Comparison of Canine and Human Physiological Factors: Understanding Interspecies Differences that Impact Drug Pharmacokinetics

Liver transporters play an important role in the pharmacokinetics and disposition of pharmaceuticals, environmental contaminants, and endogenous compounds. Among them, the family of ATP-Binding Cassette (ABC) transporters is the most important due to its role in the transport of endo- and xenobiotics. The ABCC sub-family is the largest one, consisting of 13 members that include the cystic fibrosis conductance regulator (CFTR/ABCC7); the sulfonylurea receptors (SUR1/ABCC8 and SUR2/ABCC9) and the multidrug resistanceassociated proteins (MRPs). The MRP-related proteins can collectively confer resistance to natural, synthetic drugs and their conjugated metabolites, including platinum-containing compounds, folate anti-metabolites, nucleoside and nucleotide analogs, among others. MRPs can be also catalogued into "long" (MRP1/ABCC1, -2/C2, -3/C3, -6/C6, and -7/C10) and "short" (MRP4/C4, -5/C5, -8/C11, -9/C12, and -10/C13) categories. While MRP2/ABCC2 is expressed in the canalicular pole of hepatocytes, all others are located in the basolateral membrane. In this review, we summarize information from studies examining the changes in expression and regulation of the basolateral hepatic transporter MPR3/ABCC3 by xenobiotics and during various pathophysiological conditions. We also focus, primarily, on the consequences of such changes in the pharmacokinetic, pharmacodynamic and/or toxicity of different drugs of clinical use transported by MRP3.

Download Full-text

A Review of the Physiological Factors Associated with Alcohol Hangover

Current Drug Abuse Reviews ◽

10.2174/1874473710666170207152933 ◽

2017 ◽

Vol 9 (2) ◽

pp. 93-98 ◽

Cited By ~ 17

Author(s):

Celeste T. Tipple ◽

Sarah Benson ◽

Andrew Scholey

Keyword(s):

Physiological Factors ◽

Factors Associated ◽

Alcohol Hangover

Download Full-text

Differential effects of the blood pressure state on pulse rate variability and heart rate variability in critically ill patients

npj Digital Medicine ◽

10.1038/s41746-021-00447-y ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Elisa Mejía-Mejía ◽

James M. May ◽

Mohamed Elgendi ◽

Panayiotis A. Kyriacou

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Heart Rate Variability ◽

Pulse Rate ◽

Pulse Transit Time ◽

Pulse Rate Variability ◽

Physiological Factors ◽

Ecg Signals ◽

Non Invasive ◽

Electrocardiogram Ecg

AbstractHeart rate variability (HRV) utilizes the electrocardiogram (ECG) and has been widely studied as a non-invasive indicator of cardiac autonomic activity. Pulse rate variability (PRV) utilizes photoplethysmography (PPG) and recently has been used as a surrogate for HRV. Several studies have found that PRV is not entirely valid as an estimation of HRV and that several physiological factors, including the pulse transit time (PTT) and blood pressure (BP) changes, may affect PRV differently than HRV. This study aimed to assess the relationship between PRV and HRV under different BP states: hypotension, normotension, and hypertension. Using the MIMIC III database, 5 min segments of PPG and ECG signals were used to extract PRV and HRV, respectively. Several time-domain, frequency-domain, and nonlinear indices were obtained from these signals. Bland–Altman analysis, correlation analysis, and Friedman rank sum tests were used to compare HRV and PRV in each state, and PRV and HRV indices were compared among BP states using Kruskal–Wallis tests. The findings indicated that there were differences between PRV and HRV, especially in short-term and nonlinear indices, and although PRV and HRV were altered in a similar manner when there was a change in BP, PRV seemed to be more sensitive to these changes.

Download Full-text

Interplay among Antioxidant System, Hormone Profile and Carbohydrate Metabolism during Bud Dormancy Breaking in a High-Chill Peach Variety

Antioxidants ◽

10.3390/antiox10040560 ◽

2021 ◽

Vol 10 (4) ◽

pp. 560

Author(s):

José A. Hernández ◽

Pedro Díaz-Vivancos ◽

José Ramón Acosta-Motos ◽

Nuria Alburquerque ◽

Domingo Martínez ◽

...

Keyword(s):

Starch Content ◽

Sugar Metabolism ◽

Bud Dormancy ◽

Dormancy Breaking ◽

Prunus Species ◽

Physiological Factors ◽

Antioxidant Metabolism ◽

Hormone Profile ◽

Aba Content ◽

Gas Ratio

(1) Background: Prunus species have the ability to suspend (induce dormancy) and restart growth, in an intricate process in which environmental and physiological factors interact. (2) Methods: In this work, we studied the evolution of sugars, antioxidant metabolism, and abscisic acid (ABA) and gibberellins (GAs) levels during bud dormancy evolution in a high-chill peach variety, grown for two seasons in two different geographical areas with different annual media temperature, a cold (CA) and a temperate area (TA). (3) Results: In both areas, starch content reached a peak at ecodormancy, and then decreased at dormancy release (DR). Sorbitol and sucrose declined at DR, mainly in the CA. In contrast, glucose and fructose levels progressively rose until DR. A decline in ascorbate peroxidase, dehydroascorbate reductase, superoxide dismutase and catalase activities occurred in both seasons at DR. Moreover, the H2O2-sensitive SOD isoenzymes, Fe-SOD and Cu,Zn-SOD, and two novel peroxidase isoenzymes, were detected. Overall, these results suggest the occurrence of a controlled oxidative stress during DR. GA7 was the major bioactive GA in both areas, the evolution of its levels being different between seasons and areas. In contrast, ABA content decreased during the dormancy period in both areas, resulting in a reduction in the ABA/total GAs ratio, being more evident in the CA. (4) Conclusion: A possible interaction sugars-hormones-ROS could take place in high-chill peach buds, favoring the DR process, suggesting that, in addition to sugar metabolism, redox interactions can govern bud DR, regardless of chilling requirements.

Download Full-text