plasma and feces across all collected time points. In the urine, as observed in rat and monkey metabolite profiling studies, low level, inactive, oxidative metabolites were identified as 2-, 3-, 4-hydroxylpentyl rezafungin, and despentyl-rezafungin Figure 1 Conclusion Results from this human excretion balance, metabolism and PK study are consistent with nonclinical results, which showed fecal excretion as the major route of elimination of rezafungin. Rezafungin was the predominant compound in plasma and feces. Disclosures Voon Ong, PhD, Cidara Therapeutics, Inc. (Employee, Shareholder) Shawn Flanagan, PhD, Cidara Therapeutics, Inc. (Employee, Shareholder) Taylor Sandison, MD, MPH, Cidara Therapeutics, Inc. (Employee, Shareholder)

Absorption, Metabolism and Excretion of Surufatinib in Rats and Humans

2020 ◽  
Vol 21 (5) ◽  
pp. 357-367
Author(s):  
Ke Li ◽  
Sheng Ma ◽  
Liyan Miao ◽  
Songhua Fan ◽  
Bin Pan ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Parent Drug ◽  
Total Radioactivity ◽  
Female Rats ◽  
Male Rats ◽  
Fecal Excretion ◽  
Post Dose ◽  
Human Volunteers ◽  
Significant Efficacy ◽  
A Minor

Background: Surufatinib is a potent small-molecule tyrosine kinase inhibitor and exhibited significant efficacy in the treatment of neuroendocrine tumors in clinical trials. Objective: The absorption, metabolism and excretion of surufatinib were investigated in rats and human volunteers following a single oral dose of [14C] surufatinib. Methods: The radioactivity was measured in plasma, urine, feces and bile by liquid scintillation counting, and the metabolites were characterized by liquid chromatography coupled to mass spectrometry. Results: Surufatinib was orally absorbed similarly in rats and human volunteers, with the median Tmax of 4 hours post-dose. The estimated t1/2 appeared longer in humans than in rats (mean t1/2: 3.12 hour for male rats, 6.48 hours for female rats and 23.3 hours for male human volunteers). The excretion of surufatinib was almost complete in rats and human volunteers in the studies, with the total radioactivity recovery of >90% of the dose. Similarly, in rats and humans, fecal excretion predominated (approximately 87% of the dose recovered in feces and only 5% in urine). The parent drug was the major radioactive component detected in the plasma extracts of rats and humans, and no single circulating metabolite accounted for >10% of the total radioactivity. Unchanged drug was a minor radioactive component in the excreta of rats and humans. Conclusion: Fecal excretion was the predominant way for the elimination of surufatinib and its metabolites in rats and humans. No disproportionate circulating metabolite was observed in humans.

scholarly journals Mass Balance and Pharmacokinetics of [14C]Telavancin following Intravenous Administration to Healthy Male Volunteers

2010 ◽  
Vol 54 (8) ◽  
pp. 3365-3371 ◽  
Author(s):  
Jeng-Pyng Shaw ◽  
Jonathan Cheong ◽  
Michael R. Goldberg ◽  
Michael M. Kitt
Keyword(s):  
Mass Balance ◽  
Whole Blood ◽  
Phase 1 ◽  
Parent Drug ◽  
Study Drug ◽  
Total Radioactivity ◽  
Healthy Male ◽  
Open Label ◽  
Study Drug Administration ◽  
Open Label Phase

ABSTRACT The mass balance and pharmacokinetics of telavancin, a semisynthetic lipoglycopeptide antimicrobial agent, were characterized in an open-label, phase 1 study of six healthy male subjects. After a single 1-h intravenous infusion of 10 mg/kg [14C]telavancin (0.68 μCi/kg), blood, urine, and feces were collected at regular intervals up to 216 h postdose. Whole blood, plasma, urine, and fecal samples were assayed for total radioactivity using scintillation counting; plasma and urine were also assayed for parent drug and metabolites using liquid chromatography with tandem mass spectrometry. The concentration-time profiles for telavancin and total radioactivity in plasma were comparable from 0 to 24 h after the study drug administration. Telavancin accounted for >95% and 83% of total radioactivity in plasma at 12 h and 24 h, respectively. By 216 h, approximately 76% of the total administered dose was recovered in urine while only 1% was collected in feces. Unchanged telavancin accounted for most (83%) of the eliminated dose. Telavancin metabolite THRX-651540 along with two other hydroxylated metabolites (designated M1 and M2) accounted for the remaining radioactivity recovered from urine. The mean concentrations of total radioactivity in whole blood were lower than the concentration observed in plasma, and mean concentrations of THRX-651540 in plasma were minimal relative to mean plasma telavancin concentrations. These observations demonstrate that most of an administered telavancin dose is eliminated unchanged via the kidneys. Intravenous telavancin at 10 mg/kg was well tolerated by all subjects.

ENHANCEMENT OF SCREEN FILM MAMMOGRAM UP TO A LEVEL OF DIGITAL MAMMOGRAM: EXPERIMENTAL ANALYSIS

2013 ◽  
Vol 13 (02) ◽  
pp. 1340004
Author(s):  
APARNA NARENDRA BHALE ◽  
MANISH RATNAKAR JOSHI
Keyword(s):  
Experimental Analysis ◽  
Breast Imaging ◽  
Point Of View ◽  
Quality Analysis ◽  
Digital Mammogram ◽  
Total Recovery ◽  
Clinical Observations ◽  
Opinion Score ◽  
Better Than

Breast cancer is one of the major causes of death among women. If a cancer can be detected early, the options of treatment and the chances of total recovery will increase. From a woman's point of view, the procedure practiced (compression of breasts to record an image) to obtain a digital mammogram (DM) is exactly the same that is used to obtain a screen film mammogram (SFM). The quality of DM is undoubtedly better than SFM. However, obtaining DM is costlier and very few institutions can afford DM machines. According to the National Cancer Institute 92% of breast imaging centers in India do not have digital mammography machines and they depend on the conventional SFM. Hence in this context, one should answer "Can SFM be enhanced up to a level of DM?" In this paper, we discuss our experimental analysis in this regard. We applied elementary image enhancement techniques to obtain enhanced SFM. We performed the quality analysis of DM and enhanced SFM using standard metrics like PSNR and RMSE on more than 350 mammograms. We also used mean opinion score (MOS) analysis to evaluate enhanced SFMs. The results showed that the clarity of processed SFM is as good as DM. Furthermore, we analyzed the extent of radiation exposed during SFM and DM. We presented our literally findings and clinical observations.

scholarly journals Disposition of Posaconazole following Single-Dose Oral Administration in Healthy Subjects

2004 ◽  
Vol 48 (9) ◽  
pp. 3543-3551 ◽  
Author(s):  
Philip Krieter ◽  
Brian Flannery ◽  
Timothy Musick ◽  
Mark Gohdes ◽  
Monika Martinho ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Fungal Infections ◽  
Phase 1 ◽  
Parent Drug ◽  
Total Radioactivity ◽  
Plasma And Urine Samples ◽  
Dose Oral ◽  
Orally Bioavailable ◽  
A Minor ◽  
Male Subjects

ABSTRACT Posaconazole is a potent, broad-spectrum triazole antifungal agent currently in clinical development for the treatment of refractory invasive fungal infections. Eight healthy male subjects received a single 399-mg (81.7 μCi) oral dose of [14C]posaconazole after consuming a high-fat breakfast. Urine, feces, and blood samples were collected for up to 336 h postdose and assayed for total radioactivity; plasma and urine samples were also assayed for parent drug. Posaconazole was orally bioavailable, with a median maximum posaconazole concentration in plasma achieved by 10 h postdose. Thereafter, posaconazole was slowly eliminated, with a mean half-life of 20 h. The greatest peak in the radioactivity profile of pooled plasma extracts was due to posaconazole, with smaller peaks due to a monoglucuronide, a diglucuronide, and a smaller fragment of the molecule. The mean total amount of radioactivity recovered was 91.1%; the cumulative excretion of radioactivity in feces and in urine was 76.9 and 14.0% of the dose, respectively. Most of the fecal radioactivity was associated with posaconazole, which accounted for 66.3% of the administered dose; however, urine contained only trace amounts of unchanged posaconazole. The radioactivity profile of pooled urine extracts included two monoglucuronide conjugates and a diglucuronide conjugate of posaconazole. These observations suggest that oxidative (phase 1) metabolism by cytochrome P450 isoforms represents only a minor route of elimination for posaconazole, and therefore cytochrome P450-mediated drug interactions should have a limited potential to impact posaconazole pharmacokinetics.

Fecal Nickel Excretion by Healthy Adults

1973 ◽  
Vol 19 (4) ◽  
pp. 429-430 ◽  
Author(s):  
Eva Horak ◽  
F William Sunderman
Keyword(s):  
Occupational Exposure ◽  
Occupational Exposures ◽  
Absorption Spectrometry ◽  
Dry Weight ◽  
Weight Basis ◽  
Fecal Excretion ◽  
Hospital Workers ◽  
Major Route ◽  
Wet Weight ◽  
Comprehensive Evaluations

Abstract Nickel was measured by atomic absorption spectrometry in three-day collections of feces from healthy hospital workers (age 22-65) who had lived for more than a year in Hartford, Connecticut. None of the 10 subjects (4/♂ , 6/♀.) had occupational exposure to nickel. Fecal nickel averaged 3.3 µg/g (wet weight); SD, ±0.8; and range, 2.1 to 4.4 µg/g. Corresponding figures on a dry-weight basis were 14.2 µg/g; SD, ±2.7; and range, 10.8 to 18.7 µg/g. The fecal excretion of nickel averaged 258 µg/day (SD, ±126; range, 80 to 540 µg/day). Fecal excretion is evidently the major route for elimination of nickel from the human body. Comprehensive evaluations of environmental or occupational exposures to nickel should also include analyses of nickel in serum, urine, and hair.

Metabolism and Disposition of Betrixaban and Its Lack of Interaction with Major CYP Enzymes.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2266-2266 ◽  
Author(s):  
Athiwat Hutchaleelaha ◽  
Christine Ye ◽  
Yonghong Song ◽  
Todd Lorenz ◽  
Daniel Gretler ◽  
...  
Keyword(s):  
Mass Balance ◽  
Human Plasma ◽  
Half Life ◽  
Total Radioactivity ◽  
Time Dependent ◽  
Post Dose ◽  
Cyp Enzymes ◽  
Dependent Inhibition ◽  
Cyp Inhibition ◽  
Time Dependent Inhibition

Abstract Abstract 2266 Betrixaban is a once daily oral Factor Xa inhibitor being investigated in a Phase 3 clinical trial to prevent venous thromboembolism in acute medically ill patients (APEX Study). Mass balance, metabolite profile and interaction with major CYP enzymes were evaluated in this study. Portola study 06–005 was an open-label, single-dose, mass-balance and metabolic profiling study using 14C-labeled betrixaban in 5 healthy male volunteers. Each subject received a single oral solution containing 40 mg of betrixaban labeled with 100 μCi of 14C. Blood samples were taken serially over a 168-hour interval. Urine samples and fecal samples were collected during the 7–14 day confinement period. Subjects were discharged from the unit when at least one of the following criteria were met: 90% of the radioactivity was recovered in urine and feces, daily excreted radioactivity was 1% or less of administered dose on two consecutive days, or subject reached 336 hours (14 days) post dose. The plasma concentration equivalents of total radioactivity increased rapidly following dosing with a mean peak of 31.69 ng eq/mL occurring at 3.5 hours post-dose. AUC and half-life could not be calculated as radioactivity in plasma could only be detected up to 6 hours post dose. Terminal elimination half life determined in other clinical pharmacology studies was 37 hours. Total radioactivity recovered from urine and feces was approximately 96% (range 92% to 99%), with the majority of 14C recovery in feces (82% to 89% of the dose). The 14C dose recovered in urine, composed of betrixaban and inactive metabolites, ranged from 6% to 13%. The metabolic profile of betrixaban was determined in plasma, urine and feces. Unchanged betrixaban was the predominant component found in human plasma and excreta, accounting for 85.3% of the dose excreted in urine and feces. The major biotransformation pathway for betrixaban was hydrolysis to form PRT062802 and PRT062803, a non-14C labeled metabolite (Figure 1). PRT062803 can be demethylated to form PRT062799 or hydroxylated to form PRT062982. PRT062982 is further conjugated with sulfate to form PRT063069. Both PRT062802 and PRT063069 were major circulating metabolites in human plasma with AUC of 34% and 24% that of betrixaban, respectively. PRT062802 was the only prominent metabolite detected in human urine and feces. In addition to hydrolysis metabolites, two CYP-mediated metabolites, O-desmethyl betrixaban (PRT058326) and N-desmethyl betrixaban (PRT054156), were observed in plasma at trace levels (AUC of each was <1% that of betrixaban). Trace levels of PRT058326 was also observed in urine and feces. Both PRT062802 and PRT063069 were inactive (IC50 for fXa inhibition >10 μM). PRT058326 and PRT054156 have an IC50 for fXa inhibition of approximately 5 nM compared to betrixaban Ki of 0.117 pM. Interaction of betrixaban with CYP enzymes was studied in vitro. CYP inhibition potential was evaluated in human liver microsomes with or without 30 minute pre-incubation of betrixaban. Selective probe substrates were used to monitor CYP activities, i.e. phenacetin for 1A2, tolbutamide for 2C9, S-mephenytoin for 2C19, dextromethorphan for 2D6, and testosterone and midazolam for 3A4. Betrixaban had IC50 > 80 μM for CYP1A2, 2C9, 2D6 and 3A4 for both competitive and time-dependent inhibition. IC50 for 2C19 were 43 and 88 μM for competitive and time-dependent inhibition, respectively. The CYP inhibition IC50's are much higher than the betrixaban therapeutic concentration of 50 nM. CYP induction by betrixaban was also studied using cryopreserved human hepatocytes (n=3). Betrixaban at 1, 10 and 25 μM were incubated in hepatocyte preparation for 48 hours. The activities for CYP1A2, CYP2C9, CYP2C19, and CYP3A4 were determined by measuring the formation of metabolites of the probe substrates similar to those used in the CYP inhibition study. CYP2C19 activities were not quantifiable in all three donors; therefore, induction for this CYP isoform could not be assessed. Betrixaban did not induce the activities of CYP1A2, CYP2C9, and CYP3A4. These results demonstrated that betrixaban was mainly excreted as the unchanged drug most likely via biliary secretion. Renal excretion and metabolism were minor elimination pathways. Betrixaban is unlikely to have drug-drug interactions with CYP-substrate, inducer, or inhibitor drugs. Disclosures: Hutchaleelaha: Portola pharmaceuticals: Employment. Ye:Portola Pharmaceuticals: Employment. Song:Portola Pharmaceuticals: Employment. Lorenz:Portola Pharmaceuticals: Employment. Gretler:Portola Pharmaceuticals: Equity Ownership. Lambing:Portola Pharmaceuticals: Employment.

The pharmacokinetics (PK) and pharmacodynamics (PD) of ABT-751 in children with recurrent neuroblastoma or other solid tumors

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 9557-9557
Author(s):  
E. Fox ◽  
B. C. Widemann ◽  
J. M. Maris ◽  
S. L. Cohn ◽  
H. Xiong ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Phase 1 ◽  
Parent Drug ◽  
Molar Ratio ◽  
Primary Metabolite ◽  
Drug Concentrations ◽  
Apparent Clearance ◽  
Major Route ◽  
Microtubule Formation ◽  
Sulfate Conjugate

9557 Background: ABT-751 is an orally administered agent that binds to the colchicine site on β-tubulin and blocks microtubule formation. We studied the PK and PD of ABT-751 and its sulfate and glucuronide conjugates in children enrolled on a phase 1 trial in solid tumors and a pilot study in neuroblastoma. Methods: Seventy-two children (2–18 yrs) received ABT-751 on a once, daily × 7d or daily × 21d schedule. Sixty had PK plasma sampling (53 sets analyzed), and 41 had a 24h urine collection after the first dose. Drug concentrations were quantified with a LC/MS/MS assay. Results: Median (range) plasma PK parameters are shown in the table . ABT-751 was rapidly absorbed (Tmax , 2h), and the Cmax and AUC0-8 increased in proportion to dose. The median molar ratio of the sulfate plasma AUC0-8 to glucuronide plasma AUC0-8 was 1.5. The median (range) percent of the administered dose excreted in urine as ABT-751, glucuronide, or sulfate conjugates was 0.09 (0–0.4)%, 10.2 (1.0–38.5)%, and 12.6 (2.3–50.9)%, respectively. The median ABT-751 AUC0-8 was higher in patients with dose-limiting toxicity (DLT) compared to those without DLT on the 7d (118 vs. 74.5 μg·h/mL; P=0.014) and 21d (73.8 vs 49.3 μg·h/mL; P=0.049) schedules. In 28 patients with neuroblastoma, the AUC0-8 did not correlate with time to progression. Apparent clearance (CL/F) did not correlate with age or gender. Conclusions: PK samples were obtained from 83% (60/72) of children enrolled. The ABT-751 AUC0-8 was dose proportional; inter- and intra-patient variability was low. Patients who experienced DLT had higher ABT-751 AUC0-8. The mean CL/F of ABT-751 was similar to that observed in adults (40 mL/min/m2) but did not correlate with age or gender. The sulfate conjugate was the primary metabolite in plasma and urine. Urinary excretion was not a major route of elimination of the parent drug. [Table: see text] No significant financial relationships to disclose.

Elucidation of the metabolic and elimination pathways of panobinostat (LBH589) using [14C]-panobinostat

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 2549-2549 ◽  
Author(s):  
S. Clive ◽  
M. M. Woo ◽  
M. Stewart ◽  
T. Nydam ◽  
S. Hirawat ◽  
...  
Keyword(s):  
Blood Plasma ◽  
Hydroxamic Acid ◽  
Oral Absorption ◽  
Total Radioactivity ◽  
Side Chain ◽  
Clinical Activity ◽  
Deacetylase Inhibitor ◽  
Radiometric Detection ◽  
Major Route ◽  
Clinically Significant

2549 Background: Panobinostat (PAN), a hydroxamic acid derivative, is a potent pan-deacetylase inhibitor, demonstrating anti-tumor activities in a wide variety of preclinical models and showing promising clinical activity. This study elucidates the metabolic and elimination pathways of PAN using [14C]-PAN. Methods: Four patients with advanced cancer received a single oral 20 mg dose of [14C]-PAN (50 μCi). Whole blood, plasma, urine, and feces were collected over 7 days. Total radioactivity was measured in blood, plasma, and excreta by liquid scintillation counting. PAN and its metabolite concentrations in plasma and excreta were measured by LC-MS/MS and HPLC with radiometric detection. Patients were monitored for safety. Results: The single PAN dose was well tolerated with no clinically significant laboratory or ECG abnormalities observed. PAN had a rapid oral absorption [median Tmax 0.8 h (range, 0.5–1 h)] and moderate elimination (median t1/2 31 h). The median t1/2 for blood and plasma radioactivity was 54 and 75 hours, respectively. Mass balance was achieved with ≥87% of the administered radioactivity being recovered in the excreta of all patients after 7 days. 44–77% and 29–51% of the dose was recovered in the feces and urine, respectively. Unchanged PAN accounted for ≤3% of the administered dose in the feces, suggesting good oral absorption. The most prominent metabolic pathways involved modifications of the hydroxamic acid (HA) side chain, to form an amide via reduction, carboxylic acid via either hydrolysis or one- and two-carbon (M1) shortening of the HA side chain. Oxygenation and glucuronidation were also observed. PAN accounted for ≤9% of the total radioactivity AUC. The most abundant circulating metabolites in plasma were the glucuronide of M1 (19%) and carbamoyl glucuronide of PAN (13%). At least 40 metabolites, many at trace levels, were observed circulating in plasma. Conclusions: PAN and its metabolites are equally excreted in the urine and feces. Elimination of PAN is primarily by metabolism via reduction, hydrolysis, oxidation and glucuronidation. The balanced elimination and absence of a single major route of PAN metabolism suggest that clinical drug-drug interactions are unlikely with PAN. [Table: see text]

scholarly journals Predicting when Biliary Excretion of Parent Drug is a Major Route of Elimination in Humans

2014 ◽  
Vol 16 (5) ◽  
pp. 1085-1096 ◽  
Author(s):  
Chelsea M. Hosey ◽  
Fabio Broccatelli ◽  
Leslie Z. Benet
Keyword(s):  
Biliary Excretion ◽  
Parent Drug ◽  
Major Route
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