In vivo pharmacokinetic study and oral glucose tolerance test of sulfoxide analogs of GPR40 agonist TAK ‐875

2020 ◽  
Vol 81 (6) ◽  
pp. 708-715
Author(s):  
Yugang Yan ◽  
Qifu Xu ◽  
Chunlong Zhao ◽  
Hang Dong ◽  
Wenfang Xu ◽  
...  
Author(s):  
Bungorn Sripanidkulchai ◽  
Catheleeya Mekjaruskul ◽  
Rosawan Areemit ◽  
Areewan Cheawchanwattana ◽  
Jiraporn Sithithaworn

Kaempferia parviflora Wall. ex Baker (KP), Krachaidam in Thai or Thai ginseng, is an herbal medicine that has many potential pharmacological effects. This study focused on the oral glucose tolerance test and pharmacokinetic study in healthy volunteers administered with KP extract (90 and 180 mg/day, placebo). The oral glucose tolerance tests were performed at baselines and 28-days of administration. The pharmacokinetics were determined after a single dose administration of the tested products using 3,5,7,3,4-pentamethoxyflavone (PMF) and 5,7,4-trimethoxylfavone (TMF) as markers. The results showed that glucose metabolism via oral glucose tolerance test was not affected by KP extract. The results of pharmacokinetics study revealed that only TMF and PMF, but not DMF levels could be detected in human blood. The given doses of KP extract at 90 and 180 mg/day showed a linear dose-relationship of blood PMF concentration whereas blood TMF was detected only at high given dose (180 mg/day). The half-lives of PMF and TMF were 2–3 h. The Cmax, AUC and Tmax values of PMF and TMF estimated for the 180 mg/day dose were 85.3711.31, 73.2329.93 mg/ml; 291.8948.23, 412.20203.69 mg.h/ml; and 3.890.37, 4.500.96 h, respectively. PMF was quickly eliminated with higher Ke and Cl than TMF at the dose of 180 mg/day of KP extract. In conclusion, the results demonstrated that KP extract had no effect on glucose tolerance test. In addition, this is the first demonstration of the pharmacokinetic parameters of methoxyflavones of KP extract in healthy volunteers in a phase I study in drug development. The data suggest the safety of the KP extract and will be of benefit for further clinical trials using KP extract as food and sport supplements as well as a drug in health product development.


2021 ◽  
Vol 12 ◽  
Author(s):  
Rohit Sharma ◽  
Rajesh Bolleddu ◽  
Jayanta K. Maji ◽  
Galib Ruknuddin ◽  
Pradeep K. Prajapati

Guduchi (Tinospora cordifolia [Willd.] Miers) is a flagship rejuvenating herb of Ayurveda with reported anti-diabetic potential. In the present study, different dosage forms of Guduchi stem (growing on neem tree) were developed by adopting Ayurvedic pharmaceutical process of Bhavana (levigation). Guduchi Churna (GC) was subjected to 07 times Bhavana separately with its own extracted juice, decoction and potable water, and dosage forms namely Svarasa Bhavita Guduchi Churna (SBGC), Kwatha Bhavita Guduchi Churna (KBGC), and Jala Bhavita Guduchi Churna (JBGC) were prepared. The present study was aimed to evaluate the role of Bhavana on the potentiation of therapeutic properties of Guduchi. Sequential solvent extracts (5, 10, 15 and 25%) of GC, SBGC, KBGC and JBGC were prepared in different solvents [phosphate buffer, hexane, dichloromethane (DCM), chloroform] and screened for the α-amylase and α-glucosidase inhibitory activity. The results revealed that phosphate buffer and DCM extracts of SBGC exhibited strong α-amylase inhibitory potential (>80% inhibition at 25% concentration) followed by KBGC, JBGC and GC with reference to the standard acarbose. In α-glucosidase inhibitory activity, maximum inhibition was observed in DCM and chloroform extracts of SBGC (>85% inhibition at 25% concentration), followed by KBGC (>80% inhibition at 25% concentration), JBGC and GC. In vivo anti-hyperglycemic studies were carried out by oral glucose tolerance test in Swiss albino mice. Test drugs (JBGC, KBGC, SBGC) treated groups showed marginal decrease of blood glucose levels in normo glycemic mice. However, the blood glucose level in test drug JBGC, KBGC and SBGC treated groups was still within normal range in overnight fasted mice. In oral glucose tolerance test, among all dosage forms SBGC (51.08%) produced pronounced anti-hyperglycemic effect followed by KBGC (42.57%) at a dose of 520 mg/kg. The GC, JBGC, KBGC and SBGC samples were also standardized using berberine (a well established anti-diabetic compound) as a marker compound by HPTLC fingerprint analysis. Findings of the present study indicate that SBGC and KBGC can be used in the treatment of diabetes mellitus and gives supporting evidence to Ayurvedic claims that the Bhavana process has pharmaceutico-therapeutic significance in Ayurvedic drug development.


Nutrients ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 1176
Author(s):  
Bungorn Sripanidkulchai ◽  
Catheleeya Mekjaruskul ◽  
Rosawan Areemit ◽  
Areewan Cheawchanwattana ◽  
Jiraporn Sithithaworn

Kaempferia parviflora Wall. ex Baker (KP), Krachaidam in Thai or Thai ginseng, is a herbal medicine that has many potential pharmacological effects. The effect of KP extract on blood glucose level in rodent was reported. This study focused on the oral glucose tolerance test and pharmacokinetic study in healthy volunteers administered with KP extract (90 and 180 mg/day, placebo). The oral glucose tolerance tests were performed at baselines and 28-days of administration. The pharmacokinetics were determined after a single dose administration of the tested products using 3,5,7,3′,4′-pentamethoxyflavone (PMF) and 5,7,4′-trimethoxylflavone (TMF) as markers. The results showed that glucose metabolism via oral glucose tolerance test was not affected by KP extract. Blood glucose levels of volunteers at 120 min after glucose loading were able to be returned to initial levels in placebo, KP 90 mg/day, and KP 180 mg/day groups both at baseline and 28-days of administration. The results of the pharmacokinetic study revealed that only TMF and PMF, but not 5,7-dimethoxyflavone (DMF) levels could be detected in human blood. The given doses of KP extract at 90 and 180 mg/day showed a linear dose-relationship of blood PMF concentration whereas blood TMF was detected only at high given dose (180 mg/day). The half-lives of PMF and TMF were 2–3 h. The maximum concentration (Cmax), area under the curve of blood concentration and time (AUC), and time to maximum concentration (Tmax) values of PMF and TMF estimated for the 180 mg/day dose were 71.2 ± 11.3, 63.0 ± 18.0 ng/mL; 291.9 ± 48.2, 412.2 ± 203.7 ng∙h/mL; and 4.02 ± 0.37, 6.03 ± 0.96 h, respectively. PMF was quickly eliminated with higher Ke and Cl than TMF at the dose of 180 mg/day of KP extract. In conclusion, the results demonstrated that KP extract had no effect on the glucose tolerance test. In addition, this is the first demonstration of the pharmacokinetic parameters of methoxyflavones of KP extract in healthy volunteers. The data suggest the safety of the KP extract and will be of benefit for further clinical trials using KP extract as food and sport supplements as well as a drug in health product development.


2005 ◽  
Vol 11 ◽  
pp. 28
Author(s):  
Fanny Rodriguez Vallejo ◽  
Juan Manuel Rios Torres ◽  
Francisco J. Gomez-Pérez ◽  
Juan A. Rull Rodrigo ◽  
Bernardo Pérez Enriquez

2016 ◽  
Author(s):  
Zivkovic Teodora Beljic ◽  
Biljana Jojic ◽  
Jelic Marina Andjelic ◽  
Goran Loncar ◽  
Aleksandar Davidovic ◽  
...  

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