DoseCal: a virtual calculator for dosage conversion between human and different animal species

Janhavi, P.; Divyashree, S.; Sanjailal, K P; Muthukumar, S. P.

doi:10.1080/13813455.2019.1687523

Cited by 45 publications

(34 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A randomized human trial confirmed that oral administration of 2 g or 4 g of γ-GC could effectively increase lymphocyte GSH levels [21]. The dose conversion from humans to mice is multiplied by 12 [43]. Therefore, we planned to assess γ-GC concentrations of 300 mg/kg and 600 mg/kg.…”

Section: Discussionmentioning

confidence: 99%

γ‐Glutamylcysteine Alleviates Ischemic Stroke‐Induced Neuronal Apoptosis by Inhibiting ROS‐Mediated Endoplasmic Reticulum Stress

Xia

et al. 2021

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Ischemic stroke is a severe and acute neurological disorder with limited therapeutic strategies currently available. Oxidative stress is one of the critical pathological factors in ischemia/reperfusion injury, and high levels of reactive oxygen species (ROS) may drive neuronal apoptosis. Rescuing neurons in the penumbra is a potential way to recover from ischemic stroke. Endogenous levels of the potent ROS quencher glutathione (GSH) decrease significantly after cerebral ischemia. Here, we aimed to investigate the neuroprotective effects of γ-glutamylcysteine (γ-GC), an immediate precursor of GSH, on neuronal apoptosis and brain injury during ischemic stroke. Middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation/reoxygenation (OGD/R) were used to mimic cerebral ischemia in mice, neuronal cell lines, and primary neurons. Our data indicated that exogenous γ-GC treatment mitigated oxidative stress, as indicated by upregulated GSH and decreased ROS levels. In addition, γ-GC attenuated ischemia/reperfusion-induced neuronal apoptosis and brain injury in vivo and in vitro. Furthermore, transcriptomics approaches and subsequent validation studies revealed that γ-GC attenuated penumbra neuronal apoptosis by inhibiting the activation of protein kinase R-like endoplasmic reticulum kinase (PERK) and inositol-requiring enzyme 1α (IRE1α) in the endoplasmic reticulum (ER) stress signaling pathway in OGD/R-treated cells and ischemic brain tissues. To the best of our knowledge, this study is the first to report that γ-GC attenuates ischemia-induced neuronal apoptosis by suppressing ROS-mediated ER stress. γ-GC may be a promising therapeutic agent for ischemic stroke.

show abstract

Section: Discussionmentioning

confidence: 99%

γ‐Glutamylcysteine Alleviates Ischemic Stroke‐Induced Neuronal Apoptosis by Inhibiting ROS‐Mediated Endoplasmic Reticulum Stress

Xia

et al. 2021

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

show abstract

“…The doses were calculated using DoseCal. 46 The locomotor activities of the rats were recorded for 2 days (before and after MWM), i.e., 6th and 13th days. The MWM test was performed for 5 days (8th–12th day).…”

Section: Methodsmentioning

confidence: 99%

Neuroprotective Effect of Spice Oleoresins on Memory and Cognitive Impairment Associated with Scopolamine-Induced Alzheimer’s Disease in Rats

et al. 2020

View full text Add to dashboard Cite

Oleoresins are a mixture of volatile and nonvolatile components of concentrated forms of wholesome products. Even though there are several reports on the effect of spice or spice components on Alzheimer’s disease, there are no studies on the effect of spice oleoresins. Hence, this study investigates the effect of pepper, chili, and turmeric oleoresins in Alzheimer’s type of cognitive impairment in the rat model. The animals were grouped into six groups with six animals in each. They were (i) normal, (ii) scopolamine, (iii) scopolamine + pepper oleoresin, (iv) scopolamine + turmeric oleoresin, (v) scopolamine + chili oleoresin and (vi) scopolamine + donepezil for 13 days. Learning memory and acquisition memory were evaluated by a Morris water maze, and the locomotor activity was assessed by an actophotometer. Biochemical parameters such as AChE, malondialdehyde, reduced glutathione, glutathione peroxidase, superoxide dismutase, and catalase were studied. The brain histology was also studied. The scopolamine treatment significantly (P < 0.05) elevated the locomotor activity and escape latency time and reduced the time spent in the target quadrant, which was reversed in the case of the oleoresin treatment. Scopolamine-mediated changes in AChE, malondialdehyde, reduced glutathione, glutathione peroxidase, superoxide dismutase, and catalase were improved after the treatment with oleoresins. Among the three oleoresins, chili oleoresin were the most effective in behavioral activity, brain biomarkers, and recovery of antioxidant capacities when compared to the drug treatment. Chili and pepper oleoresins improved the protection against hippocampal damage. These oleoresins can be potent preventive/therapeutic agents against Alzheimer’s disease. This study confirms the effect of spice oleoresins in Alzheimer’s disease condition.

show abstract

“…Using the PKSolver, these data were used for calculation of PK parameters for a noncompartmental model including areas under the plasma drug concentration–time curve from time zero to 24 h (AUC 0–24 ) and from time zero to infinity (AUC 0–inf ) 18 . Conversions of animal doses to human equivalent doses (HEDs) and the yet only human dose to animal equivalent doses were based on allometric scaling with normalization to body surface area using the equation: HED = Animal dose x (Animal weight/Human weight) (1–0.67) , where HED and animal dose are in mg/kg, animal and human weights are in kg and 0.67 is the body surface‐based scaling factor 19–21 . Although this scaling factor is well‐established for estimation of HEDs, 0.74 and 0.75 may perform better as factors for allometric‐based interspecies drug dose conversion 22,23 .…”

Section: Data Sources and Calculationsmentioning

confidence: 99%

Nucleoside analog GS‐441524: pharmacokinetics in different species, safety, and potential effectiveness against Covid‐19

Rasmussen

Thomsen

Hansen

2022

Pharmacology Res & Perspec

View full text Add to dashboard Cite

GS‐441524, the parent nucleoside of remdesivir, has been proposed to be effective against Covid‐19 based on in vitro studies and studies in animals. However, randomized clinical trials of the agent to treat Covid‐19 have not been conducted. Here, we evaluated GS‐441524 for Covid‐19 treatment based on studies reporting pharmacokinetic parameters of the agent in mice, rats, cats, dogs, monkeys, and the single individual in the first‐in‐human trial supplemented with information about its activity against severe acute respiratory syndrome coronavirus 2 and safety. A dosing interval of 8 h was considered clinically relevant and used to calculate steady‐state plasma concentrations of GS‐441524. These ranged from 0.27 to 234.41 μM, reflecting differences in species, doses, and administration routes. Fifty percent maximal inhibitory concentrations of GS‐441524 against severe acute respiratory syndrome coronavirus 2 ranged from 0.08 μM to above 10 μM with a median of 0.87 μM whereas concentrations required to produce 90% of the maximal inhibition of the virus varied from 0.18 µM to more than 20 µM with a median of 1.42 µM in the collected data. Most of these concentrations were substantially lower than the calculated steady‐state plasma concentrations of the agent. Plasma exposures to orally administered GS‐441524, calculated after normalization of doses, were larger for dogs, mice, and rats than cynomolgus monkeys and humans, probably reflecting interspecies differences in oral uptake with reported oral bioavailabilities below 8.0% in cynomolgus monkeys and values as high as 92% in dogs. Reported oral bioavailabilities in rodents ranged from 12% to 57%. Using different presumptions, we estimated human oral bioavailability of GS‐441524 at 13% and 20%. Importantly, doses of GS‐441524 lower than the 13 mg/kg dose used in the first‐in‐human trial may be effective against Covid‐19. Also, GS‐441524 appears to be well‐tolerated. In conclusion, GS‐441524 has potential for oral treatment of Covid‐19.

show abstract

DoseCal: a virtual calculator for dosage conversion between human and different animal species

Cited by 45 publications

References 8 publications

γ‐Glutamylcysteine Alleviates Ischemic Stroke‐Induced Neuronal Apoptosis by Inhibiting ROS‐Mediated Endoplasmic Reticulum Stress

γ‐Glutamylcysteine Alleviates Ischemic Stroke‐Induced Neuronal Apoptosis by Inhibiting ROS‐Mediated Endoplasmic Reticulum Stress

Neuroprotective Effect of Spice Oleoresins on Memory and Cognitive Impairment Associated with Scopolamine-Induced Alzheimer’s Disease in Rats

Nucleoside analog GS‐441524: pharmacokinetics in different species, safety, and potential effectiveness against Covid‐19

Contact Info

Product

Resources

About